| 1. |
Comparative Analysis of Pharmacokinetics and Metabolites of Three Main Terpenoids before and after Compatibility of Frankincense and Myrrh in Rats by UHPLC-MS.
Fan RY, Gao RM, Li JS, Su SL, Shang EX, Qian DW, Duan JA
BACKGROUND: 3-acetyl-11-keto-beta-boswellic acid (AKBA) and 11-keto-boswellic acid (KBA) are the main active components of frankincense as pentacyclic triterpenoids, which are designated by the European Pharmacopoeia 8.0 as the quality standard for the evaluation of Indian frankincense, 2-methoxy-8,12-epoxygermacra- 1(10),7,11-trien-6-one (MCS134) is a non-volatile sesquiterpene compound in myrrh.
OBJECTIVE: In this paper, the absorption pharmacokinetics and metabolites of AKBA, KBA and MCS134 after frankincense, myrrh and their compatibility were analyzed, elaborated their absorption and metabolism mechanism and provided the ideas for the research on the bioactive components of frankincense and myrrh compatibility .
METHODS: The area under the blood concentration time curve (AUC), half-life (t1/2) and drug clearance (CL) of AKBA, KBA and MCS134 in rats were analyzed by LC-TQ / MS. The metabolites of AKBA, KBA and MCS134 in rats were analyzed by ultra-high pressure liquid chromatography with a linear ion trap-high resolution Orbitrap mass spectrometry system (UHPLC-LTQ-Orbitrap-MS).
RESULTS: The results showed that AKBA, KBA and MCS134 reached the maximum plasma concentration at about 2 h, 2 h and 15 min, respectively. AUC0-t and t1/2 of the three components increased in varying degrees after compatibility, and the clearance/ bioavailability (CL/F) decreased. AKBA, KBA and MCS134 were metabolized in phase I and phase II in rats, and there represented differences before and after compatibility.
CONCLUSION: After the compatibility of frankincense and myrrh, the absorption of effective components was improved to some extent, and there were some differences in the metabolites in rats. The results provide ideas for elucidating the effect mechanism of frankincense and myrrh.
Curr Drug Metab. 2023;24(6):434-447.
PMID: 37559536 [PubMed - as supplied by publisher]
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| 2. |
[Comparison of in vivo plasma pharmacokinetics and urine excretion of main components in Xihuang Formula in rats with precancerous lesions of breast cancer].
Xie JX, Zhang YJ, Huang PW, Zhang YT, Wang Z, Feng NP
The UPLC-MS/MS was established for the determination of acetyl-11-keto-beta-boswellic acid(AKBA) and β-boswellic acid(β-BA), the main active components of Olibanum and Myrrha extracts in Xihuang Formula, in rat plasma and urine. The effects of compatibility on the pharmacokinetic behaviors of AKBA and β-BA in rats were investigated, and the differences in pharmacokinetic behaviors between healthy rats and rats with precancerous lesions of breast cancer were compared. The results showed that compared with RM-NH and RM-SH groups, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05 or P<0.01), T_(max) decreased(P<0.05 or P<0.01), and C_(max) increased(P<0.01) after compatibility. The trends of AKBA and β-BA were the same. Compared with RM-SH group, the T_(max) decreased(P<0.05), C_(max) increased(P<0.01), and the absorption rate increased in the normal group of Xihuang Formula. The results of urinary excretion showed that there was a decreasing trend in the urinary excretion rate and total urinary excretion of β-BA and AKBA after compatibility, but there was no statistical difference. Compared with normal group of Xihuang Formula, the AUC_(0-t) and AUC_(0-∞) of β-BA increased(P<0.05), T_(max) increased(P<0.05), and the clearance rate decreased in the breast precancerous lesion group. AUC_(0-t) and AUC_(0-∞) of AKBA showed an increasing trend, the in vivo retention time was prolonged, and the clearance rate was reduced, but there was no significant difference compared with the normal group. The cumulative urinary excretion and urinary excretion rate of β-BA and AKBA decreased under pathological conditions, indicating that pathological conditions could affect the in vivo process of β-BA and AKBA, and reduce their excretion in the form of prototype drugs, showing different pharmacokine-tic characteristics from normal physiological conditions. In this study, UPLC-MS/MS analysis method was established, which was sui-table for in vivo pharmacokinetic analysis of β-BA and AKBA. This study laid a foundation for the development of new dosage forms of Xihuang Formula.
Zhongguo Zhong Yao Za Zhi. 2023 Mar;48(6):1642-1651.
PMID: 37005852 [PubMed - indexed for MEDLINE]
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| 3. |
Phase III randomized clinical trial of BV-4051, an Ayurvedic polyherbal formulation in moderate SARS-CoV-2 infections and its impact on inflammatory biomarkers.
Chitre D, Nadkarni S, Jagtap N, Tulle R, Gitte A, Rahate P, Chaskar S, Dey D
SARS-CoV-2 virus and its variants continue to be a challenge inspite of widespread vaccination and preventive measures. We hypothesized an oral, safe polyherbal formulation with antiinflammatory properties may improve the clinical outcome of this disease. BV-4051, a formulation from four Ayurvedic plants namely Ashwagandha, Boswellia, Ginger and Turmeric was used for the treatment of hospitalized moderate COVID-19 patients along with standard of care (SOC). Patients were randomly assigned to receive BV-4051 or placebo tablets for 14 days, at four sites in India during late 2020 to early 2021. Among 208 randomized subjects, 175 completed the study. In BV-4051 group the mean reduction in duration of illness (p = 0.036), alleviation and severity scores of several symptoms like fever, cough, smell, and taste disorders were statistically significant (p ≤ 0.05). A sub-set analysis of subjects treated with or without Remdesivir as SOC showed mean reduction in duration of illness in BV-4051 (p = 0.030), and severity scores (p ≤ 0.05). Mean difference in Interleukin-6 was statistically significant (p = 0.042) on BV-4051 without Remdesivir. BV-4051 may reduce duration of illness, symptoms severity, Interleukin-6, and prevent the incidence of COVID-19 complications. It may have an adjunctive effect with other SOC. Larger extensive clinical testing may give a better understanding of its effect.
Phytother Res. 2023 Apr;37(4):1232-1241.
PMID: 36419388 [PubMed - indexed for MEDLINE]
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| 4. |
Analysis of the pharmacodynamic difference between Xiaojin Pills taken with Chinese Baijiu and water based on serum pharmacochemistry and pharmacokinetics.
Song J, Liao W, Deng X, Zhang D, Lin J, Xu R, Han L
ETHNOPHARMACOLOGICAL RELEVANCE: Xiaojin Pills (XJPs), which has the function of dissipating knots and dispersing swelling, removing blood stasis, and relieving pain, is a classic prescription for the treatment of mammary glands hyperplasia. It is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinics. Previous studies have shown that the efficacy of XJPs "taken orally after soaked with Chinese Baijiu" in tradition was significantly better than that of taking it orally with water in modern in terms of activating the blood, anti-inflammation, analgesia, anti-mammary gland hyperplasia, anti-breast cancer and its metastasis in vitro and in vivo, especially under low-dose conditions. However, the material basis for the difference in efficacy between XJP&B and XJP&W is still unclear.
AIM OF THE STUDY: To analyze the material basis of the significant difference in efficacy between XJP&B and XJP&W from the perspective of serum pharmacochemistry and pharmacokinetics, and clarified the scientific connotation of XJPs "taken orally after soaked with Chinese Baijiu".
MATERIALS AND METHODS: Ultra-high performance liquid chromatography-mass spectrometry combined with a multivariate statistical analysis method were used to screen the differential components in the Chinese Baijiu extract and the water extract of XJPs and the corresponding residues, so as to clarify the differential components between XJP&B and XJP&W in vitro. The migrating components in the blood after XJP&B and XJP&W were characterized by serum pharmacochemical methods, in order to clarify the differential components in rats. The pharmacokinetic parameters of the representative components absorbed into the blood were compared between XJP&B and XJP&W by the pharmacokinetics study method, in order to determine the dynamic changes of the representative components in rats.
RESULTS: The identification results of different components in vitro showed that there were 34 and 12 different compounds between the Chinese Baijiu extract and water extract of XJPs, and the residues after Chinese Baijiu extraction and water extraction, respectively. The content of different components such as arachidonic acid, ursolic acid, 3-acetyl-11-keto-β-boswellic acid, 2α-hydroxyursolic acid, and oleanolic acid was higher in the Chinese Baijiu extract, which was more than twice the content in the water extract. The results of the serum pharmacochemistry study indicated that 42 prototype components were identified in the serum of rats after XJP&B and XJP&W, including organic acids, alkaloids, steroids, and terpenoids. And XJP&B increased the absorption of the prototype components of organic acids in XJPs into the blood. The pharmacokinetic study results of representative components demonstrated that the mean plasma concentration-time profile and pharmacokinetic parameters of muscone, aconitine, and 3-acetyl-11-keto-β-boswellic acid were significantly different between XJP&B and XJP&W. Compared with XJP&W, the C and AUC of muscone and aconitine in XJP&B were higher, and the T and MRT of 3-acetyl-11-keto-β-boswellic acid in XJP&B were relatively longer.
CONCLUSION: This research proved that "taking XJPs orally after being soaked with Chinese Baijiu" can increase the dissolution and absorption of active ingredients in XJPs, increase the plasma concentration and content of representative ingredients, and prolong its action time, thus enhancing the biological activity of XJPs in vitro and in vivo. To a certain extent, this study revealed the material basis of the significantly better efficacy of XJP&B than XJP&W and clarified the scientific connotation of XJPs "taken orally after soaked with Chinese Baijiu", which can provide a theoretical basis for the optimization of XJPs' clinical administration method.
J Ethnopharmacol. 2023 Jan;300():115723.
PMID: 36115600 [PubMed - indexed for MEDLINE]
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| 5. |
Assessment of depth of penetration and antibiofilm properties of Boswellia sacra compared with calcium hydroxide intracanal medicament (in vitro study).
El-Essawy RH, Al-Ashry S, Sabet NE, Ghobashy AM
Successful endodontic treatment requires advanced materials to eliminate biofilm This study aims to assess the penetration depth and the effectiveness of Boswellia sacra as a novel intracanal medicament compared with calcium hydroxide against Enterococcus faecalis biofilm. 60 single-rooted teeth were decoronated, prepared and sterilised. Fifty teeth were contaminated with a culture of E. faecalis (ATCC 19433) for 21 days. Two teeth were used to confirm the biofilm using scanning electron microscope. For colony-forming unit (CFU), 40 samples were divided into one control group (calcium hydroxide) and the other experimental group (B. sacra). Each group was divided into two subgroups to be tested at 3 and 7 days. The minimum inhibitory concentration (MIC) of B. sacra was determined, and the B. sacra's ethanolic extract medicament was prepared. Eight discs divided into groups similar to CFU were used to evaluate live/dead bacteria using confocal laser scanning microscopy (CLSM). Ten teeth were selected for penetration depth using CLSM. The intracanal medicaments were mixed with 0.1% rhodamine B. were inserted into the root canals 0.2 slices were dissected and viewed under CLSM. The MIC of B. sacra was 1.25 mg/ml. The CFU evaluation proved that B. sacra are more effective than calcium hydroxide in the 3 days groups. However, it was statistically insignificant compared with calcium hydroxide after 7 days. The depth of penetration of B. sacra exceeds that of calcium hydroxide. B. sacra is an effective intracanal medicament.
Aust Endod J. 2023 Aug;49(2):295-301.
PMID: 36004503 [PubMed - indexed for MEDLINE]
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| 6. |
Co-encapsulation of curcumin and boswellic acids in chitosan-coated niosome: an digestion study.
Salehi S, Nourbakhsh MS, Yousefpour M, Rajabzadeh G, Sahab-Negah S
In this study, chitosan-coated niosome (ChN) was utilised for bioavailability enhancement of curcumin (Cn) and boswellic acids (BAs). The bare niosome (BN) was prepared by the heating method and optimised by using the mixture design procedure. Physicochemical stability, as well as the in vitro release, and bioavailability of Cn and BAs in BN and ChN were studied. The optimised BN had a mean diameter of 70.00 ± 0.21 nm and surface charge of -31.00 ± 0.25 mv, which changed to 60.01 ± 0.20 nm and +40.00 ± 0, respectively, in ChN. digestion study revealed chitosan layer augmented the bioavailability of Cn and BAs to 79.02 ± 0.13 and 81 ± 0.10, respectively. The chitosan layer obviously improved the physical stability of Cn and BA in the niosome vehicle, by means of vesicle size, zeta potential, and encapsulation efficiency. The ChN was considered to be promising delivery system for increasing the bioavailability of Cn and BAs.
J Microencapsul. 2022 May;39(3):226-238.
PMID: 35384786 [PubMed - indexed for MEDLINE]
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| 7. |
Bioavailability, anti-inflammatory and anti-arthritic effect of Acetyl Keto Boswellic acid and its combination with methotrexate in an arthritic animal model.
Banji D, Banji OJF, Rashida S, Alshahrani S, Alqahtani SS
ETHNOPHARMACOLOGICAL RELEVANCE: Rheumatoid arthritis is one of the most common disabling chronic progressive autoimmune diseases affecting the adult world population. Boswellia serrata has been a known anti-inflammatory agent since ancient times. Therefore, research on Boswellia extract based on Acetyl Keto Boswellic Acid (AKBA) content evaluating its efficacy and safety is necessary. The study aimed to find a suitable Boswellia extract rich in AKBA to evaluate its bioavailability, anti-inflammatory, and anti-arthritic effect. In addition, the synergistic action of AKBA extract with methotrexate (MTX) was also assessed on an animal model.
MATERIALS AND METHODS: Oral bioavailability of AKBA and the anti-inflammatory activity of 10% AKBA (5, 10, 20, 40 mg/kg b.w) was assessed and compared with 2% AKBA (40 mg/kg) and diclofenac (10 mg/kg). The effect of 10% AKBA at 20 mg/kg and 40 mg/kg was evaluated in the FCA induced arthritis animal model alone and combined with methotrexate (MTX) at 2 mg/kg b.w. Subplantar injection of FCA produced edema within a few hours with progressive arthritis by the 9th day after injection. All the treatments were initiated from the 10th day until the 45th day. Oral administration of 10% AKBA was done daily and MTX by intraperitoneal route once a week from day 10 to day 45. Paw volume, erythrocyte sedimentation rate (ESR), serum glutamic oxaloacetic transaminase (SGOT), serum glutamic pyruvic transaminase (SGPT), alkaline phosphatase (ALP), total bilirubin, oxidative markers (superoxide dismutase (SOD) levels, malondialdehyde (MDA), total proteins and liver histopathology were examined.
RESULTS: 10% AKBA provided 8.48-fold, 24.22-fold, 47.36-fold, and 110.53-fold higher AUC (0-α) of AKBA at 5 mg/kg, 10 mg/kg, 20 mg/kg and 40 mg/kg, respectively compared to 2% AKBA at 40 mg/kg. Percentage paw edema inhibition of 10% AKBA at 20 mg/kg and 40 mg/kg were significantly higher than 2% regular AKBA (40 mg/kg) and diclofenac (10 mg/kg). 10% AKBA at a dose of 20 and 40 mg/kg significantly reduced ESR compared with FCA treated group. A combination of methotrexate with 10% AKBA showed the highest reduction in ESR. 10% AKBA at both dose levels significantly reduced hepatic marker enzymes and total bilirubin levels. Treatment with 10% AKBA showed a significant increase in total proteins, antioxidant enzymes and a decrease in malondialdehyde levels. Similarly, 10% AKBA protected the hepatocytes compared with the FCA and FCA + MTX treated group. 10% AKBA was capable of significantly minimizing FCA and FCA + MTX induced changes.
