Pro-inflammatory cytokine molecules from Boswellia serrate suppresses lipopolysaccharides induced inflammation demonstrated in an in-vivo zebrafish larval model.
BACKGROUND: Boswellia serrate is an ancient and highly valued ayurvedic herb. Its extracts have been used in medicine for centuries to treat a wide variety of chronic inflammatory diseases. However, the mechanism by which B. serrata hydro alcoholic extract inhibited pro-inflammatory cytokines in zebrafish (Danio rerio) larvae with LPS-induced inflammation remained unknown.
Mol Biol Rep. 2022 Aug;49(8):7425-7435.
Incensole derivatives from frankincense: Isolation, enhancement, synthetic modification, and a plausible mechanism of their anti-depression activity.
Encouraged by the potent anti-depression activities of incensole (1) and incensole acetate (2) isolated from the resin of Boswellia papyrifera in our previous work, different derivatives of 1 and 2 were synthesized in the present study. The reaction of 1 with m-CPBA afforded the mono-epoxide derivative 3a, while the same reaction with 2 led to three different epoxide derivatives 3a, 3b, and 3c. Oxidation of 1 with PCC to get compound 3b, however along with the target 3b, the reaction gave three interesting side products (3c-3e). Oxime (3b-1) resulted from the reaction of 3b with hydroxylamine hydrochloride in pyridine, while epoxidation of 2 generate three epoxide products (4a-4c). The structures of all products were unambiguously confirmed using NMR and Mass spectrometry. Compounds 3a-e and 4a-c (0.1-3 mg/kg, i.p.) demonstrated promising anti-depression activities in classical mouse models of depression of FST and TST. The results showed that compounds 3a-e and 4a-c (0.1-3 mg/kg, i.p.) caused dose dependent reduction in immobility time compared to the vehicle control, with 3c-3e and 4b-4c demonstrating higher potency and efficacy. The findings of the open field test excluded the motor effects of these compounds, thus further confirming their anti-depression activity. Preliminary investigation into their mechanism of action using GABA antagonist, PTZ and molecular docking has predicted that compounds 3e and 4c bind at the GABA binding site of GABA receptor to produce GABAergic effects. Furthermore, the promising anti-depression potency of compounds 1 and 2 and their derivatives make them lead compounds for drug discovery.
Bioorg Chem. 2022 Sep;126():105900.
Boswellic Acids, Pentacyclic Triterpenes, Attenuate Oxidative Stress, and Bladder Tissue Damage in Cyclophosphamide-Induced Cystitis.
Boswellic acids, derived from the plant, have been demonstrated to have anti-inflammatory properties in experimental animal models. The present study was aimed to evaluate the uro-protective effect of boswellic acids in rats with cyclophosphamide-induced cystitis. Interstitial cystitis was induced by cyclophosphamide (CYP). In order to analyze the reduction of the urothelial damage, the bladder weight, the nociception response, and the Evans blue dye extravasation from the bladder were evaluated. To investigate the involvement of lipid peroxidation and enzymatic antioxidants CAT, SOD, and GPX and MPO and NO were evaluated. IL-6 and TNF-α were measured by the ELISA immunoassay technique. The results showed that pretreatment with boswellic acids significantly reduced urothelial damage which was accompanied by a decrease in the activity of MDA, CPO, and NO levels and prevention of the depletion of CAT, SOD, and GPX. The levels of IL-6 and TNF-α were dramatically reduced by boswellic acids. Histopathological findings revealed a considerable reduction in cellular infiltration, edema, epithelial denudation, and bleeding. Our findings showed that boswellic acids, by their antioxidant and anti-inflammatory properties, negate the detrimental effects of cyclophosphamide on the bladder, suggesting boswellic acids as promising therapeutic alternatives for cystitis.
ACS Omega. 2022 Apr;7(16):13697-13703.
Influence of Dietary Supplementation with and on Performance and Blood Biochemistry in Free-Range Leghorn Laying Hens.
This study was conducted to evaluate the safety and the beneficial effects of dietary supplementation with () and () in Leghorn hens during the critical pre-laying and laying phases. A total of 120 pullets, 17 weeks of age, were assigned to two groups (Control-C; Treated-T, = 60 each). For 12 weeks, the T group received a diet supplemented with 0.3% of dry extracts of (5%) and (5%). The study lasted 19 weeks. Productive performance, serum analytes, H/L ratio, IgA and anti-IBV antibodies were investigated. Water intake was significantly higher, while body and egg weight was significantly lower for the T group ( < 0.05). No other differences were detected in performance parameters, serum analytes, IgA and H/L ratio excluding t0, with a significantly ( < 0.05) higher H/R ratio and higher titers of anti-IBV antibody for the T group. Overall, the data obtained in this study show that the supplementation with and was safe and resulted in an increase in water consumption, a decrease in egg weight, and a sedative effect in the hens. In the future, it would be interesting to test this supplement in hens reared on intensive farms.
Vet Sci. 2022 Apr;9(4):.
Taxonomical Investigation, Chemical Composition, Traditional Use in Medicine, and Pharmacological Activities of Flueck.
Aromatic oleo-gum-resin secreted from , reputed as frankincense, is widely used in traditional medicine to treat Alzheimer's disease, gastric disorders, hepatic disorders, etc. Frankincense is also used in the cosmetic, perfume, and beverage and food industries. Frankincense is a rich resource for bioactive compounds, especially boswellic acids and derivatives. Although several reports have described frankincense's constituents and pharmacological activities, there is no comprehensive study that covers the valuable information on this species. Therefore, the current review will focus on the phytochemistry, traditional uses, and pharmacological activities of .
Evid Based Complement Alternat Med. 2022;2022():8779676.
New tirucallane-type triterpenoids from the resin of Boswellia carteriiand their NO inhibitory activities.
Six new tirucallane-type triterpenoids (1-6), along with ten known triterpenoids, were isolated from methylene chloride extract of the resin of Boswellia carterii Birdw. By the application of the comprehensive spectroscopic data, the structures of the compounds were clarified. The experimental electronic circular dichroism spectra were compared with those calculated, which allowed to assign the absolute configurations. Compounds 5 and 6 possesed a 2, 3-seco tirucallane-type triterpenoid skeleton, which were first reported. Their inhibitory activity against NO formation in LPS-activated BV-2 cells were evaluated. Compound 9 showed appreciable inhibitory effect, with an IC value of 7.58 ± 0.87 μmol·L.
Chin J Nat Med. 2021 Sep;19(9):686-692.
Cembranoids from Boswellia species.
Frankincense of Boswellia species has long been used in traditional medicines, mainly for its interesting anti-inflammatory and anti-depressant properties of its di- and triterpenes. Boswellic acids (triterpenes) and cembranoids (diterpenes) are the major constituents of frankincense from all reported species which are responsible for the overall biological activity of frankincense. Boswellic acids have been thoroughly investigated for decades but cembranoids have attracted considerable attention only recently, and a good number of publications have highlighted the important role of these 14-membered rings in contributing to the superior anti-inflammatory activity of the sacred resin. Partial and total syntheses of some cembranoids from frankincense have been reported. Their therapeutic potential is not limited to the well proven anti-inflammatory activity but also to their recently reported anti-depressant properties. There is a considerable number of publications in the field of cembranoids of Boswellia species where we feel a review in this topic will be of interest to the readership of Phytochemistry. In this article we have discussed the chemistry (isolation and chemical structures as well as synthetic studies), biogenesis and bioactivity of the reported cembranoids of Boswellia species. The structural discrepancies due to wrongly assigned structures of some cembranoids have been highlighted and corrected. We have covered the related literature up to the end of 2020.
Phytochemistry. 2021 Nov;191():112897.
[One new cembranoid diterpene from gum resin of Boswellia carterii].
