| 1. |
Single-Center-Single-Blinded Clinical Trial to Evaluate the Efficacy of a Nutraceutical Containing Boswellia Serrata, Bromelain, Zinc, Magnesium, Honey, Tyndallized Lactobacillus Acidophilus and Casei to Fight Upper Respiratory Tract Infection and Otitis Media.
Della Volpe A, De Luca P, De Lucia A, Martines F, Piroli P, D'Ascanio L, Camaioni A, La Mantia I, Di Stadio A
Some nutraceuticals have been studied as supportive treatment for fighting upper respiratory tract infection and middle ear disease. Our study aims at evaluating the effect of a specific oral supplementation in the treatment of pediatric otits media. The subjects were randomly assigned by the physician (single-blinded study) to one of three groups: Control Group (CG), Treatment Group 1 (TG1), or Treatment Group 2 (TG2). Both TG were treated with Flogostop Duo (for 20 days-TG1 or 30 days-TG2) in combination with the standard treatment, while CG underwent standard treatment only. The standard treatment was nasal aerosol with Fluticasone and Mucolytic, and nasal washing with hypertonic solution. All patients were analyzed by otoscopy, impedance, fibroscopy, and pure auditory test at the baseline (T0), after 20 days (T1) and 35 days (T2). 120 children were included in the study, 40 in the CG, 40 in the TG1, and 40 in the TG2. Both TG1 and TG2 presented statistically significant differences with respect to controls in otoscopy, impedance, fibroscopy, and PTA at T2. The otoscopy improved at T2 with statistically significant value only in TG2. The impedance and fibroscopy improved at T1 both in TG1 and TG2 compared to CG. A statistically significant improvement was observed in TG2 at T2 in comparison to both CG and TG1. Statistically significant differences were observed in PTA at T2 only compared with controls. This study confirmed the efficacy of nutraceutical as supporting therapy in the upper respiratory tract infection in children. In particular, the supplement containing Boswellia serrata and Bromelain, which are molecules with strong anti-inflammatory and pain-control capacities, could add the benefit without the adverse effects which are related to NSAID use.
Healthcare (Basel). 2022 Aug;10(8):.
PMID: 36011184 [PubMed - as supplied by publisher]
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| 2. |
Acute and sub chronic toxicity studies with herbal pain relieving formula (Rhuleave-K™) in rats.
Antony B, Benny M, Kuruvilla BT, Gupta NK, Jacob S
Rhuleave-K™ is a proprietary combination of Curcuma longa extract, Boswellia serrata extract and black sesame seed oil. Acute toxicity was evaluated as per OECD guidelines 423. Rhuleave-K™ was fed at 2000 mg/kg to overnight fasted female rats. Clinical signs of abnormality and mortality was observed daily for 14 days. Sub-chronic toxicity was studied by feeding Rhuleave-K™ at 100, 500 and 1000 mg/kg/day to rats as per OECD guidelines 408. After 90 days feeding, hematological and biochemical parameters were analyzed. Histopathology of all the major organs was also studied. In the acute toxicity study, there was no clinical sign of toxicity in any of the rats at maximum dose of 2000 mg/kg. The LD50 was computed as >2000 mg/kg in rats. The repeated dosing of Rhuleave-K™ at the maximum dose level of 1000 mg/kg for 90 days did not induce any observable toxic effects in rats, when compared to its corresponding control. The hematology and biochemistry profiles of treated rats were similar to control animals and difference was non-significant (p > 0.05). The histopathology of major organs of all the control and treated animals was normal. In this study the NOAEL for Rhuleave-K™ was calculated as 1000 mg/kg daily in rats.
Regul Toxicol Pharmacol. 2022 Aug;133():105214.
PMID: 35781033 [PubMed - indexed for MEDLINE]
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| 3. |
Safety and efficacy of a feed additive consisting of an extract of olibanum from Roxb. ex Colebr. for use in dogs and horses (FEFANA asbl).
, Bampidis V, Azimonti G, Bastos ML, Christensen H, Fašmon Durjava M, Kouba M, López-Alonso M, López Puente S, Marcon F, Mayo B, Pechová A, Petkova M, Ramos F, Sanz Y, Edoardo Villa R, Woutersen R, Brantom P, Chesson A, Westendorf J, Manini P, Pizzo F, Dusemund B
Following a request from the European Commission, the EFSA Panel on Additives and Products or Substances used in Animal Feed (FEEDAP) was asked to deliver a scientific opinion on the safety and efficacy of olibanum extract from Roxb. ex Colebr., when used as a sensory additive (flavouring) in feed for all dogs and horses. The FEEDAP Panel concluded that the additive under assessment is safe for horses at the maximum proposed use level of 100 mg/kg in complete feed. For dogs, the calculated safe concentration in feed is 330 mg/kg complete feed. The additive is considered safe for consumers when used at the proposed conditions of use in horses. The additive under assessment should be considered as non-irritant to skin and eyes, but in the absence of data, no conclusion can be drawn on its potential to be a dermal and respiratory sensitiser. The use of the additive under the proposed conditions of use in feed for horses was not expected to pose a risk for the environment. species and their preparations were recognised to flavour food. Since their function in feed would be essentially the same as that in food, no further demonstration of efficacy was considered necessary.
EFSA J. 2022 Mar;20(3):e07158.
PMID: 35281639 [PubMed - as supplied by publisher]
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| 4. |
Safety assessment of a novel water-soluble extract of gum resin: acute toxicity, 90-day sub-chronic toxicity, Ames' bacterial reverse mutation, and micronucleus assays.