CONCLUSION: Anti-inflammatory activity of AKBA due to inhibition of lipoxygenase (LOX) enzymes supports the use of AKBA in inflammatory disorders. Combination therapy of 10% AKBA with MTX is effective in inhibiting arthritis and circumventing hepatotoxicity produced by MTX in arthritic animals.
J Ethnopharmacol. 2022 Jun;292():115200.
PMID: 35306043 [PubMed - indexed for MEDLINE]
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| 8. |
Frankincense vinegar-processing improves the absorption of boswellic acids by regulating bile acid metabolism.
Peng S, Song Z, Wang C, Liang D, Wan X, Liu Z, Lu A, Ning Z
BACKGROUND: Boswellic acids in Olibanum (known as frankincense) are potent anti-inflammatory properties in treating ulcerative colitis (UC), but its low bioavailability limited drug development. Evidence accumulated that vinegar processing of frankincense exerts positive effects on improving absorption of compositions. The underlying mechanism is unknown. In recent decades, spectacular growth and multidisciplinary integration of metabolic application were witnessed. The relationship between drug absorption and curative effect has been more or less established. However, it remains a knowledge gap in the field between drug absorption and endocrine metabolism.
PURPOSE: To investigate the enhancement mechanism of vinegar processing in the absorption of boswellic acids via the aspect of bile acid metabolism.
METHODS: The effects of raw frankincense (RF) and processed frankincense (PF) were compared by the UC model of rats. The plasma concentration of boswellic acids and the hepatic and colonic bile acids contents were quantified by UPLC-TQ-MS. The levels of mRNA and protein associated with bile acid metabolism were also compared.
RESULTS: The results showed that PF exhibited re-markable mitigating effects on UC with the elevated plasma level of boswellic acid and upregulated expression of the absorption-related protein multidrug resistance-associated protein 2 (MRP2) and organic anion transporting polypeptide 1B3 (OATP1B3) in the liver and colon. It improved colonic lithocholic acid (LCA), which promoted the expression of bile acid nuclear receptors constitutive androstane receptor (CAR) and pregnane X receptor (PXR), resulting in the upregulation of MRP2 and OATP1B3.
CONCLUSION: This paper revealed the mechanisms behind the absorption promotion effects of processing. Bile acids metabolism exhibits potential status in pharmaceutical development. The results shed light on the interdisciplinary collaboration between the metabolism and drug absorption fields.
Phytomedicine. 2022 Apr;98():153931.
PMID: 35104761 [PubMed - as supplied by publisher]
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| 9. |
Pharmacokinetics of solid lipid particles in healthy subjects.
Kulkarni PD, Damle ND, Hingorani L, Bhaskar VH, Ghante MR, Patil A, Gurjar M, Gota V
OBJECTIVES: The anti-inflammatory activity of extracts (BSE) is well known. BSE comprises boswellic acids (BA) such as 3--acetyl-11-keto--boswellic acid (AKBA) and 11--boswellic acid (KBA) as major constituents. One of the limitations of BAs is their poor oral bioavailability. The aim of the study was to prepare solid lipid particles of extract (SLBSP) to enhance the bioavailability of BAs.
METHODS: The pharmacokinetic profile of BAs was studied in 10 healthy human volunteers following a single oral dose of 333 mg of SLBSP. Pharmacokinetic blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 h post drug administration. Plasma KBA and AKBA levels were measured using a validated LC-MS/MS method. Pharmacokinetics parameters were estimated using Pheonix WinNonlin (Build 6.4.0.768) software.
RESULTS: Ten healthy human volunteers were included and peak plasma concentration was achieved in 1.5 and 2.3 h for AKBA and KBA respectively. Maximum plasma concentration () was 8.04 ± 1.67 ng/mL for AKBA and 23.83 ± 4.41 ng/mL for KBA whereas the corresponding area under the concentration-time curve (AUC) was 136.7 ± 56.77 ng/mL*h and 165.7 ± 24.5 ng/mL*h respectively. The elimination half-life () of AKBA and KBA was 6.8 ± 3.0 h and 2.45 ± 0.3 h respectively.
CONCLUSIONS: The SLBSP formulation of BSE showed enhanced oral bioavailability of BAs compared with historically reported data of unformulated BSE.
Drug Metab Pers Ther. 2021 Apr;36(3):215-221.
PMID: 34412175 [PubMed - indexed for MEDLINE]
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| 10. |
Pharmacokinetics of solid lipid particles in healthy subjects.
Kulkarni PD, Damle ND, Hingorani L, Bhaskar VH, Ghante MR, Patil A, Gurjar M, Gota V
OBJECTIVES: The anti-inflammatory activity of extracts (BSE) is well known. BSE comprises boswellic acids (BA) such as 3--acetyl-11-keto--boswellic acid (AKBA) and 11--boswellic acid (KBA) as major constituents. One of the limitations of BAs is their poor oral bioavailability. The aim of the study was to prepare solid lipid particles of extract (SLBSP) to enhance the bioavailability of BAs.
METHODS: The pharmacokinetic profile of BAs was studied in 10 healthy human volunteers following a single oral dose of 333 mg of SLBSP. Pharmacokinetic blood samples were collected at 0.5, 1, 1.5, 2, 2.5, 3, 4, 5, 6, 8, and 12 h post drug administration. Plasma KBA and AKBA levels were measured using a validated LC-MS/MS method. Pharmacokinetics parameters were estimated using Pheonix WinNonlin (Build 6.4.0.768) software.
RESULTS: Ten healthy human volunteers were included and peak plasma concentration was achieved in 1.5 and 2.3 h for AKBA and KBA respectively. Maximum plasma concentration ( ) was 8.04 ± 1.67 ng/mL for AKBA and 23.83 ± 4.41 ng/mL for KBA whereas the corresponding area under the concentration-time curve (AUC) was 136.7 ± 56.77 ng/mL*h and 165.7 ± 24.5 ng/mL*h respectively. The elimination half-life ( ) of AKBA and KBA was 6.8 ± 3.0 h and 2.45 ± 0.3 h respectively.
CONCLUSIONS: The SLBSP formulation of BSE showed enhanced oral bioavailability of BAs compared with historically reported data of unformulated BSE.
Drug Metab Pers Ther. 2021 Apr;():.
PMID: 33818023 [PubMed - as supplied by publisher]
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| 11. |
Development and validation of a sensitive UHPLC-MS/MS method for the measurement of β-elemonic acid in rat plasma and tissues and its application to pharmacokinetics and tissue distribution study.
Zhang Y, Huo XX, Cheng LY, Chen MY, Song L, Yu YL, Zhou K
β-Elemonic acid is one of the main active ingredients isolated from Boswellia carterii Birdw. which has been reported to exhibit potential anti-inflammatory and anti-cancer activities. There is few information about pharmacokinetics and tissue distribution of β-elemonic acid by now. In this study, an ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC-MS/MS) method has been developed and validated to determine β-elemonic acid in rat plasma and various tissues after intragastric administration. Oleanolic acid was chosen as an internal standard (IS) and the plasma/tissue samples were pretreated with one-step liquid-liquid extraction. Chromatographic separation was accomplished on Eclipse Plus C18 analytical column (2.1 × 50 mm, 1.8 μm) utilizing a gradient mobile phase system consisting of water (with 0.1% ammonia-solution) and acetonitrile. β-Elemonic acid and IS were detected and quantified using negative electrospray ionization in multiple reaction monitoring (MRM) mode with transitions of m/z 453.3 → 423.5 for β-elemonic acid and m/z 455.3 → 407.6 for IS. β-Elemonic acid showed good linearity over the investigated concentration range (r > 0.9934) in rat plasma and tissue sample. The method was successfully applied for determination of β-elemonic acid in bio-samples. A bimodal phenomenon appeared in the plasma concentration-time curve of the β-elemonic acid. The highest tissue concentrations were found in the intestine including jejunum, ileum and colon.
J Chromatogr B Analyt Technol Biomed Life Sci. 2021 Mar;1167():122566.
PMID: 33578281 [PubMed - indexed for MEDLINE]
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| 12. |
Simultaneous determination of five bioactive components of XiaoJin Capsule in normal and mammary gland hyperplasia rat plasma using LC-MS/MS and its application to a pharmacokinetic study.
Wang X, Lei H, Qi X, Guo X, Xu X, Zu X, Ye J
XiaoJin Capsule (XJC) is a classic Traditional Chinese Medicine formula for clinical treatment of thyroid nodules, mammary gland hyperplasia and breast cancer. For the specification and rational application of XJC in the future, an accurate and specific LC-MS/MS method was developed and validated for quantitative determination of five components in rat plasma after oral administration of XJC. The collected plasma samples were extracted by protein precipitation with methanol-acetonitrile (1:3, v/v) mixture solvent and separated on a C column using a gradient elution system. Mass spectrometry was performed on a triple quadrupole mass spectrometer, and samples were detected in positive ionization and multiple reactions monitoring mode. The method was properly validated in terms of linearity, precision, accuracy, recovery, matrix effect and stability. All calibration curves showed good linearity (r > 0.9910) over their concentration ranges. The intra- and inter-day precisions (RSD) were within 11.0%, and the LLOQ was 0.1, 0.2, 0.5, 7.5 and 7.5 ng/ml for aconine, songorine, neoline, 3-acetyl-11-keto-β-boswellic acid and 11-keto-β-boswellic acid, respectively. Extraction recovery, matrix effect and stability were satisfactory in rat plasma. This established method was successfully applied to a pharmacokinetics study of five compounds after oral administration of XJC to normal and mammary gland hyperplasia model rats.
Biomed Chromatogr. 2021 Mar;35(3):e5000.
PMID: 33460195 [PubMed - indexed for MEDLINE]
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| 13. |
Development of an eco-friendly biodegradable plastic from jack fruit peel cellulose with different plasticizers and Boswellia serrata as filler.
Reshmy R, Philip E, Vaisakh PH, Raj S, Paul SA, Madhavan A, Sindhu R, Binod P, Sirohi R, Pugazhendhi A, Pandey A
Pure nanocellulose was extracted from agricultural waste material namely jackfruit (Artocarpus heterophyllus) peel through acid hydrolysis. The extraction method utilizes soapnut solution as an eco-friendly bleaching agent in order to avoid environment polluting chlorinated chemicals. Various thin films were prepared by solvent casting nanocellulose and different plasticizers namely glycerol, polyethylene glycol, polyvinyl alcohol, triethyl citrate along with novel filler, Boswellia serrata commonly known as frankincense. Thin films were characterized by FT-IR, XRD and the surface modifications were investigated using FESEM. The physical, mechanical, thermal properties and biodegradability of the film were also reported. The surface morphology was improved by different plasticizers and a self-assembly was obtained due to more stable hydrogen bonding between the nanocellulose, plasticizers and filler during the film formation. Thermal investigations of plasticizers/Boswellia serrata incorporated thin films revealed an increase in glass transition temperature of nanocellulose. Results indicate that these films are biodegradable and compostable in nature and could be used as substitute for petroleum derived plastics.
Sci Total Environ. 2021 May;767():144285.
PMID: 33429269 [PubMed - indexed for MEDLINE]
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| 14. |
Enhanced Bioavailability of Boswellic Acid by : A Computational and Pharmacokinetic Study.
Vijayarani KR, Govindarajulu M, Ramesh S, Alturki M, Majrashi M, Fujihashi A, Almaghrabi M, Kirubakaran N, Ren J, Babu RJ, Smith F, Moore T, Dhanasekaran M
Chronic inflammation is a key culprit factor in the onset and progression of several diseases. Novel and pharmacologically effective therapeutic approaches are needed for new treatment remedy or improved pharmacokinetics and pharmacodynamics for existing synthetic drugs, in particular natural products. Boswellic acids are well-known natural products, with capacity to effectively retard inflammation without severe adverse effects. However, the therapeutic use of Boswellic acids are greatly hindered by its poor pharmacokinetic properties. Co-administration strategies that facilitate the oral absorption and distribution of Boswellic acids should lead to a safe and more effective use of this product prophylactically and therapeutically in inflammatory disorders. In this study, we examined the effect of extract on the absorption and bioavailability of Boswellic acid in rabbits. In addition, we further explored computational pharmacodynamic interactions between and Boswellic acid. extract at 2.5 and 10 mg/kg, increased the bioavailability of Boswellic acid ( < 0.05). Based on our drug-based computational modeling, cytochrome P450 (CYP450)-mediated mechanism was involved in increased bioavailability. These findings confirmed that with Boswellic acid may be administered orally together for effective therapeutic efficacy. Thus, our studies support the application of with Boswellic acid as a novel therapeutic avenue in diseases associated with inflammation.
Front Pharmacol. 2020;11():551911.
PMID: 33384596 [PubMed - as supplied by publisher]
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| 15. |
Phyto-Facilitated Bimetallic ZnFeO Nanoparticles via Boswellia carteri: Synthesis, Characterization, and Anti-Cancer Activity.
Imraish A, Al-Hunaiti A, Abu-Thiab T, Ibrahim AA, Hwaitat E, Omar A
BACKGROUND: The growing dissatisfaction with the available traditional chemotherapeutic agents has enhanced the need to develop new methods for obtaining materials with more effective and safe anti-cancer properties. Over the past few years, the usage of metallic nanoparticles has been a target for researchers of different scientific and commercial fields due to their tiny sizes, environment-friendly properties, and a wide range of applications. To overcome the obstacles of traditional physical and chemical methods for the synthesis of such nanoparticles, a new, less expensive, and eco-friendly method has been adopted using natural existing organisms as a reducing agent to mediate the synthesis of the desired metallic nanoparticles from their precursors, a process called green biosynthesis of nanoparticles.
OBJECTIVE: In the present study, zinc-iron bimetallic nanoparticles (ZnFeO) were synthesized via an aqueous extract of Boswellia carteri resin mixed with zinc acetate and iron chloride precursors, and they were tested for their anticancer activity.
METHODS: Various analytic methods were applied for the characterization of the phyto synthesized ZnFeO, and they were tested for their anticancer activity against MDA-MB-231, K562, MCF-7 cancer cell lines, and normal fibroblasts.
RESULTS: Our results demonstrate the synthesis of cubic structured bimetallic nanoparticles ZnFeO with an average diameter of 10.54 nm. MTT cytotoxicity assay demonstrates that our phyto-synthesized ZnFeO nanoparticles exhibited a selective and potent anticancer activity against K562 and MDA-MB-231 cell lines with IC50 values 4.53 μM and 4.19 μM, respectively.
CONCLUSION: In conclusion, our biosynthesized ZnFeO nanoparticles show a promising, environmentally friendly, and low coast chemotherapeutic approach against selective cancers with a predicted low adverse side effect toward normal cells. Further, in vivo, advanced animal research should be done to execute their applicability in living organisms.
Anticancer Agents Med Chem. 2021;21(13):1767-1772.
PMID: 33342418 [PubMed - indexed for MEDLINE]
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| 16. |
Modified Bacterial Cellulose Dressings to Treat Inflammatory Wounds.
Beekmann U, Zahel P, Karl B, Schmölz L, Börner F, Gerstmeier J, Werz O, Lorkowski S, Wiegand C, Fischer D, Kralisch D
Natural products suited for prophylaxis and therapy of inflammatory diseases have gained increasing importance. These compounds could be beneficially integrated into bacterial cellulose (BC), which is a natural hydropolymer applicable as a wound dressing and drug delivery system alike. This study presents experimental outcomes for a natural anti-inflammatory product concept of boswellic acids from frankincense formulated in BC. Using esterification respectively (resp.) oxidation and subsequent coupling with phenylalanine and tryptophan, -modification of BC was tested to facilitate lipophilic active pharmaceutical ingredient (API) incorporation. Diclofenac sodium and indomethacin were used as anti-inflammatory model drugs before the findings were transferred to boswellic acids. By acetylation of BC fibers, the loading efficiency for the more lipophilic API indomethacin and the release was increased by up to 65.6% and 25%, respectively, while no significant differences in loading could be found for the API diclofenac sodium. -modifications could be made while preserving biocompatibility, essential wound dressing properties and anti-inflammatory efficacy. Eventually, in vitro wound closure experiments and evaluations of the effect of secondary dressings completed the study.