This study aims to study the chemical components from the gum resin of Boswellia carterii. Five cembranoid diterpenes were isolated from the gum resin of B. carterii by various of column chromatographies including silica gel, Sephadex LH-20, and semi-preparative HPLC. Their structures were identified on the basis of physicochemical properties, mass spectrometry(MS), nuclear magnetic resonance(NMR), Ultraviolet(UV) and infrared(IR) spectroscopic data. These compounds were identified as(1S,2E,4R,5S,7E,11E)-4-methoxy-5-hydroxycembrane(1),(1R~*,4R~*,5E,8E,12E,15E)-4-hydroxycembra-5,8,12,15-tetraene(2), cembrene A(3),(3S,4S,7R)-4-hydroxycembrane(4), and pavidolide D(5). Compound 1 was a new compound. Compounds 2, 4, and 5 were obtained from the gum resin of B. carterii for the first time. Compound 2 showed weak inhibition on the human liver cancer cell line HepG2.
Zhongguo Zhong Yao Za Zhi. 2021 May;46(9):2215-2219.
Dietary Plant Extracts Improve the Antioxidant Reserves in Weaned Piglets.
Reducing the use of antibiotics in livestock in order to contain antibiotic resistance and studying natural substance additives are key to sustainability. Among the various biological activities of plant extracts, antioxidant activity plays an important role. The present study assesses the total antioxidant activity and antioxidant reserves using the Kit Radicaux Libres test (KRL™ Kirial International, Couternon, France). One hundred and sixty piglets (Topics × Tempo) weaned at 28 days of age were divided into four dietary treatment groups that were fed a commercial diet (the control group, C); 500 mg/kg extract (BOS); 200 and 50 mg/kg and extracts (UT) respectively; and 225 mg/kg of an antioxidant plant extract mixture (AOX). The blood antioxidant activity of the piglets was measured using the KRL test and the reserves were analyzed on whole blood samples after hydrolysis with glucosidase, sulfatase and glucuronidase. No significant differences were observed in growth performance. The delta KRL values of the whole blood showed a significantly higher total antioxidant status of the piglets from the BOS and AOX groups than the UT and C groups (+30.7 BOS; +27.7 AOX vs. +17.81 UT +13.30 C; = 0.002) between 18 and 28 days post-weaning. The delta KRL values of red blood cells (RBCs) showed a significantly higher total antioxidant status of the piglets from the AOX groups than the UT and BOS groups (+22.2 AOX; vs. +9.90 UT +9.4 BOS; = 0.016) between the two sampling times. Reserves of UT and AOX were higher than C and BOS for all enzymes, glucosides, sulphates, and glucuronides. The biological KRL test proved to be an extremely sensitive tool to evaluate the piglets' antioxidant status. Determining the antioxidant reserve also provides a better understanding of the real antioxidant status of pigs.
Antioxidants (Basel). 2021 Apr;10(5):.
Ameliorative Effects of Boswellic Acid on Fipronil-Induced Toxicity: Antioxidant State, Apoptotic Markers, and Testicular Steroidogenic Expression in Male Rats.
The study investigated the ability of boswellic acid (BA) to alleviate the testicular and oxidative injury FPN insecticide intoxication in the male rat model. Rats were randomly assigned to six equivalent groups (six rats each) as the following: control rats orally administered with 2 mL physiological saline/kg of body weight (bwt); boswellic acid (BA1) rats orally administered 250 mg BA/kg bwt; boswellic acid (BA2) rats orally administered 500 mg BA/kg bwt; fipronil (FPN) rats orally administered 20 mg FPN/kg bwt; (FPN + BA1) rats orally administered 20 mg FPN/kg bwt plus 250 mg BA/kg bwt, and (FPN + BA2) rats orally administered 20 mg FPN/kg bwt plus 500 mg BA/kg bwt. After 60 days, semen viability percentage and live spermatozoa percentage were decreased, and a considerably increased abnormality of the sperm cells in FPN-administered rats improved substantially with the co-administration of BA. BA had refinement of the histological architecture of testes and sexual glands. Quantitative analysis recorded a noticeable decline in the nuclear cell-proliferating antigen (PCNA) percentage area. FPN triggered cell damage, which was suggested by elevated malondialdehyde and interleukin 6, tumor necrosis factors alpha, and decreased glutathione level. Proapoptotic factor overexpression is mediated by FPN administration, while it decreased the antiapoptotic protein expression. Similarly, BA has shown significant upregulation in steroidogenic and fertility-related gene expression concerning the FPN group. Pathophysiological damages induced by FPN could be alleviated by BA's antioxidant ability and antiapoptotic factor alongside the upregulation of steroidogenic and fertility-related genes and regimented the detrimental effects of FPN on antioxidant and pro-inflammatory biomarkers.
Animals (Basel). 2021 Apr;11(5):.
In vitro anti-inflammatory and antioxidant activities of ZnFe O and CrFe O nanoparticles synthesized using Boswellia carteri resin.
The development of plant-based nano-materials is considered an eco-friendly technology because it does not involve hazardous chemicals. In this study, bimetallic ZnFe O and CrFe O nanoparticles were synthesized using an aqueous extract of Boswellia carteri resin. Synthesized ZnFe O and CrFe O nanoparticles were characterized by UV-Vis spectroscopy, FTIR, XRD, and HR-TEM. The anti-inflammatory activity was investigated in LPS-stimulated RAW 264.7 macrophages, whereas antioxidant activity was examined using a Hydrogen Peroxide Scavenging Activity Assay, Nitric Oxide Scavenging Activity Assay, and ABTS Radical Scavenging Assay. ZnFe O and CrFe O nanoparticles demonstrated a moderate scavenger of H O with IC values; 87.528 ± 8 μg/ml and 146.4468 ± 12 μg/ml, respectively. While they exhibited a strong scavenger of NO with IC values; 4.01 ± 0.7 μg/ml and 4.01 ± 0.7μg/ml, respectively. Interestingly, ZnFe O and CrFe O nanoparticles revealed an excellent anti-inflammatory activity by dose-dependently suppressing mRNA expressions of IL-1b, IL-6, and TNF-α. Also, ZnFe O and CrFe O nanoparticles suppress the protein expression of TNF-α. Together, our results proved that phyto-mediated ZnFe O and CrFe O nanoparticles using Boswellia carteri resin have great potential in biomedical applications such as anti-inflammatory and antioxidant. PRACTICAL APPLICATIONS: Our phyto-synthesized chromium iron oxide bimetallic nanoparticles (NPs) have shown a novel and potent anti-inflammatory activity, with remarkable biosafety toward tested macrophages. Zinc iron oxide bimetallic NPs exhibited anti-inflammatory effect with a lesser extent compared to the former, with moderate cytotoxicity against tested macrophages. Both zinc and chromium iron oxide NPs exhibited an equivalent antioxidant activity. Our resin-capped chromium iron oxide NPs are suggested to be a competing nonsteroidal anti-inflammatory agent; it is further recommended to establish advanced animal studies to confirm their biosafety, stability, and anti-inflammatory activity accompanied with the antioxidant activity.
J Food Biochem. 2021 Jun;45(6):e13730.
Sacraoxides A-G, Bioactive Cembranoids from Gum Resin of .
Seven undescribed cembranoids, sacraoxides A-G (-) were isolated from the gum resin of . Their structures were elucidated by extensive physicochemical and spectroscopic analysis, as well as ECD calculation, modified Mosher's method and X-ray diffraction crystallography. Compounds and exhibited inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in RAW264.7 cells with IC values of 24.9 ± 1.7 and 36.4 ± 2.9 M.
Front Chem. 2021;9():649287.
Biosynthetic diversity in triterpene cyclization within the Boswellia genus.
