Research Highlights from 2009 to 2010

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

Yoshikawa M, Morikawa T, Oominami H, Matsuda H
Chem Pharm Bull (Tokyo). 2009 Sep;57(9):957-64

The present study isolated three new monoterpenes, olibanumols A, B, and C, and three new triterpenes, olibanumols H, I, and J from Olibanum, the exuded gum resin from Boswellia carterii Birdw. Their structures and configuration were determined by chemical and physicochemical evidence. Among the constituents, olibanumols A, H, and I, and isofouquierol exhibited nitric oxide production inhibitory activity in lipopolysaccharide-activated mouse peritoneal macrophages.


Identification of human cathepsin G as a functional target of boswellic acids from the anti-inflammatory remedy frankincense

Tausch L, Henkel A, Siemoneit U, Poeckel D, Kather N, Franke L, Hofmann B, Schneider G, Angioni C, Geisslinger G, Skarke C, Holtmeier W, Beckhaus T, Karas M, Jauch J, Werz O J Immunol. 2009 Sep 1;183(5):3433-42

This study reported the evidence for the anti-inflammatory effects of Frankincense. Boswellic acids (BAs) constitute major pharmacological principles of frankincense, but their targets and modes of action are still unclear. Using a BA-affinity Sepharose matrix, a 26-kDa protein was isolated from human neutrophils and identified it as the lysosomal protease cathepsin G (catG). In molecular docking experiments, BAs tightly bound to the active centreofcatG. BAs suppressed the proteolytic activity of catGwith an IC50value of approximately 600 nM in a competitive and reversible manner. BAs inhibited chemoinvasion but not chemotaxis of challenged neutrophils. In conclusion, catG was found to be a functional and pharmacologically relevant target of BAs and this could explain some of the anti-inflammatory properties of frankincense.


In vivo genotoxicity evaluation of a plant based antiarthritic and anticancer therapeutic agent Boswelic acids in rodents

Sharma R, Singh S, Singh GD, Khajuria A, Sidiq T, Singh SK, Chashoo G, Pagoch SS, Kaul A, Saxena AK, Johri RK, Taneja SC Phytomedicine. 2009 Dec;16(12):1112-8

The present study was carried out in Wistar rats using different cytogenetic assay system-abnormalities viz. chromosomal aberrations; sperm morphology, micronuclei and comet assays. Animals received boswellic acids (BA) at a dose of 125, 250, 500 and 1000mg/kg P.O., prepared as 2% gum acacia suspension. The results revealed that BA was quite safe as it did not show any genotoxicity at any dose level up to 1000mg/kg.



LY294002 enhances boswellic acid-induced apoptosis in colon cancer cells

Liu JJ, Duan RD Anticancer Res. 2009 Aug;29(8):2987-91

The present study had investigated whether the apoptotic effects of boswellic acid could be affected by inhibition of the PI3K/Akt pathway. Colon cancer HT29 cells were treated with 3-acetyl-11-keto-β boswellic acid [AKBBA] in the absence and presence of LY294002 or Wortmanin, inhibitors of PI3K. Results revealed that AKBBA at 30 microM only slightly induced apoptosis. Preincubation of the cells with LY294002 or wortmannin significantly enhanced the AKBBA-induced apoptosis up to 20-fold. Further study showed that at the doses used, AKBBA induced phosphorylation of Akt at both Ser473 and Thr308 positions, indicating an activation of the PI3K/Akt pathway. Together it concluded that AKBBA may activate the PI3K/Akt pathway and inhibition of the PI3K pathway significantly enhances AKBBA-induced apoptosis.


Acetyl-11-keto-β-boswellic acid inhibits prostate tumor growth by suppressing vascular endothelial growth factor receptor 2-mediated angiogenesis

Pang X, Yi Z, Zhang X, Sung B, Qu W, Lian X, Aggarwal BB, Liu M Cancer Res. 2009 Jul 15;69(14):5893-900

This study showed that acetyl-11-keto-β-boswellic acid (AKBBA) could strongly inhibit tumor angiogenesis. AKBBA suppressed tumor growth in the human prostate tumor xenograft mice treated daily (10 mg/kg AKBBA) after solid tumors reached approximately 100 mm. It reported that AKBBA significantly inhibited blood vessel formation in the Matrigel plug assay in mice and effectively suppressed vascular endothelial growth factor (VEGF)-induced microvessel sprouting in rat aortic ring assay ex vivo. AKBBA potently inhibits human prostate tumor growth through inhibition of angiogenesis induced by VEGFR2 signalling pathways.