Nanomaterials (Basel). 2020 Dec;10(12):.
PMID: 33327519 [PubMed - as supplied by publisher]
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| 17. |
Antiproliferative effects of boswellic acid-loaded chitosan nanoparticles on human lung cancer cell line A549.
Solanki N, Mehta M, Chellappan DK, Gupta G, Hansbro NG, Tambuwala MM, Aa Aljabali A, Paudel KR, Liu G, Satija S, Hansbro PM, Dua K, Dureja H
In the present study boswellic acids-loaded chitosan nanoparticles were synthesized using ionic gelation technique. The influence of independent variables were studied and optimized on dependent variables using central composite design. The designed nanoparticles were observed spherical in shape with an average size of 67.5-187.2 nm and have also shown an excellent entrapment efficiency (80.06 ± 0.48). The cytotoxicity assay revealed enhanced cytotoxicity for drug-loaded nanoparticles in contrast to the free drug having an IC value of 17.29 and 29.59 μM, respectively. Flow cytometry confirmed that treatment of cells with 40 μg/ml had arrested 22.75 ± 0.3% at SubG phase of the cell cycle when compared with untreated A459 cells. The observed results justified the boswellic acids-loaded chitosan nanoparticles were effective due to greater cellular uptake, sustained intercellular drug retention and enhanced antiproliferative effect by inducing apoptosis.
Future Med Chem. 2020 Nov;12(22):2019-2034.
PMID: 33124483 [PubMed - indexed for MEDLINE]
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| 18. |
-Mediated Silver Nanoparticles Inhibited Acute Myeloid Leukemia (AML) Kasumi-1 Cells by Inducing Cell Cycle Arrest.
Adebayo IA, Usman AI, Shittu FB, Ismail NZ, Arsad H, Muftaudeen TK, Samian MR
BACKGROUND: Acute myeloid leukemia (AML) persists to be a major health problem especially among children as effective chemotherapy to combat the disease is yet to be available. is a well-known herb that is traditionally used for treatment and management of many diseases including degenerative diseases. In this study, silver nanoparticles were synthesized from the phytochemicals of stem bark aqueous extract. The silver nanoparticles were characterized by carrying out Fourier Transform Infrared (FTIR) spectroscopy, Energy Filtered Scanning Electron Microscopy (FESEM), X-ray diffraction, and Dynamic Light Scattering (DLS) analyses. Antioxidant capacity of the nanoparticles was evaluated using 2,2-diphenyl-1-picrylhydrazyl (DPPH) assay, and the antiproliferative effect of the nanoparticles on Kasumi-1 leukemia cells was investigated using PrestoBlue assay. Flow cytometry analysis was performed to observe the effect of the nanoparticles on the leukemia cell cycle progression.
RESULTS: Our findings revealed that the synthesized silver nanoparticles were formed from electrons of the plant phytochemicals which include aromatic compounds, ethers, and alkynes. FESEM analysis revealed that the sizes of the nanoparticles range from 12 nm to 101 nm; however, DLS analysis estimated a larger average size of the nanoparticles (108.3 nm) because it measured the hydrodynamic radii of the nanoparticles. The zeta potential of the nanoparticles was -16 nm, and the XRD pattern of the nanoparticles has distinct peaks at 38.02°, 42.94°, 64.45°, 77.20°, and 81.47°, which is typical of face-centered cubic (fcc) structure of silver. The Trolox Equivalence Antioxidant Capacity (TEAC) of the nanoparticles was estimated to be 300.91 M Trolox/mg silver nanoparticles. The nanoparticles inhibited Kasumi-1 cell proliferation. The half minimal inhibitory concentrations (IC50s) that inhibited Kasumi-1 cell proliferation are 49.5 g/ml and 13.25 g/ml at 48 and 72 hours, respectively. The nanoparticles induced cell cycle arrest in the Kasumi-1 cells at S (5% increase) and G2/M (3% increase) phases.
CONCLUSION: The nanoparticles synthesized from the stem bark extract of inhibit the growth of Kasumi-1 leukemia cells by activating cell cycle arrest; thus, they are potential antileukemic agents.
Bioinorg Chem Appl. 2020;2020():8898360.
PMID: 33029114 [PubMed - as supplied by publisher]
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| 19. |
Formulation of Nanospanlastics as a Promising Approach for Improving the Topical Delivery of a Natural Leukotriene Inhibitor (3-Acetyl-11-Keto-β-Boswellic Acid): Statistical Optimization, in vitro Characterization, and ex vivo Permeation Study.
Badria F, Mazyed E
PURPOSE: The current study aimed to discuss the potential of nanospanlastics as a surfactant-based vesicular system for improving the topical delivery of 3-acetyl-11-keto-β-boswellic acid (AKBA). AKBA is a potent anti-inflammatory drug, but it has poor oral bioavailability due to its poor aqueous solubility. Moreover, the topical delivery of AKBA is difficult due to its high lipophilicity. To overcome these drawbacks, AKBA was formulated as deformable elastic nanovesicles and nanospanlastics, for improving its topical delivery.
MATERIALS AND METHODS: AKBA-loaded spanlastic nanovesicles (SNVs) were formulated by ethanol injection technique according to 2 factorial design using Span 60 as a non-ionic surfactant and Tween 80 as edge activator (EA) to investigate the effect of different independent variables on entrapment efficiency (EE%), % drug released after 8 hr (Q) and particle size (PS) using Design-Expert software. In vitro characterization, stability test and ex vivo permeation study of the optimized formula were performed.
RESULTS: The choice of the optimized formula was based on the desirability criteria. F7 was selected as the optimized formula because it has the highest desirability value of 0.648. F7 exhibited EE% of 90.04±0.58%, Q of 96.87±2.67%, PS of 255.8±2.67 nm, and zeta potential of -49.56 mV. F7 appeared as spherical well-defined vesicles in both scanning electron microscope (SEM) and transmission electron microscope (TEM). The Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC) studies investigated the absence of interaction between AKBA and different excipients and good encapsulation of AKBA within SNVs. F7 retained both physical and chemical stability after storage for 3 months at 4-8 °C. Ex vivo permeation test exhibited significant enhancement of permeability of F7 across rat skin than the free drug.
CONCLUSION: Nanospanlastics could be a promising approach for improving the permeability and topical delivery of AKBA.
Drug Des Devel Ther. 2020;14():3697-3721.
PMID: 32982176 [PubMed - indexed for MEDLINE]
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| 20. |
A Validated LC-MS/MS Method for Simultaneous Determination of 3-O-Acetyl-11-Keto-β-Boswellic Acid (AKBA) and its Active Metabolite Acetyl-11-Hydroxy-β-Boswellic Acid (Ac-11-OH-BA) in Rat Plasma: Application to a Pharmacokinetic Study.
Sharma T, Jana S
The aim of this study was to develop and validate a new, rapid, sensitive, selective and reliable liquid chromatography-tandem mass spectrometry method for simultaneous determination of 3-O-Acetyl-11-keto-β-boswellic acid (AKBA) and its active metabolite 3-O-Acetyl-11-hydroxy-β-boswellic acid (Ac-11-hydroxy-BA) in rat plasma. Both analytes (AKBA and Ac-11-hydroxy-BA) and the internal standard (IS, ursolic acid) were extracted from 100 μL of rat plasma by protein precipitation. Chromatographic separation was achieved on PRP-H1 RP-C18 column (75 mm × 2 mm, 1.6 μm) using acetonitrile-water (95.5 v/v) as the mobile phase. Mass detection was conducted by electrospray ionization in positive ion multiple reaction monitoring (MRM) mode. A linear dynamic range of 1-1,000 ng/mL for both AKBA and Ac-11-hydroxy-BA was established with mean correlation coefficient (r (1)) of 0.999. Intra- and inter-day precision (% CV) of analysis were found in the range of 1.9-7.4%. The accuracy determined for these analytes ranged from 92.4 to 107.2%. The extraction recoveries for both analytes ranged from 92.6 to 97.3% for spiked plasma samples and were consistent. The % change in stability samples compared to nominal concentration ranged from 0.4 to 4.2%. This method was successfully tested to a pharmacokinetic (PK) study for estimation of AKBA and acetyl-11-hydroxy-BA in rat plasma following oral administration of AKBA. This method has been validated with the advantage of shorter run time that can be used for high-throughput analysis and has been successfully applied to the pharmacokinetic study of AKBA in rats.
J Chromatogr Sci. 2020 Jun;58(6):485-493.
PMID: 32134105 [PubMed - indexed for MEDLINE]
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| 21. |
Evaluation of mucoadhesive property and the effect of gum on intranasal vaccination against small ruminant morbillivirus infection (PPR).
Mumin FI, Emikpe BO, Odeniyi MA
A study was conducted to evaluate mucoadhesive property and immunomodulatory effect of phytogenic gums from and on intranasal Peste des petits ruminants (PPR) vaccination in goats and sheep in an ex-vivo and in-vivo situations. Plant gums were purified, dried and compressed into 500gm tablets. Modified shear stress measurement technique was used on freshly excised trachea and intestine tissues of goat to measure peak adhesion time. Forty eight animals (24 goats and 24 sheep) were divided into eight groups (of 3 goats and 3 sheep) and immunized intranasally with gum-vaccine combinations in two ratios (1:1, 1:2). Antibody against PPR virus was measured on day 14, 28, 42 and 56 post vaccination using H-based PPR bELISA. The peak adhesion time of the different gums was transient. PPR virus antibodies were detected in all immunized goats and sheep but not in unvaccinated control. The best percentage inhibition was recorded for Boswellia carteri-vaccine combination group at a ratio of 1:1. Administration of -PPR vaccine combination through intranasal or subcutaneous route, elicited similar antibody titre, implying that the intranasal route may be used as a non-invasive alternative delivery in PPR vaccination of small ruminants.
J Immunoassay Immunochem. 2020 May;41(3):311-321.
PMID: 32119592 [PubMed - indexed for MEDLINE]
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| 22. |
Investigation of Molecular Properties that Influence the Permeability and Oral Bioavailability of Major β-Boswellic Acids.
Sharma T, Jana S
BACKGROUND AND OBJECTIVES: Boswellic acids (BAs) include β-boswellic acid (BA), 3-acetyl-β-boswellic acid, 11-keto-β-boswellic acid, 3-acetyl-11-keto-β-boswellic acid, β-boswellic alcohol, and 3-acetyl-11-hydroxy-β-BA from Boswellia species, and are the main active ingredients of Boswellia serrata extracts (BSE). BSE have been used for the treatment of different inflammatory diseases; however, their pharmaceutical development has been severely limited by their poor oral bioavailability. The aims of this study were to investigate the molecular properties of six BAs, and to determine their experimental aqueous solubility, partition coefficient (Log P), gastrointestinal stability, adsorption-desorption kinetics, and permeability studies.
METHODS: The physicochemical properties of six BAs were obtained from SMILES representations using ChemDraw, and MarvinSketch. The molecular properties were also determined experimentally. The permeability studies were performed using parallel artificial membrane permeability assay (PAMPA), and Caco-2 cells.
RESULTS: The experimental Log P values of BAs correlated well (R = 0.94) with the calculated Log P values. Metabolic stability data confirmed that BAs were found to be unstable in simulated gastrointestinal fluids and intestinal S9 fractions. The apparent permeability (P) range of BAs in both PAMPA and Caco-2 for the apical (AP) to basolateral (BL) was in the range of 0.52 ± 0.05 × 10 to 2.84 ± 0.14 × 10cm/s. The efflux ratio of P (BL → AP) to P (AP → BL) for all BAs was < 2 in Caco-2 cells, suggesting greater permeability in the absorptive direction. Caco-2 cell adsorption studies confirmed the accumulation of BAs (35-55%) inside the enterocytes. These compounds exhibited a strong correlation between PAMPA and Caco-2 cell monolayer permeation data.
CONCLUSIONS: The results of the present study have shown an empirical relationship between the molecular properties and intestinal absorption of BAs for the first time.
Eur J Drug Metab Pharmacokinet. 2020 Apr;45(2):243-255.
PMID: 31786725 [PubMed - indexed for MEDLINE]
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| 23. |
A dual functional probe for assessing human CYP450 3A5 and 3A enzymes bioactivities.
Yan F, Cui Y, An Y, Ning J, Zhao X, Feng L, Huo X, Wang C, Lv C, Ma X, Tian X
CYP3A5 plays a vital role in the drug metabolism, it displays varied expression levels among individuals and is easily influenced by genetic polymorphisms and some diseases. A dual function probe isobutyryl-11-keto--boswellic acid (IKBA) was developed; it possessed a high selectivity toward CYP3A5 and CYP3A enzymes for its two individual metabolites, respectively. The probe has the high accuracy and wide applicability in measuring the real activity of CYP3A5. Finally, IKBA was successfully used for the evaluation of the activity of CYP3A5 and CYP3A enzymes in various bio samples. IKBA could serve as a useful tool for exploring the physiology and pathology functions of CYP3A5 and give some useful guidance for the rational use of clinical drugs.
Future Med Chem. 2019 Nov;11(22):2891-2903.
PMID: 31702381 [PubMed - indexed for MEDLINE]
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| 24. |
Loading AKBA on surface of silver nanoparticles to improve their sedative-hypnotic and anti-inflammatory efficacies.
Khan A, Al-Harrasi A, Rehman NU, Sarwar R, Ahmad T, Ghaffar R, Khan H, Al-Amri I, Csuk R, Al-Rawahi A
Acetyl-11-keto--boswellic acid (AKBA) is a potent anti-inflammatory compound limited by its low water solubility and bioavailability. To load AKBA on silver nanoparticles (AgNPs) to improve bioavailability and water solubility of the compound. AKBA-AgNPs were chemically synthesized and characterized by UV-Vis spectrophotometry, Fourier transform infrared spectroscopy, scanning electron microscopy and transmission electron microscopy. AKBA and AKBA-Ag were studied for their sedative-hypnotic and anti-inflammatory efficacies. Pretreatment with AKBA or AKBA-Ag caused significant dose-dependent sedative-hypnotic effects at 5 and 10 mg/kg intraperitoneal. The effects of AKBA-loaded AgNPs caused pronounced changes in mice compared with those of AKBA, and the AKBA-AgNPs demonstrated anti-inflammatory effects that were superior to those of AKBA. The loading of AKBA on nanoparticles improved its pharmacokinetic effects, and capacity for drug delivery.
Nanomedicine (Lond). 2019 Nov;14(21):2783-2798.
PMID: 31617445 [PubMed - indexed for MEDLINE]
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| 25. |
Pharmacokinetic assessment of constituents of Boswellia serrata, pine bark extracts, curcumin in combination including methylsulfonylmethane in healthy volunteers.
Liu X, Hunter DJ, Eyles J, McLachlan AJ, Adiwidjaja J, Eagles SK, Wang X
OBJECTIVES: Dietary supplements are increasingly used by people with osteoarthritis. Boswellia serrata extract, curcumin, pine bark extract and methylsulfonylmethane have been identified as having the largest effects for symptomatic relief in a systematic review. It is important to understand whether any pharmacokinetic interactions are among the major constituents of these supplements so as to provide information when considering the combination use of these supplements. The aim of this study was to investigate the pharmacokinetics of the constituents alone and in combination.
METHODS: This study was a randomized, open-label, single-dose, four-treatment, four-period, crossover study with 1-week washout. The pharmacokinetics of the constituents of these supplements when dosed in combination with methylsulfonylmethane were compared to being administered alone. Plasma samples were obtained over 24 h from 16 healthy participants. Eight major constituents were analysed using a validated ultra-high-performance liquid chromatography-tandem mass spectrometry assay.