This review is not intended to describe the triterpenes isolated from the Boswellia genus, since this information has been covered elsewhere. Instead, the aim is to provide insights into the biosynthesis of triterpenes in Boswellia. This genus, which has 24 species, displays fascinating structural diversity and produces a number of medicinally important triterpenes, particularly boswellic acids. Over 300 volatile components have been reported in the essential oil of Boswellia, and more than 100 diterpenes and triterpenes have been isolated from this genus. Given that no triterpene biosynthetic enzymes have yet been isolated from any members of the Boswellia genus, this review will cover the likely biosynthetic pathways as inferred from structures in nature and the probable types of biosynthetic enzymes based on knowledge of triterpene biosynthesis in other plant species. It highlights the importance of frankincense and the factors and threats affecting its production. It covers triterpene biosynthesis in the genus Boswellia, including dammaranes, tirucallic acids, lupanes, oleananes, ursanes and boswellic acids. Strategies for elucidating triterpene biosynthetic pathways in Boswellia are considered. Furthermore, the possible mechanisms behind wound-induced resin synthesis by the tree and related gene expression profiling are covered. In addition, the influence of the environment and the genotype on the biosynthesis of resin and on variations in the compositions and types of resins will also be reviewed.
Phytochemistry. 2021 Apr;184():112660.
Phyto-Facilitated Bimetallic ZnFeO Nanoparticles via Boswellia carteri: Synthesis, Characterization, and Anti-Cancer Activity.
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.
Anticancer Agents Med Chem. 2021;21(13):1767-1772.
Boswellic acids and their derivatives as potent regulators of glucocorticoid receptor actions.
Glucocorticoid (GCs) hormones exert their actions via their cognate steroid receptors the Glucocorticoid Receptors (GR), by genomic or non-genomic mechanisms of actions. GCs regulate many cellular functions among them growth, metabolism, immune response and apoptosis. Due to their cell type specific induction of apoptosis GCs are used for the treatment of certain type of cancer. In addition, due to their anti-inflammatory actions, GCs are among the most highly prescribed drug to treat chronic inflammatory disorders, albeit to the many adverse side effects arising by their long term and high doses use. Thus, there is a high need for selective glucocorticoid receptor agonist - modulators (SEGRA- SGRMs) as effective as classic GCs, but with a reduced side effect profile. Boswellic acids (BAs) are triterpenes that show structural similarities with GCs and exhibit anti-inflammatory and anti-cancer activities. In this study we examined whether BA alpha and beta and certain BAs derivatives exert their actions, at least in part, through the regulation of GR activities. Applying docking analysis we found that BAs can bind stably into the deacylcortivazol (DAC) accommodation pocket of GR. Moreover we showed that certain boswellic acids derivatives induce glucocorticoid receptor nuclear translocation, no activation of GRE dependent luciferase gene expression, and suppression of the TNF-α induced NF-κB transcriptional activation in GR positive HeLa and HEK293 cells, but not in low GR level COS-7 cells. Furthermore, certain boswellic acids compounds exert antagonistic effect on the DEX-induced GR transcriptional activation and induce cell type specific mitochondrial dependent apoptosis. Our results indicate that certain BAs are potent selective glucocorticoid receptor regulators and could have great potential for therapeutic use.
Arch Biochem Biophys. 2020 Nov;695():108656.
Roles of ethylene, jasmonic acid, and salicylic acid and their interactions in frankincense resin production in Boswellia sacra Flueck. trees.
The roles of ethylene, jasmonic acid, and salicylic acid and their interactions in frankincense resin production in Boswellia sacra trees growing in the drylands of Oman were studied. On March 18 (Experiment 1) and September 17 (Experiment 2), 2018, 32-year-old B. sacra trees with multiple trunks were selected at the Agricultural Experiment Station, Sultan Qaboos University, Oman. Various lanolin pastes containing Ethrel, an ethylene-releasing compound; methyl jasmonate; sodium salicylate; and combinations of these compounds were applied to debarked wounds 15 mm in diameter on the trunks. After a certain period, the frankincense resin secreted from each wound was harvested and weighed. The anatomical characteristics of the resin ducts were also studied in the bark tissue near the upper end of each wound. The combination of Ethrel and methyl jasmonate greatly enhanced frankincense resin production within 7 days in both seasons. The application of methyl jasmonate alone, sodium salicylate alone or a combination of both did not affect resin production. These findings suggest a high possibility of artificial enhancement of frankincense resin production by the combined application of Ethrel and methyl jasmonate to B. sacra trees.
Sci Rep. 2020 Oct;10(1):16760.
Bioactive cembrane diterpenoids from the gum resin of Boswellia carterii.
Eight new cembrane-type diterpenoids, boscartins AP-AW (1-8) were obtained from the gum resin of Boswellia carterii. Among which, six ones (2-7) were isomers, with one hydroxy group and two double bonds migrating along the carbocycle. The structures were elucidated by spectroscopic examination. All isolates were evaluated for anti-inflammatory activity and hepatoprotective activity by cell models of LPS-induced RAW 264.7 mouse peritoneal macrophages and APAP-induced HepG2 cells, respectively. As for anti-inflammatory activity assay, compound 1 exhibited potent activity against NO production (IC of 13.1 μM), with the other ones exhibiting weak anti-inflammatory activity (IC > 50 μM). As for hepatoprotective activity assay, compound 1 exhibited more significant activity (inhibition rate of 30.7%) than that of the positive control (bicyclol, inhibition rate of 27.2%), and compounds 4, and 6 showed nearly the same activities as the control (inhibition rates of 26.7% and 25.9%, respectively), with the other ones exhibiting weak hepatoprotective activity.
Fitoterapia. 2020 Oct;146():104699.
Triterpenic Acids as Non-Competitive α-Glucosidase Inhibitors from with Structure-Activity Relationship: In Vitro and In Silico Studies.
Fourteen triterpene acids, viz., three tirucallane-type (-), eight ursane-type (-), two oleanane-type (, ) and one lupane type (), along with boswellic aldehyde (), α-amyrine (), epi-amyrine (), straight chain acid (), sesquiterpene () and two cembrane-type diterpenes (, ) were isolated, first time, from the methanol extract of resin. Compound () was isolated for first time as a natural product, while the remaining compounds (‒) were reported for first time from The structures of all compounds were confirmed by advanced spectroscopic techniques including mass spectrometry and also by comparison with the reported literature. Eight compounds (- and ) were further screened for in vitro α-glucosidase inhibitory activity. Compounds - and showed significant activity against α-glucosidase with IC values ranging from 9.9-56.8 μM. Compound (IC = 9.9 ± 0.48 μM) demonstrated higher inhibition followed by (IC = 14.9 ± 1.31 μM), (IC = 20.9 ± 0.05 μM) and (IC = 56.8 ± 1.30 μM), indicating that carboxylic acid play a key role in α-glucosidase inhibition. Kinetics studies on the active compounds - and were carried out to investigate their mechanism (mode of inhibition and dissociation constants ). All compounds were found to be non-competitive inhibitors with values in the range of 7.05 ± 0.17-51.15 ± 0.25 µM. Moreover, in silico docking was performed to search the allosteric hotspot for ligand binding which is targeted by our active compounds investigates the binding mode of active compounds and it was identified that compounds preferentially bind in the allosteric binding sites of α-glucosidase. The results obtained from docking study suggested that the carboxylic group is responsible for their biologic activities. Furthermore, the α-glucosidase inhibitory potential of the active compounds is reported here for the first time.
Biomolecules. 2020 May;10(5):.
Structural and mechanistic insights into 5-lipoxygenase inhibition by natural products.