Dodda S, Madireddy RK, Alluri VK, Golakoti T, Sengupta K
gum resin extracts have demonstrated potential benefits in alleviating joint pain and discomfort of osteoarthritis. The major objective of the present study was to assess the safety of a water-soluble gum resin extract (LI51202F1) in diverse models of acute oral, acute dermal, primary dermal irritation, eye irritation, and 90-day sub-chronic repeated dose toxicity studies, as well as Ames' bacterial reverse mutation assay and micronucleus assay. The acute oral and dermal toxicity studies in (SD) rats demonstrated that the median lethal dose (LD) of LI51202F1 is >2000 mg/kg body weight (BW). The acute dermal and eye irritation tests in New Zealand white rabbits exhibited that LI51202F1 is non-irritating to the skin and mildly irritating to the eyes, respectively. The 90-days sub-chronic repeated oral dose study demonstrated that the LI51202F1-treated male and female SD rats did not show signs of toxicity on their BW, food intake, organ weights, thyroid hormones, and on the clinical pathology, gross pathology, and histopathological assessments. In male and female rats, the no-observed-adverse-effect level (NOAEL) of LI51202F1 was 500 mg/kg/day, the highest tested dose in the study. The results of the bacterial reverse mutation assay in TA98, TA100, TA1535, TA1537, and WP2uvrA (pKM101) strains in the presence or absence of S9 metabolic activation system and a micro-nucleus assay in mouse bone marrow erythrocytes demonstrated that LI51202F1 is neither mutagenic nor clastogenic. In conclusion, under the conditions of these studies, LI51202F1 demonstrated broad-spectrum safety.
Toxicol Mech Methods. 2022 Jun;32(5):362-372.
PMID: 34886755 [PubMed - indexed for MEDLINE]
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| 5. |
Allergic contact dermatitis from Boswellia carterii (frankincense) oil.
Buonomo M, Hylwa S
Contact Dermatitis. 2021 Oct;85(4):465-467.
PMID: 33963563 [PubMed - indexed for MEDLINE]
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| 6. |
Haematotoxic effects of methanolic extract of oleo gum resin (frankinccense) in rats.
Alyahya AAI, Asad M, Asdaq SMB, Mohzari Y, Alrashed A, Alajami HN, Aljohani AO, Al Mushtawi AA, Alajmi A, Alajmi HN
In several parts of the world, Fluck. is one of the most commonly used herbs for the treatment of arthritis. Its usage should be validated in light of recent findings of haematotoxicity. This study was aimed to determine the effect of chronic administration of standardized methanolic extract of frankincense on blood cell count in experimental animals. Using high-performance liquid chromatography, the active constituents of extract; boswellic acids were analyzed. The effect of three different doses of the extract (250, 500, and 1000 mg/kg) on different blood cells and associated parameters was investigated. The behavior, food, and water consumption of the rats were recorded. Boswellic acids were present in varying amounts with α-boswellic acid and β-boswellic acid present in more amounts compared to other boswellic acids in the extract. All three doses tested had no effect on the animals' behavior, food consumption, or weight gain. The administration of a low (500 mg/kg) and high (1000 mg/kg) dose of the extract resulted in a non-dose dependent reduction in MCH ( < 0.01 and < 0.05, respectively), but no other blood parameters were significantly affected. The extract produces hypochromic normocytic anemia in rats at higher doses of 500 and 1000 mg/kg and this effect was not dose-dependent.
Sci Prog. 2021;104(2):368504211015102.
PMID: 33949902 [PubMed - indexed for MEDLINE]
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| 7. |
Repeated 28-DAY oral dose study on Boswellia sacra oleo gum resin extract for testicular toxicity in rats.
Alyahya AAI, Asad M
ETHNOPHARMACOLOGICAL RELEVANCE: Frankincense (Boswellia sacra Fluck.,) is a widely used herbal drug and household medicine for treatment of several diseases. Earlier toxicological studies revealed its proulcerogenic effect and no significant hepatotoxic or nephrotoxic effects in rats. However, some other members of Boswellia species such as Boswellia papyrifera (Caill. ex Delile) Hochst and Boswellia carterii have been reported for testicular toxicity in rats.
AIM OF THE STUDY: Testicular toxicity of standardized methanolic extract of B. sacra oleo gum resin was determined through repeated oral dose administration for 28 days. Biochemical, histological and genetic changes in rat testes were evaluated.
MATERIALS AND METHODS: B. sacra extract was analyzed for its boswellic acid content by high performance liquid chromatography (HPLC) method. The extract was administered at three different doses to rats. Effect on behavior, weight, food and water consumption along with changes in serum testosterone levels and cytoarchitecture of testis, epididymis and adrenal gland were determined. Gene expression of GSTPi, IGFBP3 and HSP70 in testis was also studied.
RESULTS: Boswellic acids (α and β) were present in highest concentration whereas acetyl-11-keto beta boswellic acid was present in relatively smaller amounts. The extract did not produce any significant change in the behavior of the animals, food/water consumption or weight gain. Serum testosterone levels were significantly decreased only by highest tested dose of Boswellia extract (1000 mg/kg, p.o). Histological examination did not reveal any variation in the structure of testis, adrenal gland and epididymis after administration of the extract while the expression of all three studied genes was significantly decreased.
CONCLUSION: The results indicate that B. sacra extract does not possess any toxic effect on testis. On the contrary, decrease in gene expression of GSTPi, IGFBP3 and HSP70 revealed its antioxidant potential that may protect testes against effect of toxicants. However, a significant reduction in serum testosterone levels point to mechanisms other than direct testicular toxicity.
J Ethnopharmacol. 2020 Aug;258():112890.
PMID: 32330512 [PubMed - indexed for MEDLINE]
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| 8. |
11-Keto-β-Boswellic Acid Attenuates Glutamate Release and Kainic Acid-Induced Excitotoxicity in the Rat Hippocampus.