KEY FINDINGS: The pharmacokinetics of each constituent was characterized, and there were no significant differences in the pharmacokinetic profiles of the constituents when administered as a combination, relative to the constituents when administered alone (P > 0.05).
CONCLUSIONS: These data suggest that interactions between the major constituents of this supplement combination are unlikely and therefore could be investigated to manage patients with osteoarthritis without significant concerns for possible pharmacokinetic interactions.
J Pharm Pharmacol. 2020 Jan;72(1):121-131.
PMID: 31608447 [PubMed - indexed for MEDLINE]
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| 26. |
The Effects of Vinegar Processing on the Changes in the Physical Properties of Frankincense Related to the Absorption of the Main Boswellic Acids.
Liang D, Ning Z, Song Z, Wang C, Liu Y, Wan X, Peng S, Liu Z, Lu A
Boswellic acids (BAs), as the main components of frankincense, exhibit notable anti-inflammatory properties. However, their pharmaceutical development has been severely limited by their poor oral bioavailability. Traditional Chinese medicinal processing, called Pao Zhi, is believed to improve bioavailability, yet the mechanism is still completely unclear. Previous research suggested that the bioavailability of a drug can be influenced by physical properties. This paper was designed to investigate the physical properties of frankincense and processed frankincense, including the surface morphology, particle size, polydispersity index (PDI), zeta potential (ZP), specific surface area, porosity, and viscosity. The differences in the intestinal absorption characteristics and equilibrium solubilities between frankincense and processed frankincense were determined by an ultra-high-performance liquid chromatography coupled with a triple quadrupole electrospray tandem mass spectrometry (UHPLC-TQ-MS) analysis method. The results showed that vinegar processing can alter the surface morphology, decrease the particle size and PDI, raise the absolute values of the ZP, specific surface area and porosity, and drop the viscosity of frankincense. Meanwhile, the rates of absorption and dissolution of the main BAs were increased after the processing of frankincense. The present study proves that the physical properties were changed after processing, in which case the bioavailability of frankincense was enhanced.
Molecules. 2019 Sep;24(19):.
PMID: 31547594 [PubMed - indexed for MEDLINE]
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| 27. |
Ex-vivo intestinal absorption study of boswellic acid, cyclodextrin complexes and poloxamer solid dispersions using everted gut sac technique.
Tambe A, Mokashi P, Pandita N
Acetyl- Keto-β-boswellic acid (AKBA) is a pentacyclic triterpenic acid found in gum resin of Boswellia serrata. Even though it is shown to have anti-inflammatory activity, its bioavailability gets limited due to its poor aqueous solubility and permeability. The present study, hence, deals in enhancement of the intestinal absorption of AKBA from total boswellic acid fraction (TA fraction) using cyclodextrin (CD) and poloxamer solid dispersion (PXM SDs) formulations. Absorption studies were performed using the everted gut sac model prepared from rat jejunum. The glucose uptake assay was performed to show viability of gut sac tissue. The apparent permeability (P) value of AKBA from TA fraction was 1.08 ± 0.17 × 10 which was found to be increased by 10-14 fold with CD complex and SD formulations. The intestinal absorption studies showed highest absorption of AKBA from HP-β-CD complex and PXM 407 SD as compared to that from TA fraction. From this study, it can be concluded that HP-β-CD and PXM 407 effectively enhanced intestinal absorption through improved solubility, highlighting their role as efficient drug delivery agents and bioavailability enhancers.
J Pharm Biomed Anal. 2019 Apr;167():66-73.
PMID: 30743157 [PubMed - indexed for MEDLINE]
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| 28. |
Oral administration of a lecithin-based delivery form of boswellic acids (Casperome®) for the prevention of symptoms of irritable bowel syndrome: a randomized clinical study.
Riva A, Giacomelli L, Togni S, Franceschi F, Eggenhoffner R, Zuccarini MC, Belcaro G
BACKGROUND: The purpose of this study was to evaluate the long-term efficacy and the safety of a lecithin-based delivery form of boswellic acids from Boswellia serrata (Casperome®) for the prevention of symptoms in otherwise healthy subjects with mild irritable bowel syndrome (IBS).
METHODS: The study included 69 otherwise healthy participants with a mild form of IBS who completed a 6-month follow-up period. In total, 34 subjects were assigned to the standard management (SM) group: diet and, if needed, hyoscine butylbromide (Buscopan®) or papaverine hydrochloride + 10 mg of Atropa belladonna extract; 35 subjects were assigned to supplementation with the Boswellia serrata lecithin-based delivery form (one tablet/day; Casperome®). IBS signs and symptoms were evaluated at inclusion (T0), after 3 (T1) and 6 months (T2). The numbers of patients who needed rescue medication were recorded. Adverse events were also evaluated.
RESULTS: At baseline, the groups were comparable in terms of demographic and clinical characteristics. At follow-up, compared with the SM group, the Boswellia group showed lower mean score values for almost all self-assed IBS symptoms. A significantly lower need for rescue medications and consultations or medical evaluation/admissions was found in the Boswellia group compared with the SM group. The incidence of minimal adverse events - mainly stipsis - was significantly higher in the SM group. Oxidative stress at T2 was significantly decreased in Boswellia-supplemented subjects.
CONCLUSIONS: Boswellia serrata lecithin-based delivery form (Casperome®) appears to be effective and safe in improving signs and symptoms in IBS subjects who are otherwise healthy, particularly in comparison with symptomatic drug treatment that may cause side effects and stiptis.
Minerva Gastroenterol Dietol. 2019 Mar;65(1):30-35.
PMID: 30676012 [PubMed - indexed for MEDLINE]
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| 29. |
Boswellia serrata oleo-gum-resin and β-boswellic acid inhibits HSV-1 infection in vitro through modulation of NF-кB and p38 MAP kinase signaling.
Goswami D, Mahapatra AD, Banerjee S, Kar A, Ojha D, Mukherjee PK, Chattopadhyay D
BACKGROUND: Herpes Simplex Virus (HSV), a highly contagious pathogen, is responsible for causing lifelong oral to genital infection in human. Boswellia serrata oleo-gum-resin possesses a strong traditional background of treating diverse skin ailments including infection but its effect on HSV-1 has not been examined yet.
PURPOSE: To exploit its potential, we aimed to explore the antiviral activity of methanol extract of B. serrata oleo-gum-resin (BSE) and one of its major constituent β-boswellic acid (BA) against HSV-1 along with the underlying mechanism of action involved.
METHODS: BSE was subjected to RP-HPLC analysis to quantify the active constituent. Cytotoxicity (CC) and antiviral activity were evaluated by MTT and plaque reduction assay, followed by the determination of median effective concentration (EC). The mode of antiviral activity was assessed by time-of-addition assay and confirmed by reverse transcriptase-PCR (RT-PCR). Further, the expressions of various cytokines were measured by RT-PCR, while the proteins by Western blot.
RESULTS: BSE and BA potently inhibited wild-type and a clinical isolate of HSV-1 (EC 5.2-6.2 and 12.1-14.63 μg/ml), with nearly-complete inhibition (EC) at 10 and 30 μg/ml, respectively. The inhibitory effect was significant at 1 h post-infection and effective up to 4 h. Based on target analysis we examined the inhibition of NF-κB, essential for virus replication, and observed significant down-regulation of NF-κB, and p38 MAP-kinase activation, with reduced expression of tumor necrosis factor (TNF)-α, Interleukin (IL)-1β and IL-6, involved in scheming NF-κB signaling.
CONCLUSION: Thus, our results support the ethnomedicinal use of BSE in skin infection by inhibiting HSV-1 through the modulation of NF-κB and p38 MAPK pathway.
Phytomedicine. 2018 Dec;51():94-103.
PMID: 30466633 [PubMed - indexed for MEDLINE]
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| 30. |
Adsorption kinetics, isotherm, and thermodynamics studies of acetyl-11-keto-β-boswellic acids (AKBA) from Boswellia serrata extract using macroporous resin.
Niphadkar SS, Rathod VK
An acetyl-11-keto-β-boswellic acid (AKBA) is potent anti-inflammatory agent found in Boswellia serrata oleogum resin. Adsorption characteristics of AKBA from B. serrata were studied using macroporous adsorbent resin to understand separation and adsorption mechanism of targeted molecules. Different macroporous resins were screened for adsorption and desorption of AKBA and Indion 830 was screened as it showed higher adsorption capacity. The kinetic equations were studied and results showed that the adsorption of AKBA on Indion 830 was well fitted to the pseudo first-order kinetic model. The influence of two parameters such as temperature (298, 303, and 308 K) and pH (5-8) on the adsorption process was also studied. The experimental data was further investigated using Langmuir, Freundlich, and Temkin isotherm models. It was observed that Langmuir isotherm model was found to be the best fit for AKBA adsorption by Indion 830 and highest adsorption capacity (50.34 mg/g) was obtained at temperature of 303 K. The values of thermodynamic parameters such as the change of Gibbs free energy (ΔG*), entropy (ΔS*), and enthalpy (ΔH*), indicated that the process of adsorption was spontaneous, favourable, and exothermic.
Prep Biochem Biotechnol. 2017 Sep;47(8):804-812.
PMID: 28662360 [PubMed - indexed for MEDLINE]
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| 31. |
New water soluble glycosides of 11-keto-β-boswellic acid: A paradigm.
Manjunath BN, Shenvi S, Raja A, Reddy GC
Though several glycosides of various triterpenes are known, but surprisingly no boswellic acid glycosides are reported so far. With a view to make water soluble boswellic acids, prepared glycosides of 11-keto boswellic acid for the first time. Naturally occurring boswellic acids which are anti-inflammatory agents are lipophylic in nature and thus, become a limiting factor in terms of their bioavailability. Among boswellic acids, 11-keto-β-boswellic acid is found to exhibit superior biological activity and hence successfully prepared its glucosyl and maltosyl derivatives viz., 11-keto-β-boswellic acid-24-O-β-D-glucopyranoside (9) and 11-keto-β-boswellic acid-24-O-α-D-glucopyranosyl-(1 → 4)-β-D-glucopyranoside (15) which are water soluble. Both these compounds are soluble in water to the extent of 10% (w/w) which is very significant.
Nat Prod Res. 2018 Jan;32(2):154-161.
PMID: 28627258 [PubMed - indexed for MEDLINE]
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| 32. |
P-gp modulatory acetyl-11-keto-β-boswellic acid based nanoemulsified carrier system for augmented oral chemotherapy of docetaxel.
Pandey G, Mittapelly N, Valicherla GR, Shukla RP, Sharma S, Banala VT, Urandur S, Jajoriya AK, Mitra K, Mishra DP, Gayen JR, Mishra PR
In spite of being a very potent and promising drug against many types of cancer, docetaxel suffers the disadvantage of low solubility and poor bioavailability rendering it unsuitable for oral administration. Also, the available marketed formulation for intravenous administration has its inherent drawbacks owing to the presence of polysorbate 80. Here, we exploited the anticancer and P-gp inhibitory potential of naturally occurring frankincense oil to fabricate a stable docetaxel loaded nanoemulsified carrier system for oral delivery. The nanoemulsion possessing desirable particle size (122±12nm), polydispersity (0.086±0.007) and zeta potential (-29.8±2.1mV) was stable against all type of physical stresses and simulated physiological conditions tested. The formulation showed higher uptake in Caco-2 cells and inhibited P-gp transporter significantly (P<0.05). In MDA-MB-231 cells, it showed less IC, arrested cells in G2-M phase and exhibited higher degree of apoptosis than marketed formulation Taxotere. The 182.58±4.16% increment in relative oral bioavailability led to higher in vivo anti-proliferative activity manifesting 19% more inhibition than Taxotere. Conclusively, it is revealed that the developed nanoemulsion will be a propitious approach towards alternative docetaxel therapy.
Colloids Surf B Biointerfaces. 2017 Jul;155():276-286.
PMID: 28437753 [PubMed - indexed for MEDLINE]
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| 33. |
A single-dose, randomized, cross-over, two-way, open-label study for comparing the absorption of boswellic acids and its lecithin formulation.
Riva A, Morazzoni P, Artaria C, Allegrini P, Meins J, Savio D, Appendino G, Schubert-Zsilavecz M, Abdel-Tawab M
BACKGROUND: The oral administration of the gum resin extracts of Indian frankincense (Boswellia serrata Roxb. ex Colebr) results in very low plasma concentrations of boswellic acids (BAs), being far below the pharmacologically active concentrations required in vitro for anti-inflammatory activity. For that reason the use of Indian frankincense in clinical practice and pharmaceutical development has substantially lagged behind. Recently the application of new formulation technologies resulted in a formulation of frankincense extract with lecithin, which revealed improved absorption and tissue penetration of BAs in a rodent study, leading for the first time to plasma concentrations of BAs in the range of their anti-inflammatory activity.
PURPOSE: In order to verify these encouraging results in humans, the absorption of a standardized Boswellia serrata extract (BE) and its lecithin formulation (CSP) was comparatively investigated in healthy volunteers.
STUDY DESIGN: According to a randomized cross-over design with two treatments, two sequences and two periods, 12 volunteers alternatively received the lecithin-formulated Boswellia extract (CSP) or the non-formulated Boswellia extract (BE) at a dosage of 2×250mg capsules.
METHODS: The plasma concentrations of the six major BAs (KBA, AKBA, βBA, αBA, AβBA, AαBA) were determined using LC/MS.
RESULTS: With the exception of KBA, a significantly higher (both in terms of weight-to-weight and molar comparison) and quicker absorption of BAs from the lecithin formulation was observed, leading to C in the range required for the interaction with their molecular targets.
CONCLUSION: These findings pave the way to further studies evaluating the clinical potential of BAs, and verify the beneficial effect of lecithin formulation to improve the absorption of poorly soluble phytochemicals.
Phytomedicine. 2016 Nov;23(12):1375-1382.
PMID: 27765357 [PubMed - indexed for MEDLINE]
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| 34. |
Metabolic Profile of 3-Acetyl-11-Keto-β-Boswellic Acid and 11-Keto-β-Boswellic Acid in Human Preparations In Vitro, Species Differences, and Bioactivity Variation.
Cui Y, Tian X, Ning J, Wang C, Yu Z, Wang Y, Huo X, Jin L, Deng S, Zhang B, Ma X
3-Acetyl-11-keto-β-boswellic acid (AKBA) and 11-keto-β-boswellic acid (KBA) are widely used in the clinic as anti-inflammatory drugs. However, these drugs have the poor bioavailability, which may be caused by their extensive metabolism. In this study, we systemically characterized both phase I and II metabolism of AKBA and KBA in vitro. In total, four major metabolites were firstly biosynthesized and identified using 1D and 2D NMR spectroscopy. Among them, three metabolites were novel. The kinetic parameters (K m , V max , CL int, and K i ) were also analyzed systematically in various biological samples. Finally, the deacetylation of AKBA and hydroxylation of KBA were confirmed to be the major metabolic pathways based on their large CL int and the high amounts of KBA (46.7%) and hydroxylated KBA (50.8%) along with a low amount of AKBA (2.50%) in human primary hepatocytes. Carboxylesterase 2 (CE2) selectively catalyzed the deacetylation of AKBA to form KBA. Although CYP3A4, CYP3A5, and CYP3A7 catalyzed the metabolism of KBA, CYP3A4 played a predominant role in the hydroxylation reaction of KBA in human. Notably, deacetylation and regioselective hydroxylation exhibited considerable species differences. Deacetylation was only observed in human liver microsomes and primary human hepatocytes; 21- and 20-mono-hydroxylation of KBA were primarily observed in human, monkey, and dog; and 16- and 30-mono-hydroxylation were observed in other species. More importantly, all four mono-hydroxylation metabolites exhibited a moderate anti-inflammatory activity. The 21- and 20-hydroxylation metabolites inhibited the expression of iNOS, the LPS-induced activation of IkBα and p65 phosphorylation, and suppressed p65 nuclear translocation in RAW264.7 cells.
AAPS J. 2016 Sep;18(5):1273-1288.
