Research highlights from 2007 to 2008

Inhibitory effect of acetyl-11-keto-beta-boswellic acid on androgen receptor by interference of Sp1 binding activity in prostate cancer cells

Yuan HQ, Kong F, Wang XL, Young CY, Hu XY, Lou HX
Biochem Pharmacol 2008 Jun 1; 75(11); 2112-2121

In this study, researchers investigated the use of Acetyl-11-keto-beta-boswellic acid (AKBA), a compound isolated from the gum-resin of Boswellia carterii to target Androgen Receptor [AR] signalling so as to inhibit growth of prostate cancer cells. AKBA caused G1-phase cell cycle arrest with an induction of p21. AKBA-mediated inhibition of cellular proliferation was associated with a decreased AR expression at mRNA and protein levels. The results of this study suggest that anti-AR properties ascribed to AKBA could be used as a novel therapeutic chemical.

Metabolism of boswellic acids In vitro and In vivo

Krüger P, Daneshfar R, Eckert GP, Klein J, Volmer DA, Bahr U, Müller WE, Karas M, Schubert-Zsilavecz M, Abdel-Tawab M
Drug Metab Dispos 2008 Jun; 36(6); 1135-1142

Investigators in this study have used Boswellia serrata resin dry extract for the treatment of peritumoral brain edema. Pharmacokinetic studies revealed poor bioavailability, especially of 11-keto-beta-boswellic acid (KBA) and 3-acetyl-11-keto-beta-boswellic acid (AKBA), the most potent BAs. To address the question they determined the metabolic stability of KBA and AKBA in vitro and in vivo. In vitro, KBA yielded metabolic profiles similar to those obtained in-vivo, where as no metabolites of AKBA was identified in vivo and AKBA is not deacetylated to KBA. This study indicates that efficacy of B. serrata extract may be enhanced by increasing the bioavailability of AKBA.

The gastric ulcer protective effect of boswellic acids, a leukotriene inhibitor from Boswellia serrata, in rats

Singh S, Khajuria A, Taneja SC, Khajuria RK, Singh J, Johri RK, Qazi GN
Phytomedicine 2008 Jun; 15(6-7); 408-415

The present study was conducted to evaluate the anti-ulcer efficacy of boswellic acids (BA). The activity was evaluated by following universally accepted animal models viz., pyloric ligation, ethanol-HCl, acetylsalicylic acid, indomethacin and cold restrained stress-induced ulceration in rats. Results revealed that BA possess a dose dependent antiulcer effect against different experimental models. Ulcer score was 39%, 38%, 51%, 31%, 37% and 42% respectively at 250mg/kg. From the data, authors concluded that BA inhibited ulcer production non-specifically in all experimental models.

Boswellic acids: A leukotriene inhibitor also effective through topical application in inflammatory disorders

Singh S, Khajuria A, Taneja SC, Johri RK, Singh J, Qazi GN
Phytomedicine 2008 Jun; 15(6-7); 400-407

In this study authors have used Boswellic acids (BA), a natural mixture isolated from oleo gum resin of Boswellia serrata comprised of four major pentacyclic triterpene acids: beta-boswellic acid, 3-acteyl-beta-boswellic acid, 11-keto-beta-boswellic acid and 3-acetyl-11-keto-beta-boswellic acid to test its efficacy as anti-inflammatory and in Chron’s disease. They report that anti-inflammatory activity of BA through topical applications using different acute and chronic models of inflammation. Results of the study revealed that BA when used through topical application is as effective.

Comparison of the irritation potentials of Boswellia serrata gum resin and of acetyl-11-keto-beta-boswellic acid by in vitro cytotoxicity tests on human skin-derived cell lines

Burlando B, Parodi A, Volante A, Bassi AM
Toxicol Lett. 2008 Mar 15; 177(2); 144-149

The investigators in this study have used Indian frankincense a gum resin from Boswellia serrata for testing the antinflammatory properties of boswellic acids, particularly 3-O-acetyl-11-keto-beta-boswellic acid (AKBA). They evaluated in vitro cytotoxicities of B. serrata extract and AKBA on differentiated and un differentiated keratinocytes. In vitro model compared the sensitivities of different human skin cells to B. serrata indicated that the gum resin and AKBA exert moderate to low toxicity on skin.