Lu CW, Lin TY, Wang SJ
Excessive glutamate concentration induces neuronal death in acute brain injuries and chronic neurodegenerative diseases. Natural compounds from medicinal plants have attracted considerable attention for their use in the prevention and treatment of neurological disorders. 11-Keto--boswellic acid, a triterpenoid found in the medicinal plant , has neuroprotective potential. The present study investigated the effect of 11-keto--boswellic acid on glutamate release and kainic acid-induced glutamate excitotoxicity in the rat hippocampus. In rat hippocampal nerve terminals (synaptosomes), 11-keto--boswellic acid dose-dependently inhibited 4-aminopyridine-stimulated glutamate release. This effect was dependent on extracellular calcium, persisted in the presence of the glutamate transporter inhibitor DL-threo--benzyloxyaspartate, and was blocked by the vesicular transporter inhibitor bafilomycin A1. In addition, 11-keto--boswellic acid reduced the 4-aminopyridine-induced increase in intrasynaptosomal Ca levels. The N- and P/Q-type channel blocker -conotoxin MVIIC and the protein kinase A inhibitor H89 significantly suppressed the 11-keto--boswellic acid-mediated inhibition of glutamate release, whereas the intracellular Ca-releasing inhibitors dantrolene, CGP37157, and xestospongin C, mitogen-activated protein kinase inhibitor PD98059, as well as protein kinase C inhibitor calphostin C had no effect. In a rat model of excitotoxicity induced by intraperitoneal kainic acid injection (15 mg/kg), intraperitoneal 11-keto--boswellic acid administration (10 or 50 mg/kg) 30 min before kainic acid injection considerably ameliorated kainic acid-induced glutamate concentration elevation and CA3 neuronal death. These data suggested that 11-keto--boswellic acid inhibits glutamate release from the rat hippocampal synaptosomes by suppressing N- and P/Q-type Ca channels and protein kinase A activity, as well as exerts protective effects against kainic acid-induced excitotoxicity .
Planta Med. 2020 Apr;86(6):434-441.
PMID: 32097973 [PubMed - indexed for MEDLINE]
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| 9. |
Repeat oral dose safety study of standardized methanolic extract of Boswellia sacra oleo gum resin in rats.
Al-Yahya AAI, Asad M, Sadaby A, Alhussaini MS
The oleo gum resin of Fleuck. (Burseraceae) is widely consumed for treatment of several diseases and disorders. To determine the effect of repeated administration of this resin on liver and kidney functions, three different doses of standardized methanolic extract were administered orally to rats for 28 days. Apart from histological studies and determination of biomarkers of hepatotoxicity and nephrotoxicity, other parameters of sub-chronic toxicity such as behavioral change, food consumption and change in body weight were assessed. The extract contained about 36.91% of total boswellic acids; of which 11-keto beta boswellic acid, acetyl-11-keto beta boswellic acid, boswellic acids (α and β) and acetyl boswellic acid (α and β) were found to be 5.81%, 1.91%, 21.92% and 7.27% respectively. Oral administration of the extract for 28 consecutive days did not show any sign of behavioral toxicity and did not affect food consumption or weight gain significantly. Determination of biomarkers of hepatic and nephrotoxicity revealed that extract was safe at the tested doses as it did not produce any significant change in the studied biomarkers except producing a dose dependent increase in serum total protein levels. The histological examination supported biochemical findings. To conclude, methanolic extract of doen not produce any significant toxicity to liver and kidney up to doses of 100 mg/kg body weight. The results contradict earlier reports that members of species produce organ toxicity in rats.
Saudi J Biol Sci. 2020 Jan;27(1):117-123.
PMID: 31889825 [PubMed - as supplied by publisher]
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| 10. |
Induction of developmental toxicity and cardiotoxicity in zebrafish embryos/larvae by acetyl-11-keto-β-boswellic acid (AKBA) through oxidative stress.
Han L, Xia Q, Zhang L, Zhang X, Li X, Zhang S, Wang L, Liu C, Liu K
Acetyl-11-keto-β-boswellic acid (AKBA), a triterpenoid from , is regarded as an angiogenesis inhibitor. However, its toxicity is unknown. The aim of this study was to examine its developmental toxicity and cardiotoxicity. A developmental toxicity assay in zebrafish embryos/larvae from 4 to 96 hours post-fertilization (hpf) was performed and a cardiotoxicity assay was designed from 48 to 72 hpf. Markers of oxidative stress and related genes were selected to access the possible mechanisms. According to the results, AKBA induced pericardium edema, yolk-sac edema, abnormal melanin, spinal curvature, hatching inhibition and shortened body length. Further, increased SV-BA distance, reduced heart rate, increased pericardium area and decreased blood flow velocity were detected in AKBA treated groups. The inhibition of cardiac progenitor gene expression, such as and , may be related to cardiotoxicity. The activities of antioxidant enzymes were decreased and the content of MDA was increased. In addition, AKBA treatment decreased the expression levels of , , and . These results suggested that AKBA induced developmental toxicity and cardiotoxicity through oxidative stress. As far as we know, this is the first report on the toxicity of AKBA. It reminds us to pay attention to developmental toxicity and cardiotoxicity of AKBA.
Drug Chem Toxicol. 2022 Jan;45(1):143-150.
PMID: 31656113 [PubMed - indexed for MEDLINE]
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| 11. |
Toxicological studies and bioactivity-guided identification of antimicrobially active compounds from crude aqueous stem bark extract of .
Dandashire BS, Magashi AM, Abdulkadir B, Abbas MA, Goni MD, Yakubu A
OBJECTIVE: The main objective of this study is to isolate, identify, and quantify the active antimicrobial compounds present in the crude aqueous stem bark extract of using some common pathogenic microorganisms as well as toxicological profile.