PMID: 27329304 [PubMed - indexed for MEDLINE]
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| 35. |
Nanoparticle formulation of 11-keto-β-boswellic acid (KBA): anti-inflammatory activity and in vivo pharmacokinetics.
Bairwa K, Jachak SM
CONTEXT: The oleo-gum-resin of Boswellia serrata Roxb. (Burseraceae) is widely used for the treatment of inflammatory diseases such as osteoarthritis, rheumatoid arthritis and cancer. Anti-inflammatory activity of 11-keto-β-boswellic acid (KBA) is impeded by poor oral bioavailability due to its high lipid solubility, rapid phase-1 metabolism and poor intestinal permeability.
OBJECTIVE: This study developed a poly-dl-lactide-co-glycolide-based nanoparticle formulation of KBA to improve its oral bioavailability and in vivo anti-inflammatory activity.
MATERIALS AND METHODS: KBA was isolated from the oleo-gum resin of B. serrata, and its nanoparticle formulation (KBA-NPs) was prepared by the emulsion-diffusion-evaporation method. Oral bioavailability of KBA and KBA-NPs was studied at 50 mg/kg p.o. dose in Sprague-Dawley rats, and further evaluated for in vivo anti-inflammatory activity in carrageenan-induced rat paw oedema assay at the same dose level.
RESULTS: The prepared KBA-NPs had a particle size of 152.6 nm with polydispersity index of 0.194, 79.7% entrapment efficiency and a cumulative 61.5% release of KBA from KBA-NPs, at 72 h. KBA-NPs showed 60.8% inhibition of rat paw oedema at 5 h as compared to 34.9% as that of KBA. The results of oral bioavailability study and in vivo anti-inflammatory activity showed 7- and 1.7-fold increase in bioavailability and anti-inflammatory activity, respectively, of KBA in KBA-NPs as compared to KBA alone.
CONCLUSION: The results of improved oral bioavailability and in vivo anti-inflammatory activity of KBA-NPs suggested successful development of KBA nanoparticle formulation.
Pharm Biol. 2016 Dec;54(12):2909-2916.
PMID: 27305832 [PubMed - indexed for MEDLINE]
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| 36. |
Comparative studies of pharmacokinetics and anticoagulatory effect in rats after oral administration of Frankincense and its processed products.
Pan YN, Liang XX, Niu LY, Wang YN, Tong X, Hua HM, Zheng J, Meng DY, Liu XQ
ETHNOPHARMACOLOGICAL RELEVANCE: Frankincense (FRA), Ruxiang, is the resin of Boswellia carterii Birdw and Boswellia bhaw-dajiana Birdw which has been used for centuries as formulas to improve the circulation and to relieve pain against carbuncles. Stir-fried Frankincense (SFF) and vinegar processed Frankincense (VPF) are two major processed Frankincense, and the processing procedures reportedly enhance the curative efficacy or reduce the side effects of FRA. This paper describes the comparisons in plasma pharmacokinetic behaviors of 11-keto-β-boswellic acid (KBA) and 3-acetyl-11-keto-β-boswellic acid (AKBA) in FRA and its processed products, and their effects on coagulation factors and blood clotting tetrachoric, using an acute cold blood-stasis animal model after oral administration of FRA, SFF, and VPF.
MATERIALS AND METHODS: For pharmacokinetic study, Sprague-Dawley (SD) rats were randomly divided into three groups, including group FRA, group SFF and group VPF. And the plasma samples were analyzed by HPLC. For study of anticoagulatory effect, SD rats were randomly divided into six groups, including control, acute cold blood-stasis model, Fu-fang-dan-shen tablet- (0.75g/kg), FRA-, SFF-, and VPF-treated (2.7g/kg) groups, respectively. The serum contents of thrombin-antithrombin complex (TAT), D-dimer (D-D), and prostacyclin (PGI2) of each group were measured by ELISA. The values of prothrombin time (PT), thrombin time (TT), activated partial thromboplastin time (APTT) and fibrinogen (FIB) were also assessed by hematology analyzer.
RESULTS: Significantly increased levels of Cmax, AUC, T1/2, and MRT were found in rats treated with the processed products. In addition, decreased levels of D-D and TAT and increased contents of PGI2 were observed in rats given FRA and its processed products, compared with that of the model group. Moreover, VPF improved anticoagulation more than SFF in the animals.
CONCLUSIONS: The observed improvement of anticoagulation by processed FRA may result from the increased absorption and bioavailability of triterpenoids.
J Ethnopharmacol. 2015 Aug;172():118-23.
PMID: 26117531 [PubMed - indexed for MEDLINE]
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| 37. |
Boswellia carterii liquisolid systems with promoted anti-inflammatory activity.
Mostafa DM, Ammar NM, Abd El-Alim SH, Kassem AA, Hussein RA, Awad G, El-Awdan SA
(BC) Birdwood oleogum resin is an ancient remedy of inflammation processes known since Ancient Egyptian time. Of boswellic acids, 3-acetyl-11-keto-β-boswellic acid (AKBA) is the most potent anti-inflammatory active principle. Liquisolid systems of the biologically active fraction of BC oleogum resin were prepared for improving dissolution properties using low dose oral delivery to achieve enhanced anti-inflammatory activity, in comparison with the standard oral anti-inflammatory; Indomethacin. AKBA was assayed, employing an accurate and sensitive HPLC method. Detection was carried out at 210 nm using UV/Vis detector. A solubility study for the bioactive fraction was conducted. Microcrystalline cellulose and Aeroperl®300 Pharma were used as carrier and coating materials. Angle of slide, liquid load factor and Carr's flow index were estimated. Six systems were prepared using polyethylene glycol 400, solvent and two drug loading concentrations; 20 and 40 %. For each concentration, three carrier: coat ratios were dispensed; 20:1, 10:1, and 5:1. Dissolution study was performed and two systems were selected for characterization and in vivo evaluation by investigating upper GIT ulcerogenic effect and anti-inflammatory efficacy in rats. Results indicate absence of ulcers and significantly higher and prolonged anti-inflammatory efficacy for formulations F1 and F2, with carrier: coat ratio, 5:1 and drug loads of 20 and 40 %, respectively, compared with standard oral indomethacin. We conclude higher efficacy of BC bioactive fraction liquisolids compared with Indomethacin with greater safety on GIT, longer duration of action and hence better patient compliance.
Curr Drug Deliv. 2015;12(4):454-63.
PMID: 25895614 [PubMed - indexed for MEDLINE]
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| 38. |
Acute and chronic toxicity, cytochrome p450 enzyme inhibition, and HERG channel blockade studies with a polyherbal, ayurvedic formulation for inflammation.
Dey D, Chaskar S, Athavale N, Chitre D
Ayurvedic plants are known for thousands of years to have anti-inflammatory and antiarthritic effect. We have recently shown that BV-9238, a proprietary formulation of Withania somnifera, Boswellia serrata, Zingiber officinale, and Curcuma longa, inhibits LPS-induced TNF-alpha and nitric oxide production from mouse macrophage and reduces inflammation in different animal models. To evaluate the safety parameters of BV-9238, we conducted a cytotoxicity study in RAW 264.7 cells (0.005-1 mg/mL) by MTT/formazan method, an acute single dose (2-10 g/kg bodyweight) toxicity study and a 180-day chronic study with 1 g and 2 g/kg bodyweight in Sprague Dawley rats. Some sedation, ptosis, and ataxia were observed for first 15-20 min in very high acute doses and hence not used for further chronic studies. At the end of 180 days, gross and histopathology, blood cell counts, liver and renal functions were all at normal levels. Further, a modest attempt was made to assess the effects of BV-9238 (0.5 µg/mL) on six major human cytochrome P450 enzymes and (3)H radioligand binding assay with human hERG receptors. BV-9238 did not show any significant inhibition of these enzymes at the tested dose. All these suggest that BV-9238 has potential as a safe and well tolerated anti-inflammatory formulation for future use.
Biomed Res Int. 2015;2015():971982.
PMID: 25893199 [PubMed - indexed for MEDLINE]
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| 39. |
Development and optimisation of 3-Acetyl-11-keto-β-boswellic acid loaded poly-lactic-co-glycolic acid-nanoparticles with enhanced oral bioavailability and in-vivo anti-inflammatory activity in rats.
Bairwa K, Jachak SM
OBJECTIVES: 3-Acetyl-11-keto-β-boswellic acid (AKBA) is a potent anti-inflammatory compound of Boswellia serrata. However, anti-inflammatory activity of AKBA is impeded by poor oral bioavailability due to its poor aqueous solubility. In this context, we aimed to develop poly lactic-co-glycolic acid (PLGA)-based nanoparticle formulation of AKBA (AKBA-NPs) in order to improve its oral bioavailability and in-vivo anti-inflammatory activity in rats.
METHODS: AKBA-NPs were prepared and characterised by analysing particle size and zeta potential using zeta sizer, surface morphology by scanning electron microscopy and transmission electron microscopy, and physical property using differential scanning calorimetry and X-ray diffraction techniques. The optimised nanoparticles were evaluated for in-vitro drug release and oral bioavailability studies, and in-vivo anti-inflammatory activity by carrageenan-induced rat paw oedema method.
KEY FINDINGS: The optimised AKBA-NPs showed the particle size of 179.6 nm with 0.276 polydispersity index and entrapment efficiency of 82.5%. AKBA-NPs showed increased in-vivo anti-inflammatory activity as compared with AKBA. Bioavailability study revealed about six times higher peak plasma concentration of AKBA in AKBA-NPs. Moreover, t1/2 and total area under the curve of AKBA were also enhanced by two and ninefold, respectively, in AKBA-NPs as compared with corresponding AKBA.
CONCLUSIONS: The promising results of improved oral bioavailability and in-vivo anti-inflammatory activity of AKBA suggested the successful nanoparticle formulation of AKBA.
J Pharm Pharmacol. 2015 Sep;67(9):1188-97.
PMID: 25851251 [PubMed - indexed for MEDLINE]
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| 40. |
Prospects of boswellic acids as potential pharmaceutics.
Du Z, Liu Z, Ning Z, Liu Y, Song Z, Wang C, Lu A
Boswellic acids have long been considered the main bioactive components of frankincense, and many studies in vitro and in animals as well as several clinical studies have confirmed their various bioactivities. In particular, a large number of mechanistic studies have confirmed their anti-inflammatory and antitumor activities. However, not every boswellic acid exhibits a satisfactory pharmacological performance, which depends on the chemical structure and functional groups of the acid. To enhance the pharmacological values of boswellic acids, derivatization has been specifically applied with the aim of discovering more active derivatives of BAs. In addition, the preliminary pharmacokinetic studies of these compounds using various standard methods show their poor bioavailability in humans and rodents, which has led to questions of their pharmacological relevance and potentially limits their use in clinical practice and pharmaceutical development. To improve these effects, some approaches have shown some improvements in effectiveness, and the new formula compatibility approach is considered a very reasonable method for improving the bioavailability of boswellic acids.
Planta Med. 2015 Mar;81(4):259-71.
PMID: 25714728 [PubMed - indexed for MEDLINE]
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| 41. |
Comparative pharmacokinetic study of two boswellic acids in normal and arthritic rat plasma after oral administration of Boswellia serrata extract or Huo Luo Xiao Ling Dan by LC-MS.
Wang H, Zhang C, Wu Y, Ai Y, Lee DY, Dai R
Huo Luo Xiao Ling Dan (HLXLD), a Chinese herbal formula composed of 11 different herbs, has been used traditionally for the treatment of arthritis and other chronic inflammatory diseases. However, the pharmacokinetic profile of its anti-inflammatory bioactive compounds has not been elucidated. Boswellic acids are the bioactive compounds with potent anti-inflammatory activity isolated from Boswellia serrate which is one of the 11 herbs of HLXLD. The objective of the study was to compare the pharmacokinetics of the two bioactive bowsellic acids: 11-keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic following oral administration of HLXLD or Boswellia serrata extract alone in normal and arthritic rats. An LC-MS method was developed and validated for the determination of 11-keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic in the comparative pharmacokinetic study. The results showed that there were significant differences in pharmacokinetic parameters between normal and arthritic groups. Interestingly, the absorptions of two boswellic acids were significantly higher in HLXLD than Boswellia serrata extract alone, indicating the synergistic effect of other herbal ingredients in HLXLD. This comparative pharmacokinetic study provided direct evidence supporting the notion that the efficacy of a complex mixture such as HLXLD is better than that of single components in treating human diseases.
Biomed Chromatogr. 2014 Oct;28(10):1402-8.
PMID: 24806456 [PubMed - indexed for MEDLINE]
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| 42. |
Transdermal microemulsions of Boswellia carterii Bird: formulation, characterization and in vivo evaluation of anti-inflammatory activity.
Mostafa DM, Ammar NM, Basha M, Hussein RA, El Awdan S, Awad G
CONTEXT: Boswellia species are trees (family: Bruseraceae) found in India, Northern Africa and the Middle East.
OBJECTIVE: This study aims at formulating low dose biologically active fraction from the oleogum resin of Boswellia carterii (BC) in transdermal (TD) microemulsions (MEs) to acquire promoted anti-inflammatory efficacy.
MATERIALS AND METHODS: The bioactive fraction of the oleogum resin of BC was tested for solubility in different components. The most efficient were selected for constructing phase diagrams for ME preparation. The bioactive fraction was assayed by high performance liquid chromatography for 3-acetyl-11-keto-β-boswellic acid (AKBA), at 210 nm. The bioactive fraction was incorporated in 6 MEs. ME systems were evaluated for drug content and optimized systems were tested for characterization, permeation, skin irritancy and in vivo evaluation of anti-inflammatory activity.
RESULTS AND DISCUSSION: Two systems were selected; ME1 and ME4 composed of Tween 80: PEG 400 at 1:1 and 2:1 ratio, with oil content 7.78 and 17.5%, respectively. The systems showed high encapsulation efficiency >83%, small droplet size <100 nm, and suitable pH for topical application. Permeation parameters for ME1 were higher compared to ME4. Both MEs were non irritant. ME1 showed significantly higher anti-inflammatory activity versus the standard TD anti-inflammatory piroxicam.
CONCLUSIONS: Optimized TD BC MEs could be used as a safe, effective and long acting alternative to oral anti-inflammatories, providing higher and prolonged efficacy and better patient compliance.
Drug Deliv. 2015;22(6):748-56.
PMID: 24725029 [PubMed - indexed for MEDLINE]
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| 43. |
Interference of boswellic acids with the ligand binding domain of the glucocorticoid receptor.
Scior T, Verhoff M, Gutierrez-Aztatzi I, Ammon HP, Laufer S, Werz O
Boswellic acids (BAs) possess anti-inflammatory properties in various biological models with similar features to those of glucocorticoids (GCs), such as suppression of the release of pro-inflammatory cytokines. Hence, the molecular mechanism of BAs responsible for their anti-inflammatory features might be attributable to interference with the human glucocorticoid receptor (GR). Due to obvious structural similarities with GCs, we conducted pharmacophore studies as well as molecular docking simulations of BAs as putative ligands at the ligand binding site (LBS) of the GR in distinct functional states. In order to verify receptor binding and functional activation of the GR by BAs, radiometric binding assays as well as GR response element-dependent luciferase reporter assay were performed with dexamethasone (DEX) as a functional positive control. With respect to the observed position of GCs in GR crystal complexes in the active antagonist state, BAs docked in a flipped orientation with estimated binding constants reflecting nanomolar affinities. For validation, DEX and other steroids were successfully redocked into their crystal poses in similar ranges as reported in the literature. In line with the pharmacophore and docking models, the BAs were strong GR binders (radiometric binding assay), albeit none of the BAs activated the GR in the reporter gene assay, when compared to the GC agonist DEX. The flipped scaffolds of all BAs dislodge the known C-11 function from its receiving amino acid (Asn564), which may explain the silencing effects of receptor-bound BAs in the reporter gene assay. Together, our results constitute a compelling example of rigid keys acting in an adaptable lock qualifying as a reversed induced fit mechanism, thereby extending the hitherto published knowledge about molecular target interactions of BAs.