Acetyl-keto-beta-boswellic acid induces apoptosis through a death receptor 5-mediated pathway in prostate cancer cells

Lu M, Xia L, Hua H, Jing Y
Cancer Res. 2008 Feb 15; 68(4); 1180-1186

In this report authors explored on Acetyl-keto-beta-boswellic acid (AKBA), a triterpenoid isolated from Boswellia carterri and Boswellia serrata, which has been found to inhibit tumor cell growth and induce apoptosis. The apoptotic effects and the mechanisms of action of AKBA were studied in LNCaP and PC-3 human prostate cancer cells. AKBA induced apoptosis in both cell lines at concentrations above 10ug/mL. Results suggest that AKBA induces apoptosis in prostate cancer cells through DR5-mediated pathway.

Anti-inflammatory and anti-atherogenic effects of the NF-kappaB inhibitor acetyl-11-keto-beta-boswellic acid in LPS-challenged ApoE-/- mice

Cuaz-Pérolin C, Billiet L, Baugé E, Copin C, Scott-Algara D, Genze F, Büchele B,
Syrovets T, Simmet T, Rouis M
Arterioscler Thromb Vasc Biol. 2008 Feb; 28(2); 272-277

In this article, the authors studied the effect of acetyl-11-keto-beta-boswellic acid (AKbetaBA), a natural inhibitor of proinflammatory transcription factor NF-kappaB on the development of atherosclerotic lesions in apolipoprotein E-deficient (apoE-/-) mice. Atherosclerotic lesions were induced by weekly LPS injection in apoE-/- mice. LPS alone increased atherosclerotic lesion size by approximately 100%, and treatment with AKbetaBA significantly reduced it by approximately 50%. They conclude that inhibition of NF-kappaB activity might present a new treatment strategy for atherosclerosis.

Identification and functional analysis of cyclooxygenase-1 as a molecular target of boswellic acids

Siemoneit U, Hofmann B, Kather N, Lamkemeyer T, Madlung J, Franke L, Schneider G, Jauch J, Poeckel D, Werz O
Biochem Pharmacol. 2008 Jan 15; 75(2); 503-513

Authors in the present study analysed Boswellic acids (BAs) for its anti-inflammatory principles. Initially, it was found that BAs inhibit leukotriene biosynthesis and 5-lipoxygenase. They demonstrated that BAs also interfere with platelet-type 12-lipoxygenase. Here, they show that Bas, preferably 3-O-acetyl-11-keto-beta-BA (AKBA), inhibit COX-1 product formation in intact human platelets (IC(50)=6 microM) and the activity of isolated COX-1 enzyme (IC(50) =32 microM). In conclusion, AKBA directly interfere with COX-1 and may mediate their anti-inflammatory action.

Cytotoxic and apoptotic activities of novel amino analogues of boswellic acids

Shah BA, Kumar A, Gupta P, Sharma M, Sethi VK, Saxena AK, Singh J, Qazi GN, Taneja SC
Bioorg Med Chem Lett. 2007 Dec 1; 17(23); 6411-6416

In this study authors have checked if the 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. The results displayed improved cytotoxicity than the parent molecules and also exhibited apoptotic activity.