Activation of p53/p21/PUMA alliance and disruption of PI-3/Akt in multimodal targeting of apoptotic signaling cascades in cervical cancer cells by a pentacyclic triterpenediol from Boswellia serrata

Bhushan S, Malik F, Kumar A, Isher HK, Kaur IP, Taneja SC, Singh J Mol Carcinog. 2009 Dec;48(12):1093-108

This study had reported that the apoptotic cell death in human cervical cancer HeLa and SiHa cells by a pentacyclic triterpenediol (TPD) from Boswellia serrata is by a mechanism different from what has been reported in HL-60 cells. TPD caused oxidative stress by the early generation of nitric oxide and reactive oxygen species that robustly up-regulated the time-dependent expression of p53/p21/PUMA while conversely abrogating phosphatidylinositol-3-kinase (PI3K)/Akt pathways in parallel. TPD also decreased the expression of PI3K/pAkt, ERK1/2, NF-kappaB/Akt signaling cascades which coordinately contribute to cancer cell survival. TPD may thus find usefulness in managing and treating cervical cancer.


Antibacterial activity of oleo-gum resins of Commiphoramolmol and Boswellia papyrifera against methicillin resistant Staphylococcus aureus (MRSA)

Abdallah EM, Khalid AS, Ibrahim N Scientific Research and Essay. 2009 April;4(4):351-6

This study investigated the antibacterial activity of the extracts from oleo-gum resins of two Arabian medicinal plants, Commiphoramolmol Engl. ex Tschirchand Boswellia papyrifera against methicillin-resistant Staphylococcus aureus (MRSA). The phytochemical investigation demonstrated that the methanol extracts exhibited the highest antibacterial activity whereas the ethyl acetate extracts exhibited some degree of activity and the petroleum ether and water extracts exhibited no or least activity. It concluded that the minimum inhibitory concentration (MIC) ranged between 31.25 and 250 μg/ml for oleo-gum resin methanol extract of C. molmol and of B. papyrifera ranged from 62.5 to 500 μg/mL, respectively.


On the interference of boswellic acids with 5-lipoxygenase: mechanistic studies In vitro and pharmacological relevance.

Siemoneit U, Pergola C, Jazzar B, Northoff H, Skarke C, Jauch J, Werz O Eur J Pharmacol. 2009 Mar 15;606(1-3):246-54

This study investigated whether 11-keto-boswellic acids interfere with 5-LO under physiologically relevant conditions (i.e., in whole blood assays) and whether they inhibit 5-LO in vivo. Inhibition of human 5-LO by the major naturally occurring boswellic acids was analyzed in cell-free and cell-based activity assays. Factors influencing 5-LO activity (i.e., Ca(2+), phospholipids, substrate concentration) significantly modulate the potency of 11-keto-boswellic acids to inhibit 5-LO. Moreover, 11-keto-boswellic acids suppressed 5-LO product formation in isolated neutrophils (IC50=2.8 to 8.8 µM) but failed to inhibit 5-LO product formation in human whole blood. In the presence of albumin (10 mg/ml), 5-LO inhibition by 11-keto-boswellic acids (up to 30 µM) in neutrophils was abolished. Finally, a single dose (800 mg) oral administration of frankincense extracts to human healthy volunteers failed to suppress leukotriene B(4) plasma levels. Their data show that boswellic acids are direct 5-LO inhibitors that efficiently suppress 5-LO product synthesis invitro test models, but the pharmacological relevance of such interference in vivo seems questionable.


Permeation of Boswellia extract in the Caco-2 model and possible interactions of its constituents KBBA and AKBBA with OATP1B3 and MRP2

Krüger P, Kanzer J, Hummel J, Fricker G, Schubert-Zsilavecz M, Abdel-Tawab M Eur J Pharm Sci. 2009 Feb 15;36(2-3):275-84

The present study provides an explanation for the pharmacokinetic properties of 11-keto-β-boswellic acid (KBBA) and 3-acetyl-11-keto-β-boswellic acid (AKBBA). The permeability in human Caco-2 cell lines revealed poor permeability of AKBBA and moderate absorption of KBBA. The interaction of KBBA and AKBBA with the organic anion transporter [OATP1B3] and multidrug-resistant proteins P-glycoprotein [MRP2] lead to the conclusion that therapeutically relevant interactions might exist between these moieties.


Interventions for treating microscopic colitis: A Cochrane Inflammatory Bowel Disease and Functional Bowel Disorders Review Group systematic review of randomized trials

Chande N, MacDonald JK, McDonald JW Am J Gastroenterol. 2009 Jan;104(1):235-41

This study conducted a systematic review to determine effective treatments for patients with collagenous colitis or lymphocytic colitis, the two subtypes of microscopic colitis. A total of 10 randomized trials included patients with collagenous colitis. It concluded that budesonide is effective and well-tolerated for inducing and maintaining clinical and histological responses in patients with collagenous colitis. The evidence for other agents including bismuth subsalicylate, prednisolone, B. serrata extract, probiotics, and mesalamine with or without cholestyramine was weaker and needs further research.