J Chem Inf Model. 2014 Mar;54(3):978-86.
PMID: 24512031 [PubMed - indexed for MEDLINE]
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| 44. |
Investigating permeability related hurdles in oral delivery of 11-keto-β-boswellic acid.
Bagul P, Khomane KS, Bansal AK
11-Keto-β-boswellic acid (KBA) is an important and potent boswellic acids responsible for anti-inflammatory action of Boswellia extract. However, its pharmaceutical development has been severely limited by its poor oral bioavailability. The present work aims to investigate the permeability related hurdles in oral delivery of KBA. Gastrointestinal stability, gastrointestinal metabolism, adsorption-desorption kinetics and Caco-2 permeability studies have been carried out. KBA was found poorly permeable with Papp value of 2.85 ± 0.14 × 10(-6)cm/s. Higher absorptive transport indicated role of carrier mediated transport. Moreover, KBA transport across monolayer showed saturation kinetics at higher concentrations. KBA exposed to 1α,25-(OH)2 vitamin D3 treated cell monolayer showed the lowest Papp value of 2.01×10(-6) ± 0.02 × 10(-6)cm/s indicating role of CYP3A4 mediated metabolism during KBA transport. Metabolic stability experiments in jejunum S9 fractions further confirmed this. KBA was found unstable in simulated gastrointestinal fluids and also got accumulated in the enterocytes. Sorption and desorption kinetic studies using Caco-2 cells further confirmed accumulation of KBA inside the enterocytes. KBA also showed pH dependent permeability with higher flux at gradient pH condition of pH 6.5 at apical and 7.4 at basolateral. Taken as whole, the major permeability related hurdles that hampered oral bioavailability of KBA included its gastrointestinal instability, CYP3A4 mediated intestinal metabolism, accumulation within the enterocytes and saturable kinetics. The present investigation may help in designing novel drug delivery system for KBA.
Int J Pharm. 2014 Apr;464(1-2):104-10.
PMID: 24463070 [PubMed - indexed for MEDLINE]
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| 45. |
Microbial transformation of acetyl-11-keto-boswellic acid by Cunninghamella elegans.
Xin XL, Huo H, Chen L, Li J, Sun JH, Zheng PW, Sun Y, Wu ZM, Xiong YH
Microbial biotransformation of acetyl-11-keto-boswellic acid by Cunninghamella elegans AS 3.1207 was carried out, and totally four transformed products were isolated. On the basis of the extensive spectral data, their structures were characterized as 7β-hydroxy-11-keto-boswellic acid (1), 7β,30-dihydroxy-11-keto-boswellic acid (2), 7β,16α-dihydroxy-3-acetyl-11-keto-boswellic acid (3), and 7β,15α,21β-trihydroxy-3-acetyl-11-keto-boswellic acid (4), respectively. Among them, products 1 and 2 are the new compounds.
J Asian Nat Prod Res. 2013 Nov;15(11):1173-8.
PMID: 24168329 [PubMed - indexed for MEDLINE]
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| 46. |
Biotransformation of 11-keto-β-boswellic acid by Cunninghamella blakesleana.
Wang Y, Sun Y, Wang C, Huo X, Liu P, Wang C, Zhang B, Zhan L, Zhang H, Deng S, Zhao Y, Ma X
11-Keto-β-boswellic acid (KBA), as one of the active constituents in the gum resin of Boswellia serrata, possesses significant biological activities including anti-inflammatory activity. However, its extensive metabolism and low polarity has limited the systemic availability of KBA. The present research was aimed to obtain and explore the various possible derivatives of KBA through biotransformation by Cunninghamella blakesleana AS 3.970. A total of ten transformed compounds were isolated and purified, and their chemical structures were characterized as 7β-hydroxy-11-keto-β-boswellic acid; 7β, 15α-dihydroxy-11-keto-β-boswellic acid ; 7β, 16β-dihydroxy-11-keto-β-boswellic acid; 7β, 16α-dihydroxy-11-keto-β-boswellic acid; 7β, 22β-dihydroxy-11-keto-β-boswellic acid; 7β, 21β-dihydroxy-11-keto-β-boswellic acid; 7β, 20β-dihydroxy-11-keto-β-boswellic acid; 7β, 30-dihydroxy-11-keto-β-boswellic acid; 3α, 7β-dihydroxy-11-oxours-12-ene-24, 30-dioic acid and 3α, 7β-dihydroxy-30-(2-hydroxypropanoyloxy)-11-oxours-12-en-24-oic acid by various spectroscopic methods. The biotransformation processes include hydroxylation, oxidation and esterification. Primary structure-activity relationships (SAR) of inhibitory effects on NO production in RAW 264.7 macrophage cells are discussed.
Phytochemistry. 2013 Dec;96():330-6.
PMID: 23962801 [PubMed - indexed for MEDLINE]
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| 47. |
A new cytochrome P450 system from Bacillus megaterium DSM319 for the hydroxylation of 11-keto-β-boswellic acid (KBA).
Brill E, Hannemann F, Zapp J, Brüning G, Jauch J, Bernhardt R
In the genome of Bacillus megaterium DSM319, a strain who has recently been sequenced to fully exploit its potential for biotechnological purposes, we identified a gene encoding the cytochrome P450 CYP106A1 as well as genes encoding potential redox partners of CYP106A1. We cloned, expressed, and purified CYP106A1 and five potential autologous redox partners, one flavodoxin and four ferredoxins. The flavodoxin and three ferredoxins were able to support the activity of CYP106A1 displaying the first cloned natural redox partners of a cytochrome P450 from B. megaterium. The CYP106A1 system was able to convert the pentacyclic triterpene 11-keto-β-boswellic acid (KBA) belonging to the main bioactive constituents of Boswellia serrata gum resin extracts, which are used to treat inflammatory disorders and arthritic diseases. In order to provide sufficient amounts of the KBA products to characterize them structurally by NMR spectroscopy, recombinant whole-cell biocatalysts were constructed based on B. megaterium MS941. The main product has been identified as 7β-hydroxy-KBA, while the side product (∼20%) was shown to be a mixture of 7β,15α-dihydroxy-KBA and 15α-hydroxy-KBA. Without further optimization 560.7 mg l⁻¹ day⁻¹ of the main product, 7β-hydroxy-KBA, could be obtained thus providing a suitable starting point for the efficient production of modified KBA by chemical tailoring to produce novel KBA derivatives with increased bioavailability and this way more efficient drugs.
Appl Microbiol Biotechnol. 2014 Feb;98(4):1701-17.
PMID: 23797329 [PubMed - indexed for MEDLINE]
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| 48. |
Synthesis and pharmacokinetic profile of rhein- boswellic acid conjugate.
Suneela D, Dipmala P
Rhein, an active metabolite of diacerein, down-regulates the gene-expression and production of pro-matrix metalloproteinases and up-regulates the tissue inhibitors of metalloproteinase-1 production. The therapeutic effects of diacerein on osteoarthritis are, at least in part, due to the chondroprotective effect of rhein. Boswellic acid is a specific, non-redox inhibitor of leukotriene synthesis. It is claimed to possess good anti-inflammatory, anti-arthritic, analgesic, and anti-ulcer activities. It prevents the destruction of articular cartilage by decreasing degradation of glycosaminoglycans. Therefore, rhein and boswellic acid were linked chemically through a bioreversible ester linkage to synthesize their mutual prodrug by reported procedure. In vitro release profile of this prodrug was extensively studied in aqueous buffers of varied pH, upper GIT homogenates and 80% human plasma. In vivo release studies were undertaken in blood, urine and feces of rats. The prodrug was stable in HCl buffer (pH 1.2) and stomach homogenates of rats. However; in phosphate buffer (pH 7.4) and in intestinal homogenates the prodrug exhibited 91% and 96% release of rhein and 27.5% and 38% release of boswellic acid respectively over a period of 6h following first order kinetics. In 80% human plasma (in vitro) and rat blood (in vivo) also 96.35% and 91% release of rhein and 78% and 86.41% release of boswellic acid respectively was observed. The 24 h pooled samples of rat urine revealed presence of 6.2% intact prodrug, 7.1% of rhein and 8.9% of boswellic acid indicating their renal excretion. Samples of rat feces pooled over a period of 24 h showed absence of rhein and presence of 3.1% of intact boswellic acid and 4.6% of boswellic acid emphasizing their intestinal excretion. The in vivo release kinetics of prodrug in rat clearly indicated activation of prodrug to be occurring in blood, being catalyzed by the weak alkaline pH of blood (7.4) in combination with esterases present therein.
Bioorg Med Chem Lett. 2012 Dec;22(24):7582-7.
PMID: 23107483 [PubMed - indexed for MEDLINE]
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| 49. |
In vitro metabolism, permeation, and brain availability of six major boswellic acids from Boswellia serrata gum resins.
Gerbeth K, Hüsch J, Fricker G, Werz O, Schubert-Zsilavecz M, Abdel-Tawab M
Boswellia serrata gum resin extracts (BSE) revealed potent anti-inflammatory actions in preclinical and clinical studies. In 2002 BSE was assigned an orphan drug status by the European Medicines Agency (EMA) for the treatment of peritumoral edema. In the past pharmacological effects of BSE were mainly attributed to 11-keto-β-boswellic acid (KBA) and 3-acetyl-11-keto-β-boswellic acid (AKBA). Therefore pharmacokinetic and pharmacodynamic studies focused mainly on these two boswellic acids (BAs). However, other BAs, like β-boswellic acid (βBA), might also contribute to the anti-inflammatory actions of BSE. Here, we determined the metabolic stability, permeability and brain availability of six major BAs, that is, KBA, AKBA, βBA, 3-acetyl-β-boswellic acid (AβBA), α-boswellic acid (αBA), and 3-acetyl-α-boswellic acid (AαBA). For permeability studies, the Caco-2 model was adapted to physiological conditions by the addition of bovine serum albumin (BSA) to the basolateral side and the use of modified fasted state simulated intestinal fluid (FaSSIF) on the apical side. Under these conditions the four BAs lacking the 11-keto moiety revealed moderate permeability. Furthermore the permeability of AKBA and KBA was improved compared to earlier studies. In contrast to Aα- and AβBA, βBA and αBA were intensively metabolized after incubation with human and rat liver microsomes. Finally, the availability of all six major BAs could be confirmed in rat brain 8h after oral administration of 240mg/kg BSE to rats showing mean concentrations of 11.6ng/g for KBA, 37.5ng/g for AKBA, 485.1ng/g for αBA, 1066.6ng/g for βBA, 43.0ng/g for AαBA and 163.7ng/g for AβBA.
Fitoterapia. 2013 Jan;84():99-106.
PMID: 23103296 [PubMed - indexed for MEDLINE]
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| 50. |
Enhanced absorption of boswellic acids by a lecithin delivery form (Phytosome(®)) of Boswellia extract.
Hüsch J, Bohnet J, Fricker G, Skarke C, Artaria C, Appendino G, Schubert-Zsilavecz M, Abdel-Tawab M
The anti-inflammatory potential of Boswellia serrata gum resin extracts has been demonstrated in vitro and in animal studies as well as in pilot clinical trials. However, pharmacokinetic studies have evidenced low systemic absorption of boswellic acids (BAs), especially of KBA and AKBA, in rodents and humans. This observation has provided a rationale to improve the formulation of Boswellia extract. We present here the results of a murine comparative bioavailability study of Casperome™, a soy lecithin formulation of standardized B. serrata gum resin extract (BE), and its corresponding non-formulated extract. The concentration of the six major BAs [11-keto-β-boswellic acid (KBA), acetyl-11-keto-β-boswellic acid (AKBA), β-boswellic acid (βBA), acetyl-β-boswellic acid (AβBA), α-boswellic acid (αBA), and acetyl-α-boswellic acid (AαBA)] was evaluated in the plasma and in a series of tissues (brain, muscle, eye, liver and kidney), providing the first data on tissue distribution of BAs. Weight equivalent and equimolar oral administration of Casperome™ provided significantly higher plasma levels (up to 7-fold for KBA, and 3-fold for βBA quantified as area under the plasma concentration time curve, AUC(last)) compared to the non-formulated extract. This was accompanied by remarkably higher tissue levels. Of particular relevance was the marked increase in brain concentration of KBA and AKBA (35-fold) as well as βBA (3-fold) following Casperome™ administration. Notably, up to 17 times higher BA levels were observed in poorly vascularized organs such as the eye. The increased systemic availability of BAs and the improved tissue distribution, qualify Casperome™ for further clinical development to fully exploit the clinical potential of BE.
Fitoterapia. 2013 Jan;84():89-98.
PMID: 23092618 [PubMed - indexed for MEDLINE]
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| 51. |
Effect of phospholipid-based formulations of Boswellia serrata extract on the solubility, permeability, and absorption of the individual boswellic acid constituents present.
Hüsch J, Gerbeth K, Fricker G, Setzer C, Zirkel J, Rebmann H, Schubert-Zsilavecz M, Abdel-Tawab M
Boswellia serrata gum resin extracts are used widely for the treatment of inflammatory diseases. However, very low concentrations in the plasma and brain were observed for the boswellic acids (1-6, the active constituents of B. serrata). The present study investigated the effect of phospholipids alone and in combination with common co-surfactants (e.g., Tween 80, vitamin E-TPGS, pluronic f127) on the solubility of 1-6 in physiologically relevant media and on the permeability in the Caco-2 cell model. Because of the high lipophilicity of 1-6, the permeability experiments were adapted to physiological conditions using modified fasted state simulated intestinal fluid as apical (donor) medium and 4% bovine serum albumin in the basolateral (receiver) compartment. A formulation composed of extract/phospholipid/pluronic f127 (1:1:1 w/w/w) increased the solubility of 1-6 up to 54 times compared with the nonformulated extract and exhibited the highest mass net flux in the permeability tests. The oral administration of this formulation to rats (240 mg/kg) resulted in 26 and 14 times higher plasma levels for 11-keto-β-boswellic acid (1) and acetyl-11-keto-β-boswellic acid (2), respectively. In the brain, five times higher levels for 2 compared to the nonformulated extract were determined 8 h after oral administration.
J Nat Prod. 2012 Oct;75(10):1675-82.
PMID: 23013292 [PubMed - indexed for MEDLINE]
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| 52. |
[Does a positive finding of tetrahydrocannabinol in the blood result from ingestion of Indian frankincense (Boswellia serrata)?].
Skopp G, Schmitt G
The exculpatory statement that a positive THC finding in the blood is due to the consumption of hemp products or passive exposure to cannabis smoke has been disproved by the monitoring of hemp products and recent passive inhalation studies conducted in social settings, which showed that these conditions are unlikely to produce a positive result in the blood. The defense that the ingestion of Indian olibanum may result in a positive THC concentration in the blood is unusual; it is based on older publications where authors had speculated on a possible association of the synthetic pathways of THC from terpenoid precursors also being present in olibanum and the biogenesis of THC in hemp. It had further been speculated whether chemical or plant-derived pathways may also occur in humans. A thorough understanding of the different pathways and recently published results have outdated these speculations.
Arch Kriminol. 2012;229(5-6):154-62.
PMID: 22834359 [PubMed - indexed for MEDLINE]
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| 53. |
Bioavailability, distribution, and antioxidative effects of selected triterpenes in mice.