Incensole acetate, a novel anti-inflammatory compound isolated from Boswellia resin, inhibits nuclear factor-kappa B activation

Moussaieff A, Shohami E, Kashman Y, Fride E, Schmitz ML, Renner F, Fiebich BL, Munoz E, Ben-Neriah Y, Mechoulam R
Mol Pharmacol 2007 Dec; 72(6); 1657-1664

The authors analysed Boswellia resin for its anti-inflammatory activity using inhibitor of nuclear factor-kappaB alpha (IkappaB alpha) degradation in tumor necrosis factor (TNF) alpha-stimulated HeLa cells. They isolated two novel nuclear factor-kappaB (NF-kappaB) inhibitors from the resin, their structures elucidated as incensole acetate (IA) and its nonacetylated form, incensole. Cembrenoid diterpenoids specifically IA may thus constitute a potential novel group of NF-kappaB inhibitors

Boswellic acids: biological actions and molecular targets

Poeckel D, Werz O
Curr Med Chem 2006; 13(28); 3359-3369

The authors have screened six plant extracts and isolated compounds for anti microbial effects on bacteria and yeasts with dermatological relevance. The following plant extracts have been tested: Gentiana lutea, Harpagophytum procumbens, Boswellia serrata, Usnea barbata, Rosmarinus officinalis and Salvia officinalis. Additionally, the following compounds were tested: usnic acid, carnosol, carnosic acid, ursolic acid, oleanolic acid, harpagoside, boswellic acid and gentiopicroside. The extracted compounds were tested against 29 aerobic and anaerobic bacteria. It is concluded that anti microbial effects of plant extracts may be used for treatment of acne vulgaris and seborrhoic eczema.

Boswellic acids and glucosamine show synergistic effect in preclinical anti-inflammatory study in rats

Singh S, Khajuria A, Taneja SC, Khajuria RK, Singh J, Qazi GN
Bioorg Med Chem Lett. 2007 Jul 1; 17(13); 3706-3711

Authors in the present study revealed the synergistic effect of boswellic acid mixture (BA) and glucosamine for anti-inflammatory and anti-arthritic activities in rats. Five groups of animals were included in each of the study: the vehicle control, positive control, boswellic acids (250 mg/kg), glucosamine (250 mg/kg) and a combination of boswellic acids (125 mg/kg) and glucosamine (125 mg/kg). The combination of boswellic acids and glucosamine did result in significant anti-arthritic activity. In conclusion, a synergistic effect was observed in chronic inflammatory conditions when two chemical entities were administered in combination in this preclinical study.

Natural products as a gold mine for arthritis treatment

Khanna D, Sethi G, Ahn KS, Pandey MK, Kunnumakkara AB, Sung B, Aggarwal A, Aggarwal BB
Curr Opin Pharmacol 2007 Jun; 7(3); 344-3451

In this study investigators reviewed the role of natural products. Arthritis, a disease encompassing the inflammation of joints, results from the dysregulation of pro-inflammatory cytokines and enzymes. Numerous plant derivatives can suppress cell signaling intermediates, including curcumin (from turmeric), resveratrol (red grapes, cranberries and peanuts), tea polyphenols, genistein (soy), quercetin (onions), silymarin (artichoke), guggulsterone (guggul), boswellic acid (salai guggul) and withanolides (ashwagandha). Preclinical and clinical studies suggest that these agents have potential for arthritis treatment.

Effect of acetyl 11-keto beta-boswellic acid on metastatic growth factor responsible for angiogenesis

Singh SK, Bhusari S, Singh R, Saxena A, Mondhe D, Qazi GN
Vascul Pharmacol. 2007 May; 46(5); 333-337

Present study revealed the role of Basic fibroblast growth factor (bFGF), a metastatic growth factor is known to be one of the promoting factors in the tumor induced angiogenesis. Authors screened the antiangiogenic activity of acetyl 11-keto beta-boswellic acid against bFGF-induced angiogenesis. Acetyl 11-keto beta-boswellic acids (10 mg/kg/d) inhibited the Matrigel+bFGF-induced angiogenesis significantly.