MATERIAL AND METHODS: Crude aqueous stem bark extract of (CASEB) was partitioned by preparative thin layer chromatography (PTLC) using chloroform-methanol-water, 8:2:1 (v/v). The resulting bands were extracted using chloroform-methanol (50:50). The extract of each band was evaluated for antimicrobial activity on , , , , , , , , and by disc diffusion. Compounds in the most antimicrobially bioactive fraction (MAAF) were identified by high performance liquid chromatography (HPLC), Fourier transform infrared spectrophotometry (FT-IR), and gas chromatography-mass spectrometry (GC-MS). Toxicological profile of the CASEB was evaluated by studying its effect in albino Wister rats.
RESULTS: PTLC produced five bands/fractions of which the MAAF was identified as RF-fraction being active against all the isolates except and HPLC of the MAAF revealed seven components; FT-IR revealed 17 functional groups; GC-MS revealed five compounds of which 93.18% are Oleic acid (44.88%), Squalene (34.16%), and n-Hexadecanoic acid (14.14%). The acute toxicity showed LD > 3,000 mg/kg. Sub-chronic toxicity showed that higher doses of the CASEB caused significant changes in liver function indices and a fatty change with lymphocytic infiltration (sign of acute hepatitis) in the liver tissues, but none of these changes were observed in the kidneys.
CONCLUSION: The antimicrobially active compounds in CASEB were Oleic acid, Squalene, and n-Hexadecanoic acid. These can be further purified and used as precursors of new antimicrobial agents for treating infections especially those due to fungi and spp. that are known to resist wide array of antimicrobial agents. The LD of CASEB is >3,000 mg/kg in rats. However, long-term consumption of CASEB is associated with significant liver damage.
J Adv Vet Anim Res. 2019 Jun;6(2):183-192.
PMID: 31453189 [PubMed - as supplied by publisher]
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| 12. |
Toxicological Assessment of a Standardized Gum Resin Extract.
Alluri VK, Dodda S, Kilari EK, Golakoti T, Sengupta K
The acidic and non-acidic fractions of gum resin extracts were combined to prepare a unique product, LI13019F1 (Serratrin). The present series of studies evaluated LI13019F1 for acute and subchronic (28-day) toxicity in Wistar rats and acute dermal and eye irritation in New Zealand white rabbits. The mutagenicity and clastogenicity of LI13019F1 were evaluated in bacteria and mouse bone marrow erythrocytes, respectively. All studies were performed following the Organization for Economic Co-operation and Development guidelines. Acute oral and acute dermal toxicity studies did not show mortality or signs of toxicity in Wistar rats at a limit dose of 2,000 mg/kg LI13019F1. LI13019F1 did not cause irritation to the skin or the eyes of New Zealand white rabbits. In a repeated dose 28-day oral toxicity study, LI13019F1-treated Wistar rats did not show dose-related signs of toxicity on their body weights, organ weights, and on the hematology and clinical chemistry parameters. The estimated no observed adverse effect level for LI13019F1 was 1,000 mg/kg/day in both male and female rats. The bacterial reverse mutation test and a micronucleus assay in mouse bone marrow erythrocytes revealed that LI13019F1 was neither mutagenic nor clastogenic. Together, the present observations demonstrate a broad-spectrum safety of LI13019F1.
Int J Toxicol. 2019;38(5):423-435.
PMID: 31234670 [PubMed - indexed for MEDLINE]
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| 13. |
Assessment of toxicity and biochemical mechanisms underlying the insecticidal activity of chemically characterized Boswellia carterii essential oil against insect pest of legume seeds.
S K, Kujur A, Patel L, K R, Prakash B
The present study was undertaken to investigate the insecticidal activity of chemically characterized Boswellia carterii essential oil (EO) and its mode of action against the pulse beetle Callosobruchus chinensis and C. maculatus. GC-MS analysis depicted α-thujene (69.16%), α-Pinene (7.20) and α-Phellandrene (6.78%) as the major components of test EO. EO exhibited absolute toxicity at 0.10μl/ml air against both C. chinensis and C. maculatus following 24h exposure. EO caused a significant reduction in oviposition and further reproductive development at LC doses (0.050μl/ml to 0.066μl/ml in air). Compared to control, a significant elevation in ROS level accompanied with impairment in enzymatic (SOD and CAT) and non-enzymatic (GSH/GSSH) antioxidant defense system has been observed in EO exposed insect pest. However, EO has no significant effect on in vivo AChE activity. An absolute protection of Vigna radiata seeds samples exposed to EO at LC doses was observed without affecting seed germination. The findings revealed that the B. carterii EO has strong insecticidal potential, hence, it could be recommended as a biorational alternative to synthetic insecticides.
Pestic Biochem Physiol. 2017 Jun;139():17-23.
PMID: 28595917 [PubMed - indexed for MEDLINE]
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| 14. |
Defined Structure-Activity Relationships of Boswellic Acids Determine Modulation of Ca2+ Mobilization and Aggregation of Human Platelets by Boswellia serrata Extracts.