Yin MC, Lin MC, Mong MC, Lin CY
This study analyzed the content of eight triterpenes (oleanolic acid, ursolic acid, arjunolic acid, asiatic acid, boswellic acid, corosolic acid, madecassic acid, and maslinic acid) in ten vegetables and eight fruits. These compounds at 0.5% were supplied to mice for 4 or 8 weeks. The bioavailability, tissue distribution, and antioxidative protection of these triterpenes were examined. Results showed that triterpenes were detected in eight vegetables and six fruits. Basil and brown mustard contained seven test triterpenes, in the range of 14-102 mg/100 g dry weight. The level of each triterpene in plasma, brain, heart, liver, kidney, colon, and bladder increased as the feeding period was increased from 4 weeks to 8 weeks (P < 0.05). Renal homogenates from mice with triterpene intake had greater antioxidative effects against glucose-induced glutathione loss and malondialdehyde and oxidized glutathione production when compared with those from control groups (P < 0.05). These data support that these triterpenes were absorbed and deposited in their intact forms, which in turn exerted in vivo antioxidative protection.
J Agric Food Chem. 2012 Aug;60(31):7697-701.
PMID: 22816768 [PubMed - indexed for MEDLINE]
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| 54. |
Hydroxylation of the triterpenoid dipterocarpol with CYP106A2 from Bacillus megaterium.
Schmitz D, Zapp J, Bernhardt R
The bacterial steroid-hydroxylase CYP106A2 from Bacillus megaterium ATCC 13368 hydroxylates a variety of 3-oxo-Δ-4-steroids and has recently been shown to catalyse regioselective hydroxylation of the diterpene abietic acid, as well as the pentacyclic triterpene 11-keto-β-boswellic acid. The broad substrate spectrum of this enzyme makes it an excellent candidate for biotechnological application. Because the natural substrate of this enzyme is not known, we assumed that the whole substrate spectrum might not yet be fully discovered. The difference spectroscopy method was used to screen a natural product library of 502 compounds. Screening of the library resulted in the identification of twelve hits, among them eight potential and four known substrates for CYP106A2. Interestingly, when testing the potential substrates, product formation was obtained only with triterpenes, namely dipterocarpol and betulin. Dipterocarpol is the most promising compound for biotechnological application because it is a dammarane-type triterpenoid, as are the major bioactive compounds of ginseng. The dipterocarpol hydroxylation products were analysed by NMR and identified as 7β-hydroxydipterocarpol and 7β,11α-dihydroxydipterocarpol. To investigate the putative bioactive properties of these novel compounds, in vitro cytotoxicity assays with HeLa and COS-1 cells were performed. The substrate dipterocarpol and the dihydroxylated product did not show cytotoxic activity in our study. By contrast, the 7β-hydroxylated product was found to be cytotoxic to both tested cell lines. This study highlights the potency of CYP106A2 as a versatile biocatalyst for the bioconversion of natural products into pharmaceutically relevant bioactive products.
FEBS J. 2012 May;279(9):1663-74.
PMID: 22269065 [PubMed - indexed for MEDLINE]
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| 55. |
Increased bioavailability of 11-keto-β-boswellic acid following single oral dose frankincense extract administration after a standardized meal in healthy male volunteers: modeling and simulation considerations for evaluating drug exposures.
Skarke C, Kuczka K, Tausch L, Werz O, Rossmanith T, Barrett JS, Harder S, Holtmeier W, Schwarz JA
J Clin Pharmacol. 2012 Oct;52(10):1592-600.
PMID: 22167571 [PubMed - indexed for MEDLINE]
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| 56. |
Determination of major boswellic acids in plasma by high-pressure liquid chromatography/mass spectrometry.
Gerbeth K, Meins J, Kirste S, Momm F, Schubert-Zsilavecz M, Abdel-Tawab M
Until now, dexamethasone is the medication of choice to reduce peritumoral edema associated with primary and secondary brain tumors. Because of the severe side effects accompanying such a treatment the interest in alternative agents that may be co-administered with glucocorticoids and help to reduce the required dose is constantly increasing. Boswellia serrata gum resin extracts (BSE), which have been designated an orphan drug status by the European Medicines Agency (EMA) in 2002 for the treatment of peritumoral edema, may represent a promising supplemental herbal remedy. However, clinical studies on the effect of BSE on brain edema as well as analyzes of serum levels are very scarce. Based on that background a prospective, placebo controlled, and double blind clinical pilot trial was conducted on 14 patients applying for the first time a high dose of 4200 mg BSE per day and 13 patients receiving placebo. For monitoring the serum levels of all major boswellic acids (BAs) a highly sensitive HPLC-MS method has been developed that allows the determination of KBA and AKBA from 5.0 ng/ml to 3000 ng/ml and of αBA, βBA, AαBA and AβBA from 0.5 ng/ml to 12,000 ng/ml. It is the first validated method that covers such a wide concentration range, which makes it suitable to be used as standard method in clinical trials as it compensates for the great pharmacokinetic variability in the plasma levels of BAs observed in clinical practice. Average steady concentrations (ng/ml) in the range of 6.4-247.5 for KBA, 0-15.5 for AKBA, 36.7-4830.1 for αBA, 87.0-11948.5 for βBA, 73.4-2985.8 for AαBA and 131.4-6131.3 for AβBA were determined in the verum group. The here quantified steady state levels suggest βBA to be a possible candidate for the anti-inflammatory and anti-edemateous effects of BSE. In general, the serum level analysis underlines the promising clinical results of BSE on cerebral edema.
J Pharm Biomed Anal. 2011 Dec;56(5):998-1005.
PMID: 21855244 [PubMed - indexed for MEDLINE]
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| 57. |
A new Bacillus megaterium whole-cell catalyst for the hydroxylation of the pentacyclic triterpene 11-keto-β-boswellic acid (KBA) based on a recombinant cytochrome P450 system.
Bleif S, Hannemann F, Zapp J, Hartmann D, Jauch J, Bernhardt R
The use of cytochromes P450 for the regio- and stereoselective hydroxylation of non-activated carbon atoms in biotechnological applications reflects an efficient and cost-effective alternative in comparison to classical organic chemistry. The prokaryotic cytochrome P450 CYP106A2 from Bacillus megaterium ATCC 13368 hydroxylates a variety of 3-oxo-Δ⁴ steroids and recently it was identified to carry out a one-step regioselective allylic hydroxylation of the diterpene abietic acid. The anti-inflammatory pentacyclic triterpene 11-keto-β-boswellic acid (KBA) was found to be a further substrate of CYP106A2, being the first report of a pentacyclic triterpene conversion by a prokaryotic P450. The reaction products were analyzed by HPLC and the corresponding kinetic parameters were investigated. Structure determination of the main product by NMR revealed a 15α-hydroxylation of this substrate. In order to overcome the inability of a recombinant P450 whole-cell system in E. coli for the uptake of acids with terpene structure, we developed for the first time an expression system for cytochromes P450 in B. megaterium (strains MS941 and ATCC 13368). Interestingly, CYP106A2 was only successfully expressed in the plasmid-less B. megaterium strain MS941 but not in ATCC13368. This recombinant system, with the co-expressed heterologous redox chain of the P450, bovine adrenodoxin reductase (AdR), and bovine adrenodoxin (Adx), was applied for the whole-cell conversion of KBA. The formation of 15α-hydroxy-KBA was increased 15-fold in comparison with the naturally CYP106A2-expressing B. megaterium strain ATCC 13368.
Appl Microbiol Biotechnol. 2012 Feb;93(3):1135-46.
PMID: 21779845 [PubMed - indexed for MEDLINE]
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| 58. |
Complexation with phosphatidyl choline as a strategy for absorption enhancement of boswellic acid.
Sharma A, Gupta NK, Dixit VK
Boswellic acids (BAs) are isolated from oleo gum resin of Boswellia serrata and are reported to be effective as anti-inflammatory, hypolipidemic, immunomodulatory, and anti-tumor. Pharmacokinetic studies of boswellic acid reveal its poor absorption through the intestine. The objective of the present study is to enhance bioavailability of boswellic acid by its complexation with phosphatidylcholine. A complex of boswellic acid was prepared with phosphatidylcholine and characterized on the basis of solubility, melting point, TLC, and IR. An everted intestine sac technique was used to study ex-vivo drug absorption of boswellic acid-phosphatidylcholine (BA-PC) complex and plain boswellic acid. Anti-inflammatory activity of the complex was compared with boswellic acid in carrageenan-induced paw edema in rats. Hypolipidemic activity was also evaluated in Triton-induced hyperlipidemia. The complex was also converted into vesicles (phytosomes) and compared with other vesicular systems (liposomes and niosomes) by evaluating its anti-inflammatory effect. Analytical reports along with spectroscopic data revealed the formation of a complex. The results of ex-vivo study show that BA-PC complex has significantly increased absorption compared with boswellic acid, when given in equimolar doses. The complex showed better anti-inflammatory and hypolipidemic activity as compared to BA. Among all vesicular systems phytosomes showed maximum anti-inflammatory activity. Enhanced bioavailability of the BA-PC complex may be due to the amphiphilic nature of the complex, which greatly enhance the water and lipid solubility of the boswellic acid. The present study clearly indicates the superiority of complex over boswellic acid, in terms of better absorption, enhanced bioavailability and improved pharmacokinetics.
Drug Deliv. 2010 Nov;17(8):587-95.
PMID: 20624027 [PubMed - indexed for MEDLINE]
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| 59. |
3-Acetyl-11-keto-beta-boswellic acid loaded-polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity.
Goel A, Ahmad FJ, Singh RM, Singh GN
OBJECTIVES: The aim of this study was to develop 3-acetyl-11-keto-beta-boswellic acid (AKBA)-loaded polymeric nanomicelles for topical anti-inflammatory and anti-arthritic activity.
METHODS: Polymeric nanomicelles of AKBA were developed by a radical polymerization method using N-isopropylacrylamide, vinylpyrrolidone and acrylic acid. The polymeric nanomicelles obtained were characterized by Fourier transform infrared (FTIR), transmission electron microscopy (TEM) and dynamic light scattering (DLS). In-vitro and in-vivo evaluations of AKBA polymeric nanomicelles gel were carried out for enhanced skin permeability and anti-inflammatory and anti-arthritic activity.
KEY FINDINGS: TEM and DLS results demonstrated that polymeric nanomicelles were spherical with a mean diameter approximately 45 nm. FTIR data indicated a weak interaction between polymer and AKBA in the encapsulated system. The release of drug in aqueous buffer (pH 7.4) from the polymeric nanomicelles was 23 and 55% after 2 and 8 h, respectively, indicating sustained release. In-vitro skin permeation studies through excised abdominal skin indicated a threefold increase in skin permeability compared with AKBA gel containing the same amount of AKBA as the AKBA polymeric nanomicelles gel. The AKBA polymeric nanomicelle gel showed significantly enhanced anti-inflammatory and anti-arthritic activity compared with the AKBA gel.
CONCLUSIONS: This study suggested that AKBA polymeric nanomicelle gel significantly enhanced skin permeability, and anti-inflammatory and anti-arthritic activity.
J Pharm Pharmacol. 2010 Feb;62(2):273-8.
PMID: 20487208 [PubMed - indexed for MEDLINE]
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| 60. |
Permeation of Boswellia extract in the Caco-2 model and possible interactions of its constituents KBA and AKBA with OATP1B3 and MRP2.
Krüger P, Kanzer J, Hummel J, Fricker G, Schubert-Zsilavecz M, Abdel-Tawab M
Traditionally Boswellia serrata extract is used in the Indian Ayurvedic medicine for the treatment of inflammatory diseases. In 2002 the EMEA designated Boswellia an orphan drug status for the treatment of peritumoral oedema. Pharmacokinetic studies yielded low plasma concentrations of the active ingredients 11-keto-beta-boswellic acid (KBA) and 3-acetyl-11-keto-beta-boswellic acid (AKBA). In continuation of the tests investigating the factors limiting bioavailability of boswellic acids, the present study examined the permeability of KBA and AKBA in human Caco-2 cell lines. In addition, the interaction of KBA and AKBA with the organic anion transporter OATP1B3 and the multi drug resistant proteins P-glycoprotein and MRP2 was evaluated using partly fluorescent-based assays. The permeability studies revealed poor permeability of AKBA and moderate absorption of KBA with a P(app) value of 1.69 x 10(-6) cm/s. Most of KBA and AKBA were found to be retained by the Caco-2 monolayer. Neither KBA nor AKBA could be identified as substrates of P-glycoprotein. However, both KBA and AKBA modulated the activity of OATP1B3 and MRP2, indicating that therapeutic relevant interactions with other anionic drugs may be expected. The results of the present study provide the first explanation for the pharmacokinetic properties of KBA and AKBA.
Eur J Pharm Sci. 2009 Feb;36(2-3):275-84.
PMID: 19010411 [PubMed - indexed for MEDLINE]
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| 61. |
Metabolism of boswellic acids in vitro and in vivo.
Krüger P, Daneshfar R, Eckert GP, Klein J, Volmer DA, Bahr U, Müller WE, Karas M, Schubert-Zsilavecz M, Abdel-Tawab M
Boswellia serrata resin dry extract is among the few herbal remedies designated with an orphan drug status for the treatment of peritumoral brain edema. In addition, boswellic acids (BAs), the main active ingredients of B. serrata extracts, have potent anti-inflammatory properties, and may represent promising agents for the treatment of inflammatory diseases. Pharmacokinetic studies, however, revealed poor bioavailability, especially of 11-keto-beta-boswellic acid (KBA) and 3-acetyl-11-keto-beta-boswellic acid (AKBA), the most potent BAs. To address the question of whether BAs are extensively metabolized, we determined the metabolic stability of KBA and AKBA in vitro, investigated the in vitro metabolism of BAs, and compared the metabolic profiles of KBA and AKBA with those obtained in rats in vivo. In rat liver microsomes and hepatocytes as well as in human liver microsomes, we found that KBA but not AKBA undergoes extensive phase I metabolism. Oxidation to hydroxylated metabolites is the principal metabolic route. In vitro, KBA yielded metabolic profiles similar to those obtained in vivo in rat plasma and liver, whereas no metabolites of AKBA could be identified in vivo. Furthermore, AKBA is not deacetylated to KBA. This study indicates that the efficacy of B. serrata extract may be enhanced by increasing the bioavailability of AKBA.
Drug Metab Dispos. 2008 Jun;36(6):1135-42.
PMID: 18356270 [PubMed - indexed for MEDLINE]
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| 62. |
Compression coated systems for colonic delivery of 5-fluorouracil.
Sinha VR, Singh A, Singh S, Bhinge JR
Compression coating is one of the approaches for delaying the release of drugs. The aim of this study was to develop colon-specific compression coated systems of 5-fluorouracil (5-FU) for the treatment of colorectal cancer using xanthan gum, boswellia gum and hydroxypropyl methylcellulose (HPMC) as the coating materials. Core tablets containing 50 mg of 5-FU were prepared by direct compression. The coating of the core tablets was done using different coat weights (230, 250, 275 and 300 mg) and different ratios (1:2, 2:1, 1:3, 1:7 and 3:4) of boswellia gum and xanthan gum and different ratios (1:1, 1:2, 2:1, and 2:3) of boswellia gum and HPMC. In-vitro release studies were carried out using simulated gastric and intestinal fluids, with and without rat caecal contents. Among the different ratios used for coating with boswellia:xanthan gum combination, ratio 1:3 gave the best release profile with the lowest coating weights of 230 mg (7.47 +/- 1.56% in initial 5 h). Further increase in the coat weights to 250, 275 and 300 mg led to drug release of 5.63 +/- 0.53%, 5.09 +/- 1.56% and 4.57 +/- 0.88%, respectively, in the initial 5 h and 96.90 +/- 0.66%, 85.05 +/- 1.01% and 80.22 +/- 0.35%, respectively, in 24 h. When coating was carried out using different ratios of the combination boswellia gum and HPMC, the ratio 2:3 gave the best results among the initial trial batches (7.80 +/- 0.57% in 5 h). Increasing the coat weights to 250, 275 and 300 mg led to drug release of 6.5 +/- 0.27%, 3.70 +/- 2.3% and 2.99 +/- 0.72%, respectively, in the initial 5 h and 96.90 +/- 0.66%, 85.05 +/- 1.01% and 80.22 +/- 0.35%, respectively, in 24 h. In-vitro studies were further carried out in the presence of 2% w/v rat caecal contents, which led to complete release of the drug from the tablets. Therefore, this study lays a basis for use of compression coating of 5-FU as a tool for delaying the release of the drug, which ensures better clinical management of the disease.
