Research highlights from 2007 to 2008

Inhibitory effect of acetyl-11-keto-β-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):2112-21

This study investigated the use of Acetyl-11-keto-β-boswellic acid (AKBBA), a compound isolated from the gum resin of Boswellia carterii to target Androgen Receptor [AR] signaling to inhibit the growth of prostate cancer cells. AKBBA caused G1-phase cell cycle arrest with an induction of p21. AKBBA-mediated inhibition of cellular proliferation was associated with a decreased AR expression at mRNA and protein levels. This study ascribed the anti-AR properties ofAKBBAtobe used as a novel therapeutic chemical.

Metabolism of boswellic acids in vitro and in vitro

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):1135-42

With the known poor pharmacokineticsofpotent boswellic acids, 11-keto-β-boswellic acid (KBBA) and 3-acetyl-11-keto-β-boswellic acid (AKBBA), the present study determined the metabolic stability of KBBA and AKBBA in vitro and compared them to pharmacokinetic profile in rats in vitro. in vitro, KBBA yielded metabolic profiles similar to those obtained in vitro, whereas no metabolites of AKBBA were identified in vitro. At the same time, AKBBA was not deacetylated to KBBA.

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):408-15

The present study evaluated the antiulcer 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 had revealed that BA possesses a dose-dependent antiulcer effect against different experimental models. Ulcer inhibition score was 39%, 38%, 51%, 31%, 37% and 42% respectively at 250mg/kg against the tested ulcer-inducing agents. From the data, the study concluded that BA inhibited ulcer production non-specifically in all the 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):400-7

The present study reported the anti-inflammatory activity of boswellic acids (BA) through topical applications using different acute and chronic models of inflammation viz. arachidonic acid and croton oil-induced mouse ear edema and carrageenan-induced rats paw edema and adjuvant-induced developing arthritis in rats. Results of the study had revealed that BA when used through topical application, is as effective as the systemic route.

Comparison of the irritation potentials of Boswellia serrata gum resin and of acetyl-11-keto-β-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):144-9

This study had evaluated the in vitro cytotoxicities of Boswellia serrata extract and 3-O-acetyl-11-keto-β-boswellic acid (AKBBA) on differentiated and undifferentiated keratinocytes (HaCaT and NCTC 2544) as well as fetal dermal fibroblasts (HFFF2). in vitro model compared the sensitivities of different human skin cells to B. serrata indicated that the gum resin and AKBBA exert moderate to low toxicity on skin.

Acetyl-keto-β-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):1180-6

This study reported the apoptotic effects and the mechanisms of action of Acetyl-keto-β-boswellic acid (AKBBA) in LNCaP and PC-3 human prostate cancer cells. AKBBA induced apoptosis in both the cell lines at concentrations above 10 µg/mL. Results suggested that AKBBA induces apoptosis in prostate cancer cells through a death receptor, DR5-mediated pathway.

Anti-inflammatory and anti-atherogenic effects of the NF-kappaB inhibitor acetyl-11-keto-β-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):272-7

This study investigated the effect of acetyl-11-keto-β-boswellic acid (AKBBA), a natural inhibitor of proinflammatory transcription factor NFKB in 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 AKBBA significantly reduced it by approximately 50% and it reduced the NFKB activity. This study concluded that the inhibition of NFKB 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;1575(2):503-13

The present study showed that BAs, preferably 3-O-acetyl-11-keto-β-BA (AKBBA), inhibit COX-1 product formation in intact human platelets (with an IC50 value of 6 µM) and the activity of isolated COX-1 enzyme (with an IC50 value of32 µM). It concluded that AKBBA directly interferes with COX-1 and may mediate the anti-inflammatory action besides the suppression of lipoxygenases.

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 117(23):6411-6

This study had reported that the 4-amino analogs prepared from β-boswellic acid and 11-keto-β-boswellic acid, wherein the carboxyl group in the ursane nucleus was replaced by an amino function via Curtius reaction, displayed improved cytotoxicity than the parent molecules, and exhibited apoptotic activity via DNA fragmentation.

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):1657-64

This study analyzed Boswellia resin for its anti-inflammatory activity using the inhibitor of nuclear factor-kappaB α (IKB) degradation in tumor necrosis factor (TNF) α-stimulated HeLa cells. Upon the isolation of two novel nuclear factor-kappaB (NFKB) inhibitors from the Boswellia resin, their structures were elucidated as incensole acetate (IA) and its nonacetylated form. IA inhibited the activation of NFKB and had a robust anti-inflammatory effect in the mice paw edema model. Cembrenoid diterpenoids specifically IA may thus constitute a potential novel group of NFKB inhibitors

Boswellic acids: biological actions and molecular targets

Poeckel D, Werz O Curr
Med Chem. 200613(28):3359-69

This is a review on gum resin extracts of Boswellia species that have been traditionally applied in folk medicine for centuries to treat various chronic inflammatory diseases, and experimental data from animal models and studies with human subjects confirmed the potential of Boswellia extracts for the treatment of not only inflammation but also of cancer. Analysis of the ingredients of these extracts revealed that the pentacyclic triterpenes boswellic acids (BAs) possess biological activities and appear to be responsible for the respective pharmacological actions. Studies elucidating the molecular mechanisms underlying the biological effects of BAs identified 5-lipoxygenase, human leukocyte elastase, topoisomerase I and II, as well as IKB kinases as molecular targets of boswellic acids. Moreover, it was shown that depending on the cell type and the structure of the boswellic acids, the compounds differentially interfere with signal transduction pathways including Ca (2+/-) and MAPK signaling in various blood cells, related to functional cellular processes important for inflammatory reactions and tumor growth.