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

Tripathi YB Recent Pat Inflamm Allergy Drug Discov. 2009 Jan;3(1):49-57

This review discussed the role of BHUx, a novel polyherbal formulation consisting of 5 medicinal plants namely Termenalia arjunaStrychnoxnux vomicaBoswellia serrataCommiphoramukul, and Semecarpus anacardium, in the treatment of hyperlipidemia, inflammation, obesity, and atherosclerosis. In this paper, anti-oxidant, anti-inflammatory, hypo-lipidemic, anti-proliferative properties of BHUx were reveiwed in several experimental models based on chemical tests, cell culture, in vitro models, and in vivo experiments with normal and transgenic animals.


Boswellic acids: A group of medicinally important compounds

Shah BA, Qazi GN, Taneja SC Nat Prod Rep. 2009 Jan;26(1):72–89

This review containing over 276 references covers the progress made in the chemistry and bioactivity of this important group of triterpenoids. Though initially known for their anti-inflammatory and antiarthritic activities through a unique 5-LO inhibition mechanism, boswellic acids have recently attained significance due to their anticancer properties. The phytochemistry and chemical modifications, including mechanism of action, are discussed.


Antimicrobial and phytochemical screening of Boswellia serrata Roxb., Rhus mysorensis Heyne., Strychnos potatorum Linn.F. and Schefflera stellata Gaertn

Aman M, Rai RV, Samaga PV Med and AroPla Sci and Bio. 2010;4(1):69-72

This study evaluated the antimicrobial activity of methanolic extracts of leaves and flowers of Boswellia serrata as well as other plant species. The method used was a paper disc diffusion assay. Both leaf and flower extract showed potent antimicrobial activity against X. Oryzaepv. oryzae, X. axanopodispv. malvacaerum, Staphylococcus aureus, and S. typhi while moderate or no effect was seen against E. aerogenes, P. aeruginous, Micrococcus species, and B. cereus. The results show that Boswellia serrata could be a broad-spectrum antimicrobial for humans and animals as well as the bio-control agent for plants (as it also inhibited the plant pathogens).


Evaluation of Boswellia serrata oleo-gum resin for wound healing activity

Mallik A, Goupalea D, Dhongadeb H, Nayak S Der Pharm Lettre. 2010;2(2):457-63

The present study tested the Boswellia serrata oleo gum resin for the wound healing property. For this, a cream was formulated with 5, 10 and 15% of oleo-gum-resin. Wistar rats of either sex were randomly divided into 5 groups and incision wound was made on the dorsal side of each animal. Control group received only base without Boswellia serrata oleo gum resin whereas group 2-4 received cream with 5, 10 and 15% of oleo-gum-resin, respectively. The standard group received the application of povidone-iodine. The percentage of wound contraction and tensile strength of the healed wound in treated groups was calculated and compared with control and standard groups. The treatment groups showed a significant increase in wound contraction percentage in a dose-dependent manner, with the group receiving cream with 15% oleo-gum resin showing 98.02% improvement as against 84.37% shown by the standard. Tensile strength was similar to that of the standard. These results justify the wound healing activity of Boswellia serrata oleo-gum-resin.


Role of the methanolic extracts of Boswellia serrata and Lavandula angustifolia on apomorphine induced ejaculation in male Wistar rats

Zaringhalam J, Shams J, Rezazadeh S, Manaheji H, AkhondzadehS, Asefifar F Journal of Medicinal Plant Research. 2010;4(11):1073-80

The present study evaluated the effect of methanolic extract of Boswellia serrata and the other plant on ejaculatory responses induced by apomorphine in male Wistar rats. Boswellia serrata extract was administered at the doses of 50, 100 and 200mg/kg half an hour before the induction of ejaculation with apomorphine and the number of semen drops was counted. Compared to control and the groups treated with 50 and 200mg/kg extracts, group with 100mg/kg of Boswellia serrata extract showed a significant effect (P<0.05). In conclusion, Boswellia serrata was effective in reducing the ejaculatory effects of apomorphine and could be used effectively in rapid ejaculation.


Evaluation of Heptoprotective activity of Boswellia serrata leaves extracts in Albino rats

Zeeyauddin K, Setty RCS, Syed-Abdul MM, Ibrahim M
Indian Drugs, 2010;47(2):19-24

This study evaluated the hepatoprotective activity of Boswellia serrata leaves petroleum ether and ethanolic extract using paracetamol-induced hepatotoxicity (3 g per kg) in albino rats. The hepatoprotective activity was found to be more pronounced in petroleum ether leaf extract (250 mg /kg) of B. serrata plant as it significantly reduced the elevated levels of serum bilirubin, SGPT, SGOT and increased the levels of total proteins. Histopathological observations also confirm the hepatoprotective activity of B. serrata leaf extracts in albino rats.