Siemoneit U, Tausch L, Poeckel D, Paul M, Northoff H, Koeberle A, Jauch J, Werz O
Boswellic acids constitute a group of unique pentacyclic triterpene acids from with multiple pharmacological activities that confer them anti-inflammatory and anti-tumoral properties. A subgroup of boswellic acids, characterized by an 11-keto group, elevates intracellular Ca concentrations [Ca] and causes moderate aggregation of human platelets. How different BAs and their mixtures in pharmacological preparations affect these parameters in activated platelets has not been addressed, so far. Here, we show that boswellic acids either antagonize or induce Ca mobilization and platelet aggregation depending on defined structural determinants with inductive effects predominating for a gum resin extract. 3--Acetyl-11-keto--boswellic acid potently suppressed Ca mobilization (IC = 6 µM) and aggregation (IC = 1 µM) when platelets were activated by collagen or the thromboxane A receptor agonist U-46619, but not upon thrombin. In contrast, -boswellic acid and 3--acetyl--boswellic acid, which lack the 11-keto moiety, were weak inhibitors of agonist-induced platelet responses, but instead they elicited elevation of [Ca] and aggregation of platelets (≥ 3 µM). 11-Keto--boswellic acid, the structural intermediate between 3--acetyl-11-keto--boswellic acid and -boswellic acid, was essentially inactive independent of the experimental conditions. Together, our study unravels the complex agonizing and antagonizing properties of boswellic acids on human platelets in pharmacologically relevant preparations of gum extracts and prompts for careful evaluation of the safety of such extracts as herbal medicine in cardiovascular risk patients.
Planta Med. 2017 Aug;83(12-13):1020-1027.
PMID: 28403501 [PubMed - indexed for MEDLINE]
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| 15. |
Pharmacokinetic and Pharmacodynamic Interaction of Boswellic Acids and Andrographolide with Glyburide in Diabetic Rats: Including Its PK/PD Modeling.
Samala S, Veeresham C
The effect of boswellic acids (BA) and andrographolide (AD) on the pharmacokinetics and pharmacodynamics of glyburide in normal as well as in streptozotocin-induced diabetic rats was studied. In normal and diabetic rats, the combination of glyburide with BA or AD increased significantly (p < 0.01) all the pharmacokinetic parameters, such as Cmax, AUC0-n, AUCtotal, t1/2, and mean residence time, and decreased the clearance, Vd, markedly as compared with the control group. In rat liver, microsomes BA and AD have shown CYP3A4 inhibitory activity significantly (p < 0.01), compared with the vehicle group. The increase in hypoglycemic action by concomitant administration of glyburide with BA or AD was more in diabetic rats than when the drugs were used singly and with the control group, which suggests the enhancement of glucose reduction capacity of glyburide in diabetic rats along with BA or AD. In PK/PD modeling of BA and AD with glyburide, the predicted PK and PD parameters are in line with the observed PK and PD parameters. The results revealed that BA and AD led to the PK/PD changes because of glyburide-increased bioavailability and because of the inhibition of CYP3A4 enzyme. In conclusion, add-on preparations containing BA or AD may increase the bioavailability of glyburide, and hence the dose should be monitored.
Phytother Res. 2016 Mar;30(3):496-502.
PMID: 26762235 [PubMed - indexed for MEDLINE]
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| 16. |
Triggering of Suicidal Erythrocyte Death Following Boswellic Acid Exposure.
Calabrò S, Alzoubi K, Faggio C, Laufer S, Lang F
BACKGROUND/AIMS: The antinflammatory natural product boswellic acid is effective against cancer at least in part by inducing tumor cell apoptosis. Similar to apoptosis of nucleated cells erythrocytes may enter eryptosis, a suicidal death characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Stimulators of eryptosis include oxidative stress, increase of cytosolic Ca(2+)-activity ([Ca(2+)]i), energy depletion, ceramide formation and p38 kinase activation. The present study tested, whether and how boswellic acid induces eryptosis.
METHODS: Phosphatidylserine exposure at the cell surface was estimated from annexin V binding, cell volume from forward scatter, hemolysis from hemoglobin release, [Ca(2+)]i from Fluo3-fluorescence, ceramide abundance utilizing specific antibodies, reactive oxygen species (ROS) from 2',7'-dichlorodihydrofuorescein diacetate (DCFDA) fluorescence, and cytosolic ATP concentration utilizing a luciferin-luciferase assay kit.
RESULTS: A 24 hours exposure of human erythrocytes to boswellic acid (5 µg/ml) significantly increased the percentage of annexin-V-binding cells (to 9.3 ± 0.9 %) and significantly decreased forward scatter. Boswellic acid did not significantly modify [Ca(2+)]i, cytosolic ATP, ROS, or ceramide abundance. The effect of boswellic acid on annexin-V-binding was significantly blunted, but not abolished by p38 kinase inhibitors skepinone (2 µM) and SB203580 (2 µM).
CONCLUSIONS: Boswellic acid stimulates cell shrinkage and phospholipid scrambling of the erythrocyte cell membrane, an effect in part dependent on p38 protein kinase activity.
Cell Physiol Biochem. 2015;37(1):131-42.
PMID: 26303375 [PubMed - indexed for MEDLINE]
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| 17. |
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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| 18. |
Proulcerogenic effect of water extract of Boswellia sacra oleo gum resin in rats.
Asad M, Alhomoud M
CONTEXT: The water extract of Boswellia sacra Flueck. (Burseraceae) is used in the treatment of gastric and hepatic disorders in the Arab countries.
OBJECTIVE: The effect of Boswellia sacra water extract on gastric secretion and experimentally induced gastric ulcers in rats was studied.
MATERIALS AND METHODS: Acetic acid-induced chronic gastric ulcers, pylorus ligation, aspirin-induced, ethanol-induced, and restraint plus cold stress-induced gastric ulcer models were employed. The effect on normal rats was also studied. The water extract of B. sacra was administered orally at doses of 2 and 5 ml/kg once daily ranging from single dose to 30 d treatment depending on the model. The extract was subjected to GC-MS analysis to determine the presence of various phytoconstituents.