Co-administration of acetyl-11-keto-beta-boswellic acid, a specific 5-lipoxy genase inhibitor, potentiates the protective effect of COX-2 inhibitors in kainic acid-induced neurotoxicity in mice

Bishnoi M, Patil CS, Kumar A, Kulkarni SK
Pharmacology 2007; 79(1); 34-41

Authors looked at the role of Kainic acid, a glutamate receptor agonist responsible for neuronal excitotoxicity and oxidative damage via different mechanisms is capable of stimulating both COX-2 and 5-LOX in the brain. Study was designed to study the effects of COX inhibitors and a 5-LOX inhibitor (acetyl-11-keto-beta-boswellic acid; AKBA) and the combination of these inhibitors on kainic acid induced excitotoxicity and oxidative and nitrosative damage in mice. The results indicated that AKBA, indomethacin, and nimesulide per se did not produce any change in the behavioural parameters.

Frankincense: systematic review

Ernst E
BMJ 2008 Dec 17, 337, a2813

The author reviewed all the published data reported so far from randomized clinical trials about the effectiveness of Boswellia serrata extracts (frankincense). All randomised clinical trials of B. serrata extract as a treatment for any human medical condition were included and studies of B serrata preparations combined with other ingredients were excluded. The Jadad score was used to evaluate the methodological quality of all included trials. Of the 47 potentially relevant studies, seven met all inclusion criteria (five placebo controlled, two with active controls). The included trials related to asthma, rheumatoid arthritis, crohn’s disease, osteoarthritis and collagenous colitis. Results of all trials indicated that B serrata extracts were clinically effective. Three studies were of good methodological quality and no serious safety issues were noted.

In vitro anti-biofilm activity of Boswellia spp. oleogum resin essential oils

Schillaci D, Arizza V, Dayton T, Camarda L, Di Stefano V
Lett. Appl. Microbiol. 2008 Nov, 47(5), 433-438

In the present study authors, set out to evaluate the anti-biofilm activity of the commercially available essential oils from two Boswellia species. The susceptibility of staphylococcal and Candida albicans biofilms was determined by methyltiazotetrazolium (MTT) staining. At concentrations ranging from 217.3 microgm/ml (25% v/v) to 6.8 microgm/ml (0.75% v/v) the essential oil of Boswellia papyrifera showed considerable activity against both Staphylococcus epidermidis DSM 3269 and Staphylococcus aureus ATCC 29213 biofilms. Boswellia sp. essential oils represent an interesting source of anti-microbial agents in the development of new strategies to prevent and treat biofilms.

Phytochemical analysis of the essential oil from botanically certified oleogum resin of Boswellia sacra (Omani Luban)

Al-Harrasi A., Al-Saidi S
Molecules. 2008 Sep 16, 13(9), 2181-2189

In the present study authors have developed a simple, rapid, reproducible reverse-phase high-performance liquid chromatographic method for the estimation of boswellic acids, the active constituents in Boswellia serrata oleo-gum resin. The chromatographic separation is performed using a mobile phase consisting of acetonitrile water adjusted to pH 4 with glacial acetic acid. The elution times are 4.30 and 7.11 min for 11-keto beta-boswellic acid (11-KBA) and 3-acetyl 11-keto beta-boswellic acid (A-11-KBA), respectively. They have successfully applied this method for the estimation of boswellic acids from the market formulations.

Comparison of the irritation potentials of Boswellia serrata gum resin and of acetyl-11-keto-boswellic acid by in-vitro cytotoxicity tests on human skin-derived cell lines

Bruno B.,Alessandro P., Andrea V., Anna M.B
Toxicology Letters 2008, 177, 144–149

Authors evaluated in vitro cytotoxicities of B. serrata gum extract [ 3-O-acetyl-11-ketoboswellic acid (AKBA) ] on differentiated and undifferentiated keratinocytes (HaCaT and NCTC 2544), and foetal dermal fibroblasts (HFFF2). In vitro model studies concluded that the different human skin cells are sensitive from low to moderate levels to B. serrata, gum resin and AKBA.