Leukotrienes (LT) are lipid mediators of the inflammatory response that are linked to asthma and atherosclerosis. LT biosynthesis is initiated by 5-lipoxygenase (5-LOX) with the assistance of the substrate-binding 5-LOX-activating protein at the nuclear membrane. Here, we contrast the structural and functional consequences of the binding of two natural product inhibitors of 5-LOX. The redox-type inhibitor nordihydroguaiaretic acid (NDGA) is lodged in the 5-LOX active site, now fully exposed by disordering of the helix that caps it in the apo-enzyme. In contrast, the allosteric inhibitor 3-acetyl-11-keto-beta-boswellic acid (AKBA) from frankincense wedges between the membrane-binding and catalytic domains of 5-LOX, some 30 Å from the catalytic iron. While enzyme inhibition by NDGA is robust, AKBA promotes a shift in the regiospecificity, evident in human embryonic kidney 293 cells and in primary immune cells expressing 5-LOX. Our results suggest a new approach to isoform-specific 5-LOX inhibitor development through exploitation of an allosteric site in 5-LOX.
Nat Chem Biol. 2020 Jul;16(7):783-790.
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.
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.
Structure-Activity Relationships of Pentacyclic Triterpenoids as Inhibitors of Cyclooxygenase and Lipoxygenase Enzymes.
Pentacyclic triterpenes may be active agents and provide a rich natural resource of promising compounds for drug development. The inhibitory activities of 29 natural oleanane and ursane pentacyclic triterpenes were evaluated against four major enzymes involved in the inflammatory process: 5-LOX, 15-LOX-2, COX-1, and COX-2. It was found that 3--acetyl-β-boswellic acid potently inhibited human 15-LOX-2 (IC = 12.2 ± 0.47 μM). Analysis of the structure-activity relationships revealed that the presence of a hydroxy group at position 24 was beneficial in terms of both 5-LOX and COX-1 inhibition. Notably, the introduction of a carboxylic acid group at position 30 was important for dual 5-LOX/COX inhibitory activity; furthermore, its combination with a carbonyl group at C-11 considerably increased 5-LOX inhibition. Also, the presence of an α-hydroxy group at C-2 or a carboxylic acid group at C-23 markedly suppressed the 5-LOX activity. The present findings reveal that the types and configurations of polar moieties at positions C-2, -3, -11, -24, and -30 are important structural aspects of pentacyclic triterpenes for their potential as anti-inflammatory lead compounds.
J Nat Prod. 2019 Dec;82(12):3311-3320.
Chemical Composition of the Oleogum Resin Essential Oils of from Burkina Faso.
Frankincense, the oleogum resin from members of , has been used as medicine and incense for thousands of years, and essential oils derived from frankincense are important articles of commerce today. A new source of frankincense resin, from West Africa has been presented as a new, alternative source of frankincense. In this work, the oleogum resins from 20 different trees growing in Burkina Faso, West Africa were collected. Hydrodistillation of the resins gave essential oils that were analyzed by GC-MS and GC-FID. The essential oils were dominated by α-pinene (21.0%-56.0%), followed by carvone (2.1%-5.4%) and α-copaene (1.8%-5.0%). Interestingly, there was one individual tree that, although rich in α-pinene (21.0%), also had a substantial concentration of myrcene (19.2%) and α-thujene (9.8%). In conclusion, the oleogum resin essential oil compositions of , rich in α-pinene, are comparable in composition to other frankincense essential oils, including , , and . Additionally, the differences in composition between samples from Burkina Faso and those from Nigeria are very slight. There is, however, a rare chemotype of that is dominated by myrcene, found both in Burkina Faso as well as Nigeria.
Plants (Basel). 2019 Jul;8(7):.
Isolation, structure elucidation, and immunostimulatory activity of polysaccharide fractions from Boswellia carterii frankincense resin.
Frankincense has a long history in religious, cultural, and medicinal use. In this study polysaccharides were extracted from frankincense from Boswellia carterii. The polysaccharides were purified by anion exchange chromatography on a DEAE-Sepharose Fast Flow 16/10 FPLC column. Six fractions were obtained and the three most active immunomodulatory fractions were further purified by size exclusion chromatography on a Superdex-200 column. The composition showed the monosaccharides present were predominantly galactose, arabinose, and glucuronic acid along with small amounts of rhamnose and glucose. The monosaccharide composition and glycosyl linkage analysis revealed the polysaccharides belong to the type II arabinogalactans. Fourier-transform infrared spectroscopy and bicinchoninic acid assay showed that the amount of protein in the samples was <1 wt%. One-dimensional H NMR were consistent with high molecular weight compounds. The monosaccharides were primarily in the β conformation. The three fractions exhibited an immunostimulatory effect on RAW 264.7 murine macrophage cells. The most active immunostimulatory fraction FA2, stimulated a range of pro-inflammatory mediators including iNOS, NO, TNF-α, and IL-6 in RAW 264.7 cells. The fractions were effective in proliferating primary murine splenocytes. The results indicate that the polysaccharides isolated from frankincense have the potential to be used as an immunological stimulant or nutraceutical.
Int J Biol Macromol. 2019 Jul;133():76-85.
New derivatives of 11-keto-β-boswellic acid (KBA) induce apoptosis in breast and prostate cancers cells.
A series of new 11-keto-β-boswellic acid were partially-synthesized by modifying the hydroxyl and carboxylic acid functional groups of ring A. The structures of the new analogs were confirmed by detailed spectral data analysis. Compounds , and exhibited potent anti-cancer results against two human tumor cancer cell lines having IC value of MCF-7 (breast) and LNCaP (prostate): 123.6, 9.6 and 88.94 μM and 9.6, 44.12 and 12.03 μM, respectively. Additionally, a maximum nuclear fragmentation was observed for (78.44%) in AKBA treated cells after 24 hr followed by and with (74.25 and 66.9% respectively). This study suggests that the presence of hydrazone functionality ( and ) has effectively improved the potency of AKBA. Interestingly, compound with a lost carboxylic acid group of ring A showed comparable potent activity. Highly selective AKBA requires further modification to improve its bioavailability and solubility inside the cancer cells.
Nat Prod Res. 2021 Mar;35(5):707-716.
Synthesis of new boswellic acid derivatives as potential antiproliferative agents.
In the current investigation, a series of heterocyclic derivatives of boswellic acids were prepared along with new monomers of 3--acetyl-11-keto-β-boswellic acid (AKBA, ) 11-keto-β-boswellic acid (KBA, ) and several new bis-AKBA and KBA homodimers and AKBA-KBA heterodimers. The effects of these compounds on the proliferation of different human cancer cell lines, viz., FaDu (pharynx carcinoma), A2780 (ovarian carcinoma), HT29 (colon adenocarcinoma), and A375 (malignant melanoma), have been evaluated. Thus, KBA homodimer effectively inhibited the growth of FaDu, A2780, HT29, and A375 cells with EC values below 9 μM. In addition, compounds , , , , , and also exhibited cytotoxic effects for A2780, HT29, and A375 cancer cells. In particular, the pyrazine analog was highly cytotoxic for A375 cancer cells with an EC value of 2.1 μM.
Nat Prod Res. 2020 Jul;34(13):1845-1852.
Frankincense, the oleo-gum resin of trees, has been used in traditional medicine since ancient times. Frankincense has been used to treat wounds and skin infections, inflammatory diseases, dementia, and various other conditions. However, in many cases, the biomolecular targets for frankincense components are not well established. In this work, we have carried out a reverse docking study of diterpenoids and triterpenoids with a library of 16034 potential druggable target proteins. diterpenoids showed selective docking to acetylcholinesterase, several bacterial target proteins, and HIV-1 reverse transcriptase. triterpenoids targeted the cancer-relevant proteins (poly(ADP-ribose) polymerase-1, tankyrase, and folate receptor β), inflammation-relevant proteins (phospholipase A2, epoxide hydrolase, and fibroblast collagenase), and the diabetes target 11β-hydroxysteroid dehydrogenase. The preferential docking of terpenoids is consistent with the traditional uses and the established biological activities of frankincense.
Medicines (Basel). 2018 Aug;5(3):.
Mol Cancer Res. 2018 Sep;16(9):1444.
Design, synthesis and biological evaluation of ring A modified 11-keto-boswellic acid derivatives as Pin1 inhibitors with remarkable anti-prostate cancer activity.