RESULTS: Boswellia sacra water extract (5 ml/kg, p.o (per os)) aggravated acetic acid-induced chronic ulcers, wherein an increase in ulcer index (p < 0.01) and ulcer score (p < 0.05) was observed. In pylorus-ligated rats, the extract increased gastric content volume (p < 0.01), free acidity (p < 0.01), total acidity (p < 0.01), ulcer index (p < 0.01), and pepsin activity (p < 0.05). There was no significant effect on the development of ethanol-induced and aspirin-induced ulcers while an increase in the development of stress-induced ulcers was observed (p < 0.01). The extract did not produce any ulcers when administered to normal rats. The dose of 2 ml/kg was less proulcerogenic compared with 5 ml/kg. The GC-MS analysis revealed the presence of several phytoconstituents that included menthol, 3-cyclohexen-1-ol, and octanoic acid.
CONCLUSION: Boswellia sacra water extract has proulcerogenic activity due to its gastric hypersecretory effect.
Pharm Biol. 2016;54(2):225-30.
PMID: 25853959 [PubMed - indexed for MEDLINE]
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| 19. |
Warfarin interactions with medicinal herbs.
Milić N, Milosević N, Golocorbin Kon S, Bozić T, Abenavoli L, Borrelli F
Recognition of the adverse effects of medicinal herbs is not routine and the reports on such effects are even less frequent in clinical practice. Potential herb-drug interactions are of a major safety concern, especially for drugs with narrow therapeutic indices like warfarin, which can lead to severe adverse reactions that are sometimes life-threatening. The interactions between warfarin and medicinal herbs described in the literature have been summarized in this paper relying on Medline database (via PubMed) using the key words: warfarin, herbal supplements and interactions. The references on the analyzed literature have been investigated in order to collect the existing data. The case reports with severe adverse effects such as spontaneous postoperative bleeding, formation of hematomas, hematemesis, melena, thrombosis, subarachnoid hemorrhage and/or subdural hematomas after concomitant use of warfarin and the medicinal herbs: Panax ginseng, Hypericum perforatum, Salvia milthiorizza, Gingko biloba, Serenoa repens, Angelica sinensis, Vaccinium species, Allium sativum, Zingiber officinale, Tanacetum parthenium, Lucium barbarum, Matricaria chamomilla, Boswellia serrata and Camellia sinensis have been estimated. Some of the interactions between warfarin and medicinal herbs have been well assessed proving that they are closely-dependent. The interactions between warfarin and medicinal herbs, not generally reported in previous reviews, are presented in our review. The health professionals who are involved in treating the patients are expected to be fully informed about the interactions between warfarin and medicinal herbs in order to minimize the health risks of the patients.
Nat Prod Commun. 2014 Aug;9(8):1211-6.
PMID: 25233607 [PubMed - indexed for MEDLINE]
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| 20. |
Holy Saturday asthma.
O'Connor TM, Cusack R, Landers S, Bredin CP
A 61-year-old man complained of cough and dyspnoea after exposure to colophony-containing solder fumes at work. A histamine challenge test confirmed airway hyper-responsiveness, and colophony-challenge demonstrated a 16.7% drop in peak expiratory flow rate (PEFR), supporting a diagnosis of colophony-induced occupational asthma. At review, the patient presented with cough, dyspnoea and wheeze that occurred acutely when exposed to the fumes from burning incense during Easter Saturday services, necessitating his departure from the church. Inhalation challenge tests using two blends of incense used at his church (Greek and Vatican) led to identical symptoms and a significant reduction in forced expiratory volume in 1 s 15 min after exposure and PEFRs up to 48 h after exposure, indicating an early and late phase asthmatic reaction. This is the first report of coexistent colophony and incense-induced asthma. The similarities in chemical structures between abietic acid in colophony and boswellic acid in incense suggest a common mechanism.
BMJ Case Rep. 2014 Mar;2014():.
PMID: 24626388 [PubMed - indexed for MEDLINE]
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| 21. |
Adverse effects of herbal medicines: an overview of systematic reviews.
Posadzki P, Watson LK, Ernst E
This overview of systematic reviews (SRs) aims to evaluate critically the evidence regarding the adverse effects of herbal medicines (HMs). Five electronic databases were searched to identify all relevant SRs, with 50 SRs of 50 different HMs meeting our inclusion criteria. Most had only minor weaknesses in methods. Serious adverse effects were noted only for four HMs: Herbae pulvis standardisatus, Larrea tridentate, Piper methysticum and Cassia senna. The most severe adverse effects were liver or kidney damage, colon perforation, carcinoma, coma and death. Moderately severe adverse effects were noted for 15 HMs: Pelargonium sidoides, Perna canaliculus, Aloe vera, Mentha piperita, Medicago sativa, Cimicifuga racemosa, Caulophyllum thalictroides, Serenoa repens, Taraxacum officinale, Camellia sinensis, Commifora mukul, Hoodia gordonii, Viscum album, Trifolium pratense and Stevia rebaudiana. Minor adverse effects were noted for 31 HMs: Thymus vulgaris, Lavandula angustifolia Miller, Boswellia serrata, Calendula officinalis, Harpagophytum procumbens, Panax ginseng, Vitex agnus-castus, Crataegus spp., Cinnamomum spp., Petasites hybridus, Agave americana, Hypericum perforatum, Echinacea spp., Silybum marianum, Capsicum spp., Genus phyllanthus, Ginkgo biloba, Valeriana officinalis, Hippocastanaceae, Melissa officinalis, Trigonella foenum-graecum, Lagerstroemia speciosa, Cnicus benedictus, Salvia hispanica, Vaccinium myrtillus, Mentha spicata, Rosmarinus officinalis, Crocus sativus, Gymnema sylvestre, Morinda citrifolia and Curcuma longa. Most of the HMs evaluated in SRs were associated with only moderately severe or minor adverse effects.
Clin Med (Lond). 2013 Feb;13(1):7-12.
PMID: 23472485 [PubMed - indexed for MEDLINE]
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| 22. |
A-90 Day Gavage Safety Assessment of Boswellia serrata in Rats.