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 117(13):3706-11

The present study revealed the synergistic effect of boswellic acid mixture (BA) and glucosamine for anti-inflammatory (by carrageenan-induced edema) and anti-arthritic activities (by Mycobacterium-induced developing arthritis) in rats. Five groups of animals were included in each of the studies: 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 a significant anti-arthritic activity. However, a synergistic effect was observed in chronic inflammatory conditions when two boswellic acids and glucosamine were administered in combination.

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):344-51

This study reviewed the role of natural products in the treatment of 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 the potential for arthritis treatment.

Effect of acetyl 11-keto β-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):333-7

The present study explored the antiangiogenic activity of acetyl 11-keto β-boswellic acid against basic fibroblast growth factor(bFGF)-induced angiogenesis. Acetyl 11-keto β-boswellic acid (10 mg/kg/d) inhibited the Matrigel+bFGF-induced angiogenesis significantly.

Co-administration of acetyl-11-keto-β-boswellic acid, a specific 5-lipoxygenase 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

The present study investigated 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. The present study investigated the effects of COX inhibitors and a 5-LOX inhibitor (acetyl-11-keto-β-boswellic acid; AKBBA) and the combination of these inhibitors on kainic acid-induced excitotoxicity and oxidative and nitrosative damage in mice. The results indicated that AKBBA, indomethacin, and nimesulide excluding rofecoxib per se did not produce any change in the behavioral parameters. However, the combination with AKBBA, rofecoxib, and nimesulide produced a more pronounced effect.

Frankincense: systematic review

Ernst E BMJ. 2008 Dec 17;337:a2813

This report is a review of all the published evidence from randomized clinical trials about the effectiveness of Boswellia serrata extracts (frankincense). All randomized 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 were 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. Together these results are encouraging but not compelling.

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):433-8

The present study evaluated 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. The essential oil of Boswellia papyrifera showed anti-biofilm activity against Staphylococcus epidermidis DSM 3269, Staphylococcus aureus ATCC 29213 and Staphylococcus epidermis RP62A biofilms. While Boswellia rivae essential oil was very active against C. albicansATCC 10231 biofilms. Finally, this study concluded statingthatBoswellia spp. 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):2181-9

The present study had developed a GC/MS technique for the estimation of essential oils from Boswellia serrata oleogum resin. Several oil components were identified based upon the comparison of their mass spectral data with those of reference compounds. The oil was characterized by the high content of the monoterpenes (97.3%) in which E-β-ocimene and limonene were the major constituents. The remaining 2.7% was accounted for the sesquiterpenes; in which the E-caryophyllene was the major constituent. Furthermore, this analysis proved the complete absence of diterpenes.

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

Burlando B, Parodi A, Volante A,
Bassi AM Toxicol Lett. 2008 Mar 15;177 (2):144–9

This study evaluated the in vitro cytotoxicities of B. serrata gum extract and especially 3-O-acetyl-11-keto-β-boswellic acid (AKBBA) on differentiated and undifferentiated keratinocytes (HaCaT and NCTC 2544), and fetal dermal fibroblasts (HFFF2). This in vitro evaluation concluded that gum resin and AKBBA of B. serrata exerts moderate to low toxicity on the skin.

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

Syrovets T, Estrada AC, Laumonnier Y, Büchele B, Simmet T
Planta Med. 2007;73(09):73-81

The present study used acetyl-boswellic acids (ABA), Boswellia serrataRoxb. extracts to check for its relevance in the treatment of ulcerative colitis and rheumatoid arthritis. Tumour 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, ABBA inhibits the TNF-α expression through inhibition of NF-κBsignalling. ABBA also inhibited IκB kinases (IKK), which is crucial for the activation of NF-κB. Thus, via their direct inhibitory effects on IKK, ABBA exerts inhibition of NF-κB and subsequent down-regulation of TNF-α expression in LPS-activated human monocytes. These findings suggest that ABBA 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 CT, Ravi KK, Jaswant S, Ghulam NQ
Bioorg Med ChemLett.2007 Jul 1;17(13):3706–11

The present study revealed the synergistic effect of boswellic acid mixture (BA) and glucosamine for anti-inflammatory (by carrageenan-induced edema) and anti-arthritic activities (by Mycobacterium-induced developing arthritis) in rats. Five groups of animals were included in each of the studies: 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 a significant anti-arthritic activity. However, a synergistic effect was observed in chronic inflammatory conditions when two boswellic acids and glucosamine were administered in combination.

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, TanejaSC Bioorg Med Chem Lett. 2007 Dec 1;17(23):6411-6

This study had reported that the 4-amino analogs prepared from β-boswellic acid and 11-keto-β-boswellic acid, wherein the carboxyl group in the ursane nucleus was replaced by an amino function via Curtius reaction, displayed improved cytotoxicity than the parent molecules and also exhibited apoptotic activity via DNA fragmentation.

Phytochemical Profile of Boswellia serrata: An overview

Sharma A, Mann AS, Gajbhiye V, Kharya MD
Pharmacognosy Reviews. 2007;1(1):137-42

This article reviewed the phytochemical profile of the oleo-gum resin from Boswellia serrata. Its essential oil is a mixture of mono-, di- and sesquiterpenes revealed the 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 possesses anti-inflammatory, anti-arthritic, anti-rheumatic, anti-diarrhoeal, anti-hyperlipidemic, anti-asthmatic, anti-cancer, anti-microbial, analgesic, hepatoprotective and immunomodulatory activities. 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.