J Pharm Pharmacol. 2007 Mar;59(3):359-65.
PMID: 17331338 [PubMed - indexed for MEDLINE]
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| 63. |
Estimation of boswellic acids from market formulations of Boswellia serrata extract and 11-keto beta-boswellic acid in human plasma by high-performance thin-layer chromatography.
Shah SA, Rathod IS, Suhagia BN, Patel DA, Parmar VK, Shah BK, Vaishnavi VM
A rapid and sensitive high-performance thin-layer chromatographic (HPTLC) method was developed and validated for the quantitative estimation of boswellic acids in formulation containing Boswellia serrata extract (BSE) and 11-keto beta-boswellic acid in human plasma. Simple extraction method was used for isolation of boswellic acid from formulation sample and acidified plasma sample. The isolated samples were chromatographed on silica gel 60F(254)-TLC plates, developed using ternary-solvent system (hexane-chloroform-methanol, 5:5:0.5, v/v) and scanned at 260 nm. The linearity range for 11-KBA spiked in 1 ml of plasma was 29.15-145.75 ng with average recovery of 91.66%. The limit of detection and limit of quantification for 11-KBA in human plasma were found to be 8.75 ng/ml and 29.15 ng/ml. The developed method was successfully applied for the assay of market formulations containing BSE and to determine plasma level of 11-keto beta-boswellic acid in a clinical pilot study.
J Chromatogr B Analyt Technol Biomed Life Sci. 2007 Apr;848(2):232-8.
PMID: 17101304 [PubMed - indexed for MEDLINE]
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| 64. |
Modulation of Pgp function by boswellic acids.
Weber CC, Reising K, Müller WE, Schubert-Zsilavecz M, Abdel-Tawab M
Boswellic acids, the main active ingredients of Boswellia serrata, are gaining more and more importance in the treatment of peritumoural oedema and chronic inflammatory diseases. They may be even considered as alternative drugs to corticosteroids in reducing cerebral peritumoural oedema. An important focus for drugs acting in the central nervous system is achieving a high extent of brain penetration. Today there is increasing evidence for the importance of transporters, especially P-glycoprotein (Pgp), for drug disposition and resulting clinical response. Pharmacokinetic studies revealed that the concentrations of the potent keto derivatives, the 11-keto-beta-boswellic acid (KBA) and the acetyl-11-keto-beta-boswellic acid (AKBA), in proportion to boswellic acids lacking a keto group, like the beta-boswellic acid, are much lower in plasma than in the orally administered extract. Moreover the brain/plasma ratio for KBA and AKBA determined in preliminary experiments on rats was only about 0.51 and 0.81, respectively, in spite of their lipophilicity. Until now little is known about the cerebral pharmacokinetics of boswellic acids and how it may be influenced. Since many drugs are known to interact with Pgp at the level of the intestine and the blood-brain barrier the modulatory potencies of the Boswellia serrata extract of H15(R) and the major boswellic acids on the transport activity of Pgp have been determined in two in vitro assays. A human lymphocytic leukaemia cell line (VLB cells) expressing Pgp was chosen as model for human Pgp, and porcine brain capillary endothelial cells (PBCEC cells) were taken as model for the blood-brain barrier using calcein acetoxymethyl ester (calcein-AM) as Pgp substrate. It was found that the Boswellia extract, as well as the keto-boswellic acids inhibit the transport activity of Pgp in the micromolecular range in both cell types. No modulation was observed using those boswellic acids which have no keto group in their structure. The inhibition of Pgp at the blood-brain barrier by Boswellia extract is probably not relevant for the brain availability of other Pgp substrates, because of the low plasma levels determined for KBA and AKBA. However the presented data could not exclude the possibility of drug interactions caused by modulation of Pgp by extracts of Boswellia serrata on the gastrointestinal level.
Planta Med. 2006 May;72(6):507-13.
PMID: 16773534 [PubMed - indexed for MEDLINE]
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| 65. |
Analysis of frankincense from various Boswellia species with inhibitory activity on human drug metabolising cytochrome P450 enzymes using liquid chromatography mass spectrometry after automated on-line extraction.
Frank A, Unger M
In our search for herbal remedies with inhibitory activity on cytochrome P450 (CYP) enzymes, we identified extracts of the gum-resin of Boswellia carteri, Boswellia frereana, Boswellia sacra and Boswellia serrata as equally potent, non-selective inhibitors of the major drug metabolising CYP enzymes 1A2/2C8/2C9/2C19/2D6 and 3A4. LC/LC/ESI-MS fingerprint analyses of the boswellic acids 11-keto-beta-boswellic acid, alpha-boswellic acid, beta-boswellic acid and their 3-O-acylated derivatives were used for the authentication of the commercially obtained frankincense samples. Although the boswellic acids could be identified as moderate to potent inhibitors of the applied CYP enzymes, they are not the major CYP inhibitory principle of frankincense.
J Chromatogr A. 2006 Apr;1112(1-2):255-62.
PMID: 16364338 [PubMed - indexed for MEDLINE]
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| 66. |
High-performance liquid chromatographic determination of acetyl-11-keto-alpha-boswellic acid, a novel pentacyclic triterpenoid, in plasma using a fluorinated stationary phase and photodiode array detection: application in pharmacokinetic studies.
Büchele B, Zugmaier W, Genze F, Simmet T
A rapid, sensitive and selective HPLC separation with photodiode array detection was developed for the analysis of the novel pentacyclic triterpenoid acetyl-11-keto-alpha-boswellic acid. Complete baseline separation of acetyl-11-keto-alpha-boswellic acid from the corresponding isomer acetyl-11-keto-beta-boswellic acid was achieved on a fluorinated stationary phase. The standard curve was linear from 0.98 nmol/l to 196 nmol/l acetyl-11-keto-alpha-boswellic acid. The compound was isolated from chick embryonic plasma using extraction on diatomaceous earth with an overall average extraction yield of 82%. This method was applied in a kinetic study on the chick chorioallantoic membrane model (CAM) and showed unequivocal separation between acetyl-11-keto-alpha-boswellic acid and acetyl-11-keto-beta-boswellic acid unachievable so far.
J Chromatogr B Analyt Technol Biomed Life Sci. 2005 Dec;829(1-2):144-8.
PMID: 16266833 [PubMed - indexed for MEDLINE]
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| 67. |
Determination of boswellic acids in brain and plasma by high-performance liquid chromatography/tandem mass spectrometry.
Reising K, Meins J, Bastian B, Eckert G, Mueller WE, Schubert-Zsilavecz M, Abdel-Tawab M
Peritumoral edema, one of the major causes for neurological disorders in brain tumor patients, is mainly treated with steroids, which unfortunately have significant side effects and interfere with the efficacy of chemotherapy. Boswellic acids, the main active ingredients of Boswellia serrata, are antiinflammatory agents, inhibiting 5-lipoxygenase, the key enzyme of leukotriene biosynthesis and one of the pathophysiological mechanisms of peritumoral edema. Based on positive results in clinical trials and animal studies, B. serrata resin dry extract was designated an orphan drug by the European Commission for the treatment of peritumoral edema resulting from brain tumors. Thus boswellic acids may be alternative drugs to corticosteroids. However, the question of the availability of boswellic acids in brain has not been addressed until now. Accordingly, a highly sensitive LC/MS method has been developed for the simultaneous determination of KBA and AKBA, the most potent boswellic acids, in plasma and brain. This method involves matrix-assisted liquid-liquid extraction on Extrelut NT followed by separation on reversed-phase high-performance liquid chromatography and tandem mass spectrometry detection using atmospheric pressure chemical ionization. Excellent linearity was obtained for the entire calibration range from 5 to 1500 ng/mL KBA and AKBA in plasma and 5 to 1000 ng/mL KBA and AKBA in brain. Validation assays of the lower limit of quantification as well as for the intra- and interday precision and accuracy met the international acceptance criteria for bioanalytical method validation. Moreover, the interchangeability of calibration curves generated in pork and rat brain homogenates could be demonstrated. Using the developed analytical method, KBA and AKBA could be detected for the first time in brain up to a concentration of 99 and 95 ng/g of brain, respectively, 3 h after the single oral administration of 240 mg/kg of dry B. serrata resin extract to Wistar rats. The developed method represents an appropriate tool to further study the time-dependent distribution of KBA and AKBA in plasma and brain as well as the absolute brain concentration after multiple doses and contributes thus to the optimization of the dosage regimen and to a better understanding of the therapeutic effects of B. serrata.
Anal Chem. 2005 Oct;77(20):6640-5.
PMID: 16223251 [PubMed - indexed for MEDLINE]
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| 68. |
Effect of food intake on the bioavailability of boswellic acids from a herbal preparation in healthy volunteers.
Sterk V, Büchele B, Simmet T
In this study we investigated the effects of concomitant food intake on the bioavailability of distinct boswellic acids (BAs) from the test preparation BSE-018, a dry extract from Boswellia serrata gum resin. In a randomised, open, single-dose, two-way crossover study, healthy male subjects received three capsules of BSE-018 equivalent to 786 mg dry extract of Boswellia serrata gum resin either in the fasted state or together with a standardised high-fat meal. BA plasma concentrations were analysed for up to 60 h after oral dosing by reversed phase HPLC. As compared to the fasted state (treatment A), the administration of BSE-018 concomitantly with a high-fat meal (treatment B) led to several-fold increased areas under the plasma concentration-time curves as well as peak concentrations of beta-boswellic acid (betaBA), 11-keto-beta-boswellic acid (KbetaBA) and acetyl-11-keto-beta-boswellic acid (AKbetaBA). Plasma levels of both acetyl-alpha-boswellic acid (AalphaBA) and alphaBA became only detectable when administered with treatment B, i.e., the high-fat meal. Accordingly, pharmacokinetic data could be calculated for betaBA, KbetaBA and AKbetaBA (treatment A) and for betaBA, KbetaBA, AKbetaBA, alphaBA, and AalphaBA (treatment B). For the first time these data reveal detailed kinetics of BAs after oral dosing of an extract and demonstrate a profound effect of food intake on the pharmacokinetic profile of the BAs. This finding should be very important whenever BAs would be considered for therapeutic use.
Planta Med. 2004 Dec;70(12):1155-60.
PMID: 15643550 [PubMed - indexed for MEDLINE]
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| 69. |
Pharmacokinetic study of 11-Keto beta-Boswellic acid.
Sharma S, Thawani V, Hingorani L, Shrivastava M, Bhate VR, Khiyani R
INTRODUCTION: Boswellia serrata has been used in traditional medicine for treatment of inflammatory diseases since antiquity. However human kinetic studies are lacking for this. Hence to better elucidate its effects in humans and determine its optimal dosing, this study was planned.
MATERIAL AND METHODS: Twelve healthy adult men volunteers were given capsule Wok Vel containing 333 mg of Boswellia Serrata Extract, orally, after a seven days washout period. Venous blood samples were drawn through indwelling canula from each volunteer prior to drug administration and at 30, 60, 120, 150, 180, 210, 240, 300, 360, 480, 600, 720, 840 minutes after drug administration. Plasma obtained after centrifuge was analyzed to measure concentration of 11-Keto beta-Boswellic Acid (KBA) by HPLC. Various kinetic parameters were then calculated from the plasma concentrations.
RESULTS: The results are expressed as mean +/- Standard Error of Mean. The peak plasma levels (2.72 x 10(-3) +/- 0.18 micromoles/ml) of BSE were reached at 4.5 +/- 0.55 h. The concentration declined with a mean elimination half life of 5.97 +/- 0.95 h. The apparent volume of distribution averaged 142.87 +/- 22.78 L and the plasma clearance was 296.10 +/- 24.09 ml/min. The AUC(0-infinity) was 27.33 x 10(-3) +/- 1.99 micromoles/ml h.
CONCLUSION: Elimination half life of nearly six hours suggests that the drug needs to be given orally at the interval of six hours. The plasma concentration will attain the steady state after approximately 30 hours. BSE is a safe drug and well tolerated on oral administration. No adverse effects were seen with this drug when administered as single dose in 333 mg.
Phytomedicine. 2004 Feb;11(2-3):255-60.
PMID: 15070181 [PubMed - indexed for MEDLINE]
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| 70. |
Analysis of 12 different pentacyclic triterpenic acids from frankincense in human plasma by high-performance liquid chromatography and photodiode array detection.
Büchele B, Simmet T
For the determination of pentacyclic triterpenes of the boswellic acid family in human plasma a novel sensitive method was developed combining serial extraction on diatomaceous earth and graphitized carbon black followed by reversed phase high-performance liquid chromatography (HPLC) and photodiode array detection. The overall average extraction yield of 12 different pentacyclic triterpenic acids was approximately 66%. The calibration graphs were linear with coefficients of correlation for all compounds greater than 0.999. The overall within-day and between-day coefficients of variation (CV) for the 12 pentacyclic triterpenic acids were 5.6 and 6.8%, respectively. This HPLC procedure delivers the analytical sensitivity, precision and accuracy required for clinical pharmacokinetic and therapeutic studies.
J Chromatogr B Analyt Technol Biomed Life Sci. 2003 Oct;795(2):355-62.
PMID: 14522040 [PubMed - indexed for MEDLINE]
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| 71. |
Determination of 11-keto-boswellic acid in human plasma.
Kaunzinger A, Baumeister A, Cuda K, Häring N, Schug B, Blume HH, Raddatz K, Fischer G, Schubert-Zsilavecz M
A sensitive, specific, accurate, fast and reproducible GC/MS-method for the quantitative determination of 11-keto-boswellic acid in human plasma using 18alpha-glycyrrhetinic acid as the internal standard was developed and validated. 11-Keto-boswellic acid and the internal standard were separated from acidified plasma by liquid/liquid extraction. The extracted samples were methylated and analyzed by GC/MS in the negative ion chemical ionization mode (NICI) and selected ion monitoring (SIM). The total run time was 8 min between injections. The assay described in this paper demonstrates a validated lower limit of quantification of 0.0100 microg/ml using 1 ml of plasma. The calibration curves are linear in the measured range between 10.0 and 2000 ng/ml plasma. The overall precision (expressed as CV) and accuracy (expressed as bias) for all concentrations of quality controls and standards is better than 15%. No indications were found for possible instabilities of 11-keto-boswellic acid in plasma, in whole blood, in the extraction solvent or after repeated thawing/freezing cycles. The recovery of the extraction method is calculated as 84%. The assay was applied successfully to determine the plasma level of 11-keto-boswellic acid in a clinical pilot study.
J Pharm Biomed Anal. 2002 May;28(3-4):729-39.
PMID: 12008153 [PubMed - indexed for MEDLINE]
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| 72. |
Development of a high-performance liquid chromatographic method for the determination of 11-keto-beta-boswellic acid in human plasma.
Tawab MA, Kaunzinger A, Bahr U, Karas M, Wurglics M, Schubert-Zsilavecz M
A validated HPLC method for the determination of 11-keto-beta-boswellic acid (KBA) in human plasma was developed. The method involves the solid-phase extraction of KBA from plasma followed by a separation with reversed-phase HPLC. Calibration was based on external standardisation and ranged between 0.1 and 2.0 microg KBA per ml plasma. Linearity was established over the entire calibration range and in each case the coefficient of correlation (r2) was above 0.99. The recovery of KBA from plasma was 85.7%. It was further demonstrated that the method can be applied successfully to monitor the level of KBA in plasma.
J Chromatogr B Biomed Sci Appl. 2001 Sep;761(2):221-7.
PMID: 11587352 [PubMed - indexed for MEDLINE]
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