Singh P, Chacko KM, Aggarwal ML, Bhat B, Khandal RK, Sultana S, Kuruvilla BT
The present study deals with the evaluation and assessment of the safety/toxic potential of Boswellia serrata, a well known Ayurvedic herb used to treat disorders of digestive system, respiratory ailments and bone related diseases. A repeated dose oral (90 days) toxicity study of Boswellia serrata was carried out. For this, 10 rats of each sex were treated with the Boswellia serrata at three different doses i.e. 100, 500 and 1000 mg/kg B. wt. /day. As a control, 10 rats of each sex were treated with corn oil only which was the vehicle. Two groups consisting of five male and five female rats were kept as control recovery and high dose recovery group which were treated with the vehicle (corn oil) and the Boswellia serrata at the dose of 1000 mg/kg B. wt. Animals of control recovery and high dose recovery groups were further observed for 28 days without any treatment. From this study, it was found that the rats treated with high dose of the Boswellia serrata gained their body weight with much less rate than that of the control group. However, during the recovery period, the loss in body weight gain as observed during the study period exhibits a reversible effect on the metabolic activity and recovered. The results also indicate that Boswellia serrata is relatively safe in rat up to the dose of 500 mg/kg B.wt. as no adverse impact on health factors was observed. Thus, the No observed adverse effect level is 500 mg/kg B. wt.
Toxicol Int. 2012 Sep;19(3):273-8.
PMID: 23293466 [PubMed - as supplied by publisher]
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| 23. |
Safety Evaluation of Alcoholic Extract of Boswellia ovalifoliolata Stem-bark in Rats.
Devi PR, Adilaxmamma K, Rao GS, Srilatha Ch, Raj MA
The safety profile of alcoholic extract of stem-bark of B. ovalifoliolata was investigated in male Wistar albino rats as per OECD guidelines 407. A total of 24 male Wistar rats were divided into four groups of six rats each. Group 1 served as control and was given 0.3% carboxymethylcellulose, groups 2, 3 and 4 were given alcoholic extract of B. ovalifoliolata @ 100, 500 and 1000 mg/kg respectively in 0.3% carboxymethylcellulose orally for 28 days. The animals were observed daily for clinical signs, mortality, physiological and behavioral changes. Body weights were measured at weekly intervals and various hematological parameters like Hb, PCV, TEC, TLC and serum biochemical profile which included AST, ALT, creatine phosphokinase, creatinine, total protein and antioxidant parameters like TBARS and GSH in liver were estimated at the end of experimental period. There were no clinical signs of abnormality. The weekly body weights, organ weights and hematological parameters did not vary significantly amongst the groups. The mean activity of AST, ALT and CPK, and the concentration of serum creatinine, total protein, TBARS and GSH did not differ significantly among the groups. Histological abnormalities of toxicological significance were not detected in groups 2 and 3. However, mild histopathological alterations were observed in higher dose group 4. In conclusion, the present study revealed that the alcoholic extract of stem-bark of B. ovalifoliolata is safe at lower doses of 100 and 500 mg/kg. Hence, alcoholic extract of stem bark of B. ovalifoliolata is safe and no observed adverse effect level (NOAEL) is found to be 500 mg/kg following repeated oral administration for 28 days in rats.
Toxicol Int. 2012 May;19(2):115-20.
PMID: 22778507 [PubMed - as supplied by publisher]
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| 24. |
Safety and toxicological evaluation of Aflapin: a novel Boswellia-derived anti-inflammatory product.
Krishnaraju AV, Sundararaju D, Vamsikrishna U, Suryachandra R, Machiraju G, Sengupta K, Trimurtulu G
Boswellia serrata gum resin has been used for treatment of various ailments in different cultures for thousands of years. Aflapin(®) is a novel synergistic composition derived from B. serrata gum resin (Indian Patent Application No. 2229/CHE/2008). Aflapin is significantly better as an anti-inflammatory agent compared to the Boswellia extracts presently available in the market. To assess the safety of Aflapin, a battery of acute and sub-acute toxicity studies were conducted in various animal models according to the OECD test guidelines. The acute oral LD50 of Aflapin was greater than 5000 mg/kg in female Sprague Dawley (SD) rats. Acute dermal LD50 of Aflapin was greater than 2000 mg/kg in SD rats. A primary dermal irritation study conducted using New Zealand White rabbits indicated that Aflapin is non-irritating to skin. Aflapin caused minimal ocular irritation in a primary eye irritation test conducted on New Zealand Albino rabbits. A repeat dose 28-day sub-acute oral toxicity study in SD rats demonstrated no significant signs of toxicity. Various evaluations including hematology, clinical chemistry, gross necropsy, and histopathology did not show any significant adverse changes. The NOAEL of Aflapin was found to be greater than 2500 mg/kg body weight. These studies demonstrate broad spectrum safety of Aflapin in animal models.
Toxicol Mech Methods. 2010 Nov;20(9):556-63.
PMID: 20874664 [PubMed - indexed for MEDLINE]
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| 25. |
Mutagenicity evaluation with Ames test of hydro-alcoholic solution of terpenes.