Acetyl-boswellic acids inhibit NFκB activation and TNF-α release by monocytes. Rationale for the treatment of chronic inflammatory diseases

Syrovets T., Estrada A.C., Laumonnier Y., Büchele B., Simmet T
Planta Med 2007, 73-81

In the present study, authors have used Acetyl-boswellic acids (ABA), Boswellia serrata Roxb. extracts to check for its relevance in the treatment of ulcerative colitis and rheumatoid arthritis. Tumor necrosis factor (TNF-α) is prevalent at the sites of chronic inflammation and its expression is tightly regulated by transcription factors such as NF-κB. They show that in endotoxin (LPS) activated human monocytes, ABA inhibit the TNF-α expression through inhibition of NF-κB signaling. ABA also inhibited IκB kinases (IKK), which is crucial for the activation of NF-κB. Thus, via their direct inhibitory effects on IKK, ABA exerts inhibition of NF-κB and subsequent downregulation of TNF-α expression in LPS-activated human monocytes. These findings suggest that ABA might be used in chronic inflammatory treatment.

Boswellic acids and glucosamine show synergistic effect in preclinical anti-inflammatory study in rats

Surjeet S., Anamika K., Subhash C. T., Ravi K. K., Jaswant S., and Ghulam N. Q
Bioorganic & Medicinal Chemistry Letters 2007, 17, 3706–3711

Authors revealed the synergistic effect of boswellic acid mixture (BA) and glucosamine for anti-inflammatory and anti-arthritic activities in rats. Two studies were conducted using the acute anti inflammatory model by carrageenan edema and chronic anti-arthritic model by Mycobacterium. Five groups of animals were used in each of the study; 1]. vehicle control, 2]. positive control (ibuprofen 100 mg/kg), 3]. boswellic acids (250 mg/kg), 4]. glucosamine (250 mg/kg) and 5]. combination of boswellic acids (125 mg/kg) and glucosamine (125 mg/kg). When BA was administered at 250 mg/kg in rats, carrageenan-induced paw edema and Mycobacterium-induced arthritis were significantly inhibited. In comparison to BA, when glucosamine was administered at 250 mg/kg it showed a mild effect in carrageenan induced edema and moderate inhibition of arthritis. The combination of boswellic acids and glucosamine showed a significant anti-arthritic activity. In conclusion, a synergistic effect was observed in chronic inflammatory conditions when two chemical entities were administered in combination.

Cytotoxic and apoptotic activities of novel amino analogues of boswellic acids

Bhahwal A. S., Ajay K., Pankaj G., Madhunika S., Vijay K. S., Ajit K. S., Jaswant S., Ghulam N. Q., Subhash C. T
Bioorganic & Medicinal Chemistry Letters 2007, 17, 6411–6416

In the present study investigators used the 4-Amino analogues prepared from b-boswellic acid and 11-keto-b-boswellic acid, wherein the carboxyl group in ursane nucleus was replaced by an amino function via curtius reaction, this displayed improved cytotoxicity than parent molecules. These new molecules also exhibited apoptotic activity by inducing DNA fragmentation.

Phytochemical Profile of Boswellia serrata: An overview

Sharma A., Mann A.S., Gajbhiye V., Kharya M.D
Pharmacognosy Reviews 2007, 1, 137-142

In this review, authors explored the phytochemical profile of the oleo-gum-resin from Boswellia serrata. Its essential oil is a mixture of mono-, di- and sesqui- terpenes revealed presence of 33 essential components. The gum fraction is composed of arabinose, xylose and galactose sugar. Resin is comprised of pentacyclic triterpenic acids such as boswellic acid, 3-O-acetyl-‘-boswellic acid, 11-keto-‘-boswellic acid and 3-O-acetyl-11-keto-‘ boswellic acid. Therapeutically it possess anti-inflammatory, anti-arthritic, anti-rheumatic, anti-diarrhoeal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, anti-microbial, analgesic, hepatoprotective and immunomodulatory activity. Boswellic acids are novel, specific, non-redox inhibitors of 5-lipoxygenase. The anti-phlogistic activity of boswellic acids is related to its anti-elastase activity.