Pin1 (Protein interaction with never in mitosis A1) is a validated molecular target for anticancer drug discovery. Herein, we reported the design, synthesis, and structure-activity relationship study of novel ring A modified AKBA (3-acetyl-11-keto-boswellic acid) derivatives as Pin1 inhibitors. Most compounds showed superior Pin1 inhibitory activities to AKBA. One of the most promising compounds, 10a, potently inhibited Pin1 with IC value of 0.46 μM, while it displayed excellent anti-proliferative effect against prostate cancer cells PC-3 with GI value of 1.82 μM. Structure-activity relationship indicated that reasonable structural modifications in ring A had significant impact on improving activity. Further mechanism research revealed that 10a decreased the level of Cyclin D1 and caused cell cycle arrest at G0/G1 phase in PC-3 cancer cells. Thus, compound 10a may serve as potential anti-prostate cancer agent for further investigation through Pin1 inhibition.
Bioorg Med Chem Lett. 2018 Oct;28(19):3187-3193.
Chemical, molecular and structural studies of Boswellia species: β-Boswellic Aldehyde and 3-epi-11β-Dihydroxy BA as precursors in biosynthesis of boswellic acids.
The distribution and biosynthesis of boswellic acids (BAs) is scarce in current literature. Present study aims to elucidate the BAs biosynthetic and its diversity in the resins of Boswellia sacra and Boswellia papyrifera. Results revealed the isolation of new (3β, 11β-dihydroxy BA) and recently known (as new source, β-boswellic aldehyde) precursors from B. sacra resin along with α-amyrin. Following this, a detailed nomenclature of BAs was elucidated. The quantification and distribution of amyrins (3-epi-α-amyrin, β-amyrin and α-amyrin) and BAs in different Boswellia resins showed highest amyrin and BAs in B. sacra as compared with B. serrata and B. papyrifera. Distribution of BAs significantly varied in the resin of B. sacra collected from dry mountains than coastal trees. In B. sacra, high content of α-amyrin was found in the roots but it lacked β-amyrin and BAs. The leaf part showed traces of β-ABA and AKBA but was deficient in amyrins. This was further confirmed by lack of transcript accumulation of amyrin-related biosynthesis gene in leaf part. In contrast, the stem showed presence of all six BAs which are attributed to existence of resin-secretory canals. In conclusion, the boswellic acids are genus-specific chemical constituents for Boswellia species albeit the variation of the amounts among different Boswellia species and grades.
PLoS One. 2018;13(6):e0198666.
Optimal Processing Conditions of Birdw. Using Response Surface Methodology.
BACKGROUND: Bridw. is being widely used for its anti-inflammatory properties, as well as for wound healing, antimicrobial, and immunomodulatory properties, and boswellic acids (BAs) are considered to be the main active constituents.
Pharmacogn Mag. 2018;14(54):235-241.
New α-Glucosidase inhibitors from the resins of Boswellia species with structure-glucosidase activity and molecular docking studies.
Phytochemical investigation of the oleo-gum resins from Boswellia papyrifera afforded one new triterpene, named 3α-hydroxyurs-5:19-diene (1) together with twelve known compounds including eight triterpenoids (2-9), two diterpenoids (10 and 11) and two straight chain alkanes (12 and 13). Similarly ten more known compounds were isolated from the resin of Boswellia sacra including one triterpene (20) and nine boswellic acids (14-19 and 21-23). Herein the compound 2 was first time reporting from natural source along with complete NMR assignment, while compounds 3-11 are known, but reported for the first time from the resin of B. papyrifera. The structure elucidation was done by advance spectroscopic D and D NMR techniques viz., H, C, DEPT, HSQC, HMBC, and COSY, and NEOSY, ESI-MS and compared with the reported literature. All compounds were evaluated for their α-glucosidase inhibitory activity and as result eight of them 1, 3, 10, 11, 15, and 17-19 were found significantly active against α-glucosidase with an IC value ranging from 15.0 ± 0.84 to 80.3 ± 2.33 µM, while 21 exhibited moderate activity with IC of 799.9 ± 4.98 µM. Furthermore, two compounds 24 and 25 were synthesised from 16 and 17 to see the effect of carboxyl group in structural-activity relationship (SAR) study. Compounds 24 and 25 retained good α-glucosidase inhibition as compared to 16 and 17, indicating that carboxylic group play a key role in SAR. In addition, the aforementioned activity of all the active compounds was first time reported for their α-glucosidase inhibition potential. The molecular docking studies showed that all the active compounds well accommodate in the active site of the enzyme. Moreover pharmacokinetic properties of the compounds were predicted in silico, suggesting that the compounds possess drug like properties and excellent ADMET profile.
Bioorg Chem. 2018 Sep;79():27-33.
Frankincense oleoresin has been used in traditional medicine for more than 5000 years. The phytochemistry of frankincense (Boswellia spp.) resins includes triterpenoids (including boswellic acids and their derivatives), diterpenoids (cembrenoids and cneorubenoids), and essential oils. The macrocyclic cembrene diterpenoids may play a part in the biological activities of frankincense resin, but neither the biological targets nor the modes of interaction with the targets are currently known. How these macrocycles interact with biological macromolecules likely depends on what conformation(s) are energetically available to them. In this work, a conformational analysis of 15 Boswellia cembrene diterpenoids and 1 verticillane diterpenoid was carried out at the B3LYP/6-31G* and M06-2X/6-31G* levels of theory, including the SM8 aqueous solvation model. The lowest-energy conformations of boscartin B and incensole oxide were the same as the previously reported X-ray crystal structures, while the lowest-energy conformations of boscartins A and C were very similar to the crystal structures. Boscartins D-H and isoincensole oxide showed only one low-energy conformation for each compound and are predicted to be conformationally locked. Incensole, isoincensolol, and serratol are predicted to be conformationally mobile with several low-energy forms. The conformational mobility of Boswellia cembrenoid diterpenoids depends largely on the degree of epoxidation, either oxirane or tetrahydrofuran rings.
J Mol Model. 2018 Mar;24(3):74.
Chemical Composition and Monoterpenoid Enantiomeric Distribution of the Essential Oils from Apharsemon (Commiphora gileadensis).
(Hebrew: apharsemon) has been used since Biblical times to treat various ailments, and is used today in the traditional medicine of some Middle Eastern cultures. The essential oils from the stem bark, leaves, and fruits of -collected at the Ein Gedi Botanical Garden, Israel-were obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry. In addition, the enantiomeric distributions of the monoterpenoids in the essential oils have been determined by chiral gas chromatography. The essential oils were dominated by monoterpene hydrocarbons, followed by oxygenated monoterpenoids. The major components in oils were the monoterpenes α-pinene (11.1-18.4%), sabinene (15.8-35.9%), β-pinene (5.8-18.0%), -cymene (4.8-8.4%), limonene (1.3-6.2%), γ-terpinene (0.7-8.1%), and terpinen-4-ol (5.3-18.5%). The (-)-enantiomers predominated for α-pinene, sabinene, β-pinene, limonene, and terpinen-4-ol. The chemical compositions of the essential oils from Israel are markedly different from previously reported samples, which were rich in sesquiterpenoids. Likewise, the enantiomeric distribution of monoterpenoids is very different from spp. essential oils.
Medicines (Basel). 2017 Sep;4(3):.
New water soluble glycosides of 11-keto-β-boswellic acid: A paradigm.
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.
Extraction and purification of five terpenoids from olibanum by ultrahigh pressure technique and high-speed countercurrent chromatography.