Lupi S, Marconi S, Paiaro E, Fochesato A, Gregorio P
Mutagenic properties of terpenes (both synthesis and plant derived) have been tested, up to now, as a single molecule. A terpenes containing hydro-alcoholic solution deriving from frankincense and myrrh resins and hyssop essential oil was assayed for mutagenicity by means of ames test. Extraction technique conducted with electromagnetic fields at room temperature enabled to obtain a solution of free active molecules that did not undergo thermal degradation and characterized by biocidal activity. In order to verify lack of mutagenic hazard in coming into contact with human, the solution was appropriately diluted and tested with Salmonella typhimurium TA98, TA1535 and YG1024 strains, both in absence and in presence of metabolic system S9. For none of the tested conditions a 2-fold increase of induced revertants, as regards to spontaneous, was registered. The ratio between induced and spontaneous His+ revertants (Mutagenic Index) was around 1.00 in all the determinations and no statistically significant differences have been identified comparing the sample and the negative control. A similar result has been obtained for the dose-response curve. In conclusion, we verified that tested terpenes solution lacks of mutagenicity on Salmonella typhimurium with and without metabolic activator so this plant extract can be safely used as biocide.
J Prev Med Hyg. 2009 Sep;50(3):170-4.
PMID: 20411651 [PubMed - indexed for MEDLINE]
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| 26. |
In vivo genotoxicity evaluation of a plant based antiarthritic and anticancer therapeutic agent Boswelic acids in rodents.
Sharma R, Singh S, Singh GD, Khajuria A, Sidiq T, Singh SK, Chashoo G, Pagoch SS, Kaul A, Saxena AK, Johri RK, Taneja SC
The genotoxic potential of anti-inflammatory/anti-arthritic and anticancer plant based drug molecule Boswelic acids (BA) was studied by in vivo system. Systematic literature survey revealed that studies on the genotoxicity of BA are not available. Although reports on genotoxicity of Boswellia serrata dry extract and modified 3-O-acetyl-11-keto-beta-boswelic acid are available and these studies were conducted in in vitro systems. The earlier general toxicity study of BA has been conducted by us, revealed it to be non toxic. The genotoxicity was carried out in Wistar rats using different cytogenetic assay system-abnormalities viz. chromosomal aberrations; sperm morphology, micronuclei and comet assays. Six groups of animals, each comprised of five rats, were taken for each study. Group1-4 received BA at 125, 250, 500 and 1000 mg/kg p.o., respectively prepared as 2% gum acacia suspension, fifth group received a positive control cyclophosphamide (CP) 40 mg/kg p.o. or metronedazole (MTZ) 130 mg/kg p.o. or mercuric chloride (HgCl(2)) 0.864 mg/kg p.o. (as per the experiment requirement) whereas the sixth group kept as vehicle control. The results on the bases of the data obtained revealed that BA is quite safe as it did not show any genotoxicity at any dose level up to 1000 mg/kg. The positive controls used in different experiments showed highly significant abnormal cytogenetic changes in comparison to the control group.
Phytomedicine. 2009 Dec;16(12):1112-8.
PMID: 19679457 [PubMed - indexed for MEDLINE]
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| 27. |
Safety and Toxicological Evaluation of a Novel, Standardized 3-O-Acetyl-11-keto-beta-Boswellic Acid (AKBA)-Enriched Boswellia serrata Extract (5-Loxin(R)).
Lalithakumari K, Krishnaraju AV, Sengupta K, Subbaraju GV, Chatterjee A
The novel anti-inflammatory properties of the gum resin derived from Boswellia serrata, also known as Salai guggal in Ayurvedic medicine, are well recognized and highly recommended for human consumption. The active constituents of the gum resin are boswellic acids (BAs). Among the BAs, AKBA potently inhibits 5-lipoxygenase product formation with an IC(50) of 1.5 m muM. We developed a novel Boswellia serrata extract (5-Loxin(R)) enriched with 30% AKBA (US Patent 2004/0073060A1). The genetic basis of the anti-inflammatory effects of 5-Loxin(R) was explored in a system of TNFalpha-induced gene expression in human microvascular endothelial cells. 5-Loxin(R) significantly prevented the TNFalpha-induced expression of matrix metalloproteinases and adhesion molecules (ICAM-1 and VCAM-1), and inducible expression of the mediators of apoptosis. With such interesting findings, we planned to determine the broad-spectrum safety of 5-Loxin(R). Acute oral, acute dermal, primary skin and eye irritation, and dose-dependent 90-day subchronic toxicity studies were conducted. In safety studies, acute oral LD(50) of 5-Loxin(R) was found to be greater than 5,000 mg/kg in both male and female Sprague-Dawley rats. No changes in body weight or adverse effects were observed following necropsy. Acute dermal LD(50) of 5-Loxin(R) was found to be >2,000 mg/kg. Primary skin irritation test was conducted with 5-Loxin(R) on New Zealand Albino rabbits and 5-Loxin(R) was classified as nonirritating. Primary eye irritation test was conducted with 5-Loxin on rabbits and 5-Loxin(R) was classified as mildly irritating to the eye. A dose-dependent 90-day subchronic toxicity study demonstrated no significant changes in selected organ weights individually and as percentages of body and brain weights. 5-Loxin(R) supplementation did not cause changes in hepatic DNA fragmentation on 30, 60, or 90 days of treatment. Hematology, clinical chemistry, and histopathological evaluations did not show any adverse effects in all organs tested. Taken together, these results demonstrate the broad spectrum safety of 5-Loxin(R).
Toxicol Mech Methods. 2006;16(4):199-226.
PMID: 20021046 [PubMed - as supplied by publisher]
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| 28. |
Clastogenic effects of dietary supplement--Spirulina alga, and some medicinal plant products from Boswellia serrata, Withania somnifera on mice.
Ghoshal S, Mukhopadhyay MJ, Mukherjee A
Pretreatment of aqueous extracts of Zyrulina (Spirulina), Aswagandha (Withania) and Nopane (Boswellia) on colchicine induced chromosome damage showed weakness of clastogenic activity in Swiss albino mice. None of the treatments increased significantly the number of chromosome aberrations.
Indian J Exp Biol. 2001 Oct;39(10):1068-70.
PMID: 11883518 [PubMed - indexed for MEDLINE]
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