Five terpenoids, including two new ones, 3,7-dioxo-tirucalla-8,24-dien-21-oic acid (2) and 3α-acetoxyl-7-oxo-tirucalla-8,24-dien-21-oic acid (3), and three known ones, boscartol A (1), 11-keto-β-boswellic acid (4), and acetyl-11-keto-boswellic acid (5), have been extracted by the ultrapressure extraction and purified by pH-zone-refining countercurrent chromatography and high-speed countercurrent chromatography from olibanum. For ultrapressure extraction, the optimal condition including 200 MPa of extraction pressure, ethyl acetate of extraction solvent, 1:20 (g/mL) of solid/liquid ratio, and 2 min of extraction time were obtained. For the separation, from 1.5 g of the terpenoid extract, 220.1 mg of 4, 255.5 mg of 5, and 212.3 mg of the mixture of 1, 2, and 3 were obtained by pH-zone-refining countercurrent chromatography under the solvent system of chloroform/ethyl acetate/methanol/water (3:1:3:2, v/v/v/v) with aqueous ammonia and trifluoroacetic acid as retention and eluter agents. The enriched mixture (210 mg) was further separated by conventional high-speed countercurrent chromatography with petroleum ether/ethyl acetate/methanol/water (1:0.8:1.1:0.6, v/v/v/v), yielding 30.1 mg of 1, 35.5 mg of 2, 12.3 mg of 3. The structures of these five terpenoids were elucidated by extensive spectroscopic methods.
J Sep Sci. 2017 Jul;40(13):2732-2740.
Synthesis of new analogs of AKBA and evaluation of their anti-inflammatory activities.
A new series of 11-keto-β-boswellic acid and 3-O-acetyl-11-keto-β-boswellic acid analogs (5, 7, 8, 10, 13, 18a-d, 27a-c, 28a-d) were synthesized by modification of hydroxyl and acid functional moieties of boswellic acids. The structures of these analogs were confirmed by spectral data analysis (H, C NMR and mass). Compounds 18b, 27a and 8 showed potent 5-lipoxygenase enzyme inhibitory activity (IC: 19.53, 20.31 and 44.14μg/mL). The computational studies revealed that selectivity of AKBA is due to its fitment into the 5-LOX receptor, which is missing for the other enzymes like 12-LOX, COX-1 and COX-2. Our study found potentiating effects of 2-formyl and 3-keto substituents in reviving inactive AKBA analogues possessing essential COOH group at 4th position.
Bioorg Med Chem. 2017 Feb;25(4):1374-1388.
Design and synthesis of novel 2-substituted 11-keto-boswellic acid heterocyclic derivatives as anti-prostate cancer agents with Pin1 inhibition ability.
A series of novel acetyl-11-keto-β-boswellic acid (AKBA) derivatives with a different electron-withdrawing group on ring A and a nitrogen heterocycle at C-24 were designed and synthesized. These semi-synthetic compounds showed improved anti-proliferative activity against prostate cancer cells over AKBA. Compound 8f bearing 2-cyano-3,11-dioxo moiety and piperazine was the most potent to inhibit growth of prostate cancer PC-3 (IC = 0.04 μM) and LNCaP (IC = 0.27 μM) cell lines. 8f caused cell cycle arrest in G2/M and induced apoptosis. 8f decreased the protein levels of anti-apoptosis protein Mcl-1, c-FLIP and cell cycle regulating protein cyclin D1. 8f inhibited the activity of Pin1, a peptidyl-prolyl cis-trans isomerase to stabilize cyclin D1. 8f represented a compound with improved anti-proliferative effects for prostate cancer therapy working through new mechanisms.
Eur J Med Chem. 2017 Jan;126():910-919.
Ring A-modified Derivatives from the Natural Triterpene 3-O-acetyl-11-keto-β-Boswellic Acid and their Cytotoxic Activity.
BACKGROUND: Natural triterpene boswellic acids (BAs) have attracted much interest due to their anticancer activity, but more chemical modification is necessary to explore their pharmacological value. In addition to subtle functionalization, transformations that alter the triterpene skeleton are viewed as an alternative approach.
Anticancer Agents Med Chem. 2017;17(8):1153-1167.
Chemical constituents from twigs of Euonymus alatus.
To investigate the chemical compounds from the twigs of Euonymus alatus, nine compounds were isolated and identified as(+)-delta(2,11)-enaminousnic acid(1), 11-keto-beta-boswellic acid(2), acetyl 11-keto-beta-boswellic acid(3), camaldulenic acid(4), betulinic acid(5), 6beta-hydroxy-stigmast-4-en-3-one(6), 5-hydroxy-6,7-dimethoxyflavone(7), ethyl 2,4-dihydroxy-6-methylbenzoate(8), 4,4'-dimethoxy-1,1'-biphenyl(9). Their structures were elucidated by extensive spectroscopic analysis. Among them, compound 1 was a new natural product. Compounds 2-4 and 7-9 were obtained from the Euonymus genus for the first time. In vitro study showed that compounds 2 and 3 showed significant anti-tumor activities to BEL-7402 and HCT-8 at the concentration of 10 mg x L(-1). The inhibition rate of compound 2 was 61.78% and 68.29%, whereas the inhibition rate of compound 3 had reached to 70.91% and 84.07%.
Zhongguo Zhong Yao Za Zhi. 2015 Jul;40(13):2612-6.
Synthesis of β-boswellic acid derivatives as cytotoxic and apoptotic agents.
A series of β-boswellic acid derivatives were synthesized and evaluated for anticancer activity. One of the lead analog 4f displayed significant anticancer activity against a panel of cancer cells as well as substantially inhibited colony formation in HCT-116 cells. Furthermore, 4f was found to be a potent inducer of apoptosis confirmed by loss of mitochondrial membrane potential, DAPI staining, Western blotting and ROS generation.
Bioorg Med Chem Lett. 2016 Jan;26(1):76-81.
Combination of quantitative analysis and chemometric analysis for the quality evaluation of three different frankincenses by ultra high performance liquid chromatography and quadrupole time of flight mass spectrometry.
Frankincense has gained increasing attention in the pharmaceutical industry because of its pharmacologically active components such as boswellic acids. However, the identity and overall quality evaluation of three different frankincense species in different Pharmacopeias and the literature have less been reported. In this paper, quantitative analysis and chemometric evaluation were established and applied for the quality control of frankincense. Meanwhile, quantitative and chemometric analysis could be conducted under the same analytical conditions. In total 55 samples from four habitats (three species) of frankincense were collected and six boswellic acids were chosen for quantitative analysis. Chemometric analyses such as similarity analysis, hierarchical cluster analysis, and principal component analysis were used to identify frankincense of three species to reveal the correlation between its components and species. In addition, 12 chromatographic peaks have been tentatively identified explored by reference substances and quadrupole time-of-flight mass spectrometry. The results indicated that the total boswellic acid profiles of three species of frankincense are similar and their fingerprints can be used to differentiate between them.
J Sep Sci. 2015 Oct;38(19):3324-30.
Synthesis and biological evaluation of boswellic acid-NSAID hybrid molecules as anti-inflammatory and anti-arthritic agents.
Methyl esters of the β-boswellic acid (BA) and 11-keto-β-boswellic acid (KBA) obtained from Boswellia serrata resin were subjected to Steglich esterification with the different non-steroidal anti-inflammatory drugs (NSAID) viz., ibuprofen, naproxen, diclophenac and indomethacin. The novel hybrids of methyl boswellate (5-8) and that of methyl 11-keto boswellate (9-12) were evaluated for anti-inflammatory activity by carrageenan-induced rat hind paw edema model and anti-arthritic activity by Complete Freund's Adjuvant (CFA) induced arthritis in Wister albino rat. Significant inhibition on carrageenan-induced paw edema has been observed with 5, 6 and 10 where as in CFA induced rats, hybrids 5, 8, 9 and 12 exhibited pronounced antiarthritic activity. Hybrid molecules 5 and 9 have been found to be more effective in inhibiting in-vivo COX-2 than ibuprofen by itself, thus showing the synergistic effect. Hybrid 5 and 9 tested for in-vitro lipoxygenase and cyclooxygenase-2 (LOX/COX-2) inhibitory activity. The studies revealed that both 5 and 9 inhibited COX-2 relatively better than LOX enzyme.
Eur J Med Chem. 2015 Jun;98():170-8.
Prediction of anticancer property of bowsellic acid derivatives by quantitative structure activity relationship analysis and molecular docking study.
CONTEXT: Boswellic acid consists of a series of pentacyclic triterpene molecules that are produced by the plant Boswellia serrata. The potential applications of Bowsellic acid for treatment of cancer have been focused here.
J Pharm Bioallied Sci. 2015;7(1):21-5.
Synthesis and antitumor activity of ring A modified 11-keto-β-boswellic acid derivatives.
Beta-boswellic acids are interesting triterpenoic acids that show different biological activities. Their cytotoxic potential, as well as that of their derivates remained unexploited so far. In this study we were able to prepare derivatives of 11-keto-β-boswellic acid that showed lower IC50 values as determined by a sulphorhodamine B (SRB) assay using several different human tumour cell lines. Thus, the introduction of an amino group at position C-2 led to a significantly improved cytotoxic activity of amine 18. An apoptotic effect of compound 18 was determined using DNA laddering and trypan blue staining experiments.
Eur J Med Chem. 2015 Mar;92():700-11.
Genomic sequencing and microsatellite marker development for Boswellia papyrifera, an economically important but threatened tree native to dry tropical forests.
Microsatellite (or simple sequence repeat, SSR) markers are highly informative DNA markers often used in conservation genetic research. Next-generation sequencing enables efficient development of large numbers of SSR markers at lower costs. Boswellia papyrifera is an economically important tree species used for frankincense production, an aromatic resinous gum exudate from bark. It grows in dry tropical forests in Africa and is threatened by a lack of rejuvenation. To help guide conservation efforts for this endangered species, we conducted an analysis of its genomic DNA sequences using Illumina paired-end sequencing. The genome size was estimated at 705 Mb per haploid genome. The reads contained one microsatellite repeat per 5.7 kb. Based on a subset of these repeats, we developed 46 polymorphic SSR markers that amplified 2-12 alleles in 10 genotypes. This set included 30 trinucleotide repeat markers, four tetranucleotide repeat markers, six pentanucleotide markers and six hexanucleotide repeat markers. Several markers were cross-transferable to Boswellia pirrotae and B. popoviana. In addition, retrotransposons were identified, the reads were assembled and several contigs were identified with similarity to genes of the terpene and terpenoid backbone synthesis pathways, which form the major constituents of the bark resin.
AoB Plants. 2015 Jan;7():.
Design, synthesis and biological evaluation of β-boswellic acid based HDAC inhibitors as inducers of cancer cell death.
The synthesis and bio-evaluation of naturally occurring boswellic acids (BAs) as an alternate CAP for the design of new HDAC inhibitors is described. All the compounds were screened against a panel of human cancer cell lines to identify leads, which were subsequently examined for their potential to inhibit HDACs. The identified lead compound showed IC50 value of 6μm for HDACs, found to induce G1 cell cycle arrest at significantly low concentration (1μM) and caused significant loss in mitochondrial membrane potential at 5 and 10μM. Furthermore, specific interactions of the lead molecule inside the catalytic domain were also studied through in silico molecular modeling.
Bioorg Med Chem Lett. 2014 Oct;24(19):4729-4734.
Evid Based Complement Alternat Med. 2014;2014():605304.
Micropropagation and non-steroidal anti-inflammatory and anti-arthritic agent boswellic acid production in callus cultures of Boswellia serrata Roxb.
Micropropagation through cotyledonary and leaf node and boswellic acid production in stem callus of a woody medicinal endangered tree species Boswellia serrata Roxb. is reported. The response for shoots, roots and callus formation were varied in cotyledonary and leafy nodal explants from in vitro germinated seeds, if inoculated on Murshige and Skoog's (MS) medium fortified with cytokinins and auxins alone or together. A maximum of 8.0 ± 0.1 shoots/cotyledonary node explant and 6.9 ± 0.1 shoots/leafy node explants were produced in 91 and 88 % cultures respectively on medium with 2.5 μM 6-benzyladenine (BA) and 200 mg l(-1) polyvinylpyrrolidone (PVP). Shoots treated with 2.5 μM IBA showed the highest average root number (4.5) and the highest percentage of rooting (89 %). Well rooted plantlets were acclimatized and 76.5 % of the plantlets showed survival upon transfer to field conditions. Randomly amplified polymorphic DNA (RAPD) analysis of the micropropagated plants compared with mother plant revealed true-to-type nature. The four major boswellic acid components in calluses raised from root, stem, cotyledon and leaf explants were analyzed using HPLC. The total content of four boswellic acid components was higher in stem callus obtained on MS with 15.0 μM IAA, 5.0 μM BA and 200 mg l(-1) PVP. The protocol reported can be used for conservation and exploitation of in vitro production of medicinally important non-steroidal anti-inflammatory metabolites of B. serrata.
Physiol Mol Biol Plants. 2013 Jan;19(1):105-16.
11α-Ethoxy-β-boswellic acid and nizwanone, a new boswellic acid derivative and a new triterpene, respectively, from Boswellia sacra.
A new boswellic acid derivative, 11α-ethoxy-β-boswellic acid (EBA; 1) and a new ursane-type triterpene, named nizwanone (2), were isolated from Omani frankincense Boswellia sacra Flueck. together with two known compounds papyriogenin B and rigidenol. The structures of 1 and 2 were elucidated by detailed spectroscopic analysis using (1) H- and (13) C-NMR, (1) H,(1) H-COSY, HMQC, HMBC, and HR-EI-MS techniques. The relative configurations of 1 and 2 were assigned by comparative analysis of the NMR spectral data with those of known analogs together with NOESY experiments. Structures of known compounds were identified by comparison with the reported data.
Chem Biodivers. 2013 Aug;10(8):1501-6.
Chemistry and biology of essential oils of genus boswellia.
The properties of Boswellia plants have been exploited for millennia in the traditional medicines of Africa, China, and especially in the Indian Ayurveda. In Western countries, the advent of synthetic drugs has obscured the pharmaceutical use of Boswellia, until it was reported that an ethanolic extract exerts anti-inflammatory and antiarthritic effects. Frankincense was commonly used for medicinal purposes. This paper aims to provide an overview of current knowledge of the volatile constituents of frankincense, with explicit consideration concerning the diverse Boswellia species. Altogether, more than 340 volatiles in Boswellia have been reported in the literature. In particular, a broad diversity has been found in the qualitative and quantitative composition of the volatiles with respect to different varieties of Boswellia. A detailed discussion of the various biological activities of Boswellia frankincense is also presented.
Evid Based Complement Alternat Med. 2013;2013():140509.
Synthesis of an antitumor active endoperoxide from 11-keto-beta-boswellic acid.
An endoperoxide was synthesized starting from 11-keto-beta-boswellic acid and screened for antitumor activity in a panel of 15 human cancer cell lines by an SRB assay. The compound induces apoptosis and shows an average IC(50) value of 0.4-4.5 microM.
Eur J Med Chem. 2010 Sep;45(9):3840-3.
Comparative study of the chemical composition and antioxidant activity of six essential oils and their components.
The antioxidant activities and the determined major components of six popular and commercially available herb essential oils, including lavender (Lavendular angustifolia), peppermint (Mentha piperita), rosemary (Rosmarius officinalis), lemon (Citrus limon), grapefruit (Citrus paradise), and frankincense (Boswellia carteri), were compared. The essential oils were analysed by GC-MS and their antioxidant activities were determined by testing free radical-scavenging capacity and lipid peroxidation in the linoleic acid system. The major components of the essential oils of lavender, peppermint, rosemary, lemon, grapefruit, and frankincense were linalyl acetate (28.2%), menthol (33.4%), 1,8-cineole (46.1%), limonene (64.5 and 94.2%), and p-menth-2-en-ol (34.5%), respectively. The highest DPPH radical-scavenging activity was obtained by the lavender essential oil and limonene, with RC50 values of 2.1 +/- 0.23% and 2.1 +/- 0.04%, respectively. Radical-scavenging activity against the ABTS radical was highest in peppermint essential oil (1.6 +/- 0.09). Lavender oil was most effective for inhibiting linoleic acid peroxidation after 10 days.
Nat Prod Res. 2010;24(2):140-51.
Absolute stereostructures of olibanumols A, B, C, H, I, and J from olibanum, gum-resin of Boswellia carterii, and inhibitors of nitric oxide production in lipopolysaccharide-activated mouse peritoneal macrophages.
Three new monoterpenes, olibanumols A (1), B (2), and C (3), and three new triterpenes, olibanumols H (4), I (5), and J (6), were isolated from olibanum, the exuded gum-resin from Boswellia carterii BIRDW. Their structures including the absolute configuration were determined by chemical and physicochemical evidence. Among the constituents, olibanumols A (1), H (4), and I (5), and isofouquierol (12) exhibited nitric oxide production inhibitory activity in lipopolysaccharide-activated mouse peritoneal macrophages.
Chem Pharm Bull (Tokyo). 2009 Sep;57(9):957-64.
Chemical modifications of natural triterpenes - glycyrrhetinic and boswellic acids: evaluation of their biological activity.
Synthetic analogues of naturally occurring triterpenoids; glycyrrhetinic acid, arjunolic acid and boswellic acids, by modification of A-ring with a cyano- and enone- functionalities, have been reported. A novel method of synthesis of α-cyanoenones from isoxazoles is reported. Bio-assays using primary mouse macrophages and tumor cell lines indicate potent anti-inflammatory and cytotoxic activities associated with cyanoenones of boswellic acid and glycyrrhetinic acid.
Tetrahedron. 2008 Dec;64(51):11541-11548.
Cytotoxic and apoptotic activities of novel amino analogues of boswellic acids.
4-Amino analogues prepared from beta-boswellic acid and 11-keto-beta-boswellic acid, wherein the carboxyl group in ursane nucleus was replaced by an amino function via Curtius reaction, displayed improved cytotoxicity than the parent molecules. The same molecules also exhibited apoptotic activity by inducing DNA fragmentation.
Bioorg Med Chem Lett. 2007 Dec;17(23):6411-6.
Chemistry and immunomodulatory activity of frankincense oil.
The yield of steam distillation of frankincense essential oil (3%); and its physicochemical constants were determined. Capillary GC/MS technique was used for the analysis of the oil. Several oil components were identified based upon comparison of their mass spectral data with those of reference compounds published in literature or stored in a computer library. The oil was found to contain monoterpenes (13.1%), sesquiterpenes (1%), and diterpenes (42.5%). The major components of the oil were duva-3,9,13-trien-1,5alpha-diol-1-acetate (21.4%), octyl acetate (13.4%), o-methyl anisole (7.6%), naphthalene decahydro-1,1,4a-trimethyl-6-methylene-5-(3-methyl-2-pentenyl) (5.7%), thunbergol (4.1%), phenanthrene-7-ethenyl-1,2,3,4,4a,5,6,7,8,9,10,10a-dodecahydro-1,1,4a,7-tetramethyl (4.1%), alpha-pinene (3.1%), sclarene (2.9%), 9-cis-retinal (2.8%), octyl formate (1.4%), verticiol (1.2%) decyl acetate (1.2%), n-octanol (1.1%). The chemical profile of the oil is considered as a chemotaxonomical marker that confirmed the botanical and geographical source of the resin. Biologically, the oil exhibited a strong immunostimulant activity (90% lymphocyte transformation) when assessed by a lymphocyte proliferation assay.
Z Naturforsch C J Biosci. 2003;58(3-4):230-8.
3-Acetoxy group of genuine AKBA (acetyl-11-keto-beta-boswellic acid) is alpha-configurated.
The pentacyclic triterpenoid 3-acetyl-11-keto-beta-boswellic acid (AKBA) from the resin of Boswellia spec. is a potent inhibitor of 5-lipoxygenase (5-LO). We noticed discrepancies in the nomenclature and stereochemistry of the 3-acetoxy group of boswellic acids. Isolation of AKBA under mild conditions and the data from the first X-ray crystallography study evidence the 3 alpha-orientation of AKBA's acetoxy function.
Planta Med. 2000 Dec;66(8):781-2.
J Org Chem. 2000 Sep;65(19):6278-82.
Workup-dependent formation of 5-lipoxygenase inhibitory boswellic acid analogues.
Pentacyclic triterpenes from the 11-keto-boswellic acid series were identified as the active principal ingredients of Boswellia resin, inhibiting the key enzyme of leukotriene biosynthesis, 5-lipoxygenase (5-LO). Of the genuine boswellic acids hitherto characterized, 3-O-acetyl-11-keto-beta-boswellic acid, AKBA (1), proved to be the most potent inhibitor of 5-LO. In the course of purification of further boswellic acid derivatives from Boswellia resin, we observed the degradation of the natural compound 3-O-acetyl-11-hydroxy-beta-boswellic acid (2) to the thermodynamically more stable product 3-O-acetyl-9, 11-dehydro-beta-boswellic acid (4). The metastable intermediate of this conversion, under moderate conditions of workup in methanolic solutions, was identified as 3-O-acetyl-11-methoxy-beta-boswellic acid (3). The novel artifactual boswellic acid derivatives inhibited 5-LO product formation in intact cells with different characteristics: 4 almost totally abolished 5-LO activity, with an IC(50) of 0.75 microM, whereas 3 and 9,11-dehydro-beta-boswellic acid (5), the deacetylated analogue of 4, were incomplete inhibitors. The data suggest that the conditions chosen for the workup of Boswellia extracts could significantly influence the potency of their biological actions and their potential therapeutic effectiveness.
J Nat Prod. 2000 Aug;63(8):1058-61.
Structure-activity relationships of the nonredox-type non-competitive leukotriene biosynthesis inhibitor acetyl-11-keto-β-boswellic acid.
Acetyl-11-keto-β-boswellic acid (AKBA) from Boswellia serrata Roxb. and italics Boswellia carterii Birdw. is the first selective, direct, non-competitive and non-redox-type inhibitor of 5-lipoxygenase, the key enzyme for leukotriene biosynthesis (Safayhi et al., 1992). Previously, we showed that AKBA interacts with the 5-lipoxygenase via a pentacyclic triterpene selective effector site (Safayhi et al., 1995). In order to study the impact of AKBA's functional groups on enzyme inhibition, natural and synthetic analogues of this boswellic acid were tested for 5-lipoxygenase inhibition in intact rat neutrophils (Sailer et al., 1996 a). The results reveal that the carboxylic group of AKBA combined with the 11-keto-group is essential for enzyme inhibition, whereas the acetoxy-group on position C-3 α increases the affinity of AKBA to its effector site. Furthermore, other experiments demonstrated that minor structural modifications could cause a total loss of binding affinity and/or inhibitory activity of these compounds.
Phytomedicine. 1996 May;3(1):73-4.
Isolation and structure of a 4-O-methyl-glucuronoarabinogalactan from Boswellia serrata.
Carbohydr Res. 1992 Jan;223():321-7.
CHEMICAL STANDARDIZATION OF 'KUNDUR' (Oleo-Gum-Resin of Boswellia serrata Roxb).
A comparative study of the original and market samples of the KUNDUR (Oleo-Gum-Resin of Boswellia serrata Roxb.) with special reference to its chemical standardization and the qualitative and quantitative studies have been discussed here.
Anc Sci Life. 1984 Jul;4(1):48-50.