Research Highlights
2009 - 2010
on Boswellin 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), 957-964.

In the present study, the authors have isolated three new monoterpenes, olibanumols A (1), B (2), and C (3), and three new triterpenes, olibanumols H (4), I (5), and J (6), from Olibanum, the exuded gum-resin from Boswellia carterii. Their structures and configuration were determined by chemical and physico- chemical evidence. Among the constituents, olibanumols A (1), H (4), and I (5), 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, 183(5), 3433-3442.
Authors in this study provide evidence for the anti-inflammatory effectiveness 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, authors isolated a 26-kDa protein from human neutrophils and identified it as the lysosomal protease cathepsin G (catG) by mass spectrometry (MALDI-TOF). In molecular docking experiments BAs tightly bound to the active center of catG. BAs suppressed the proteolytic activity of catG (IC(50) of approximately 600 nM) in a competitive and reversible manner. BAs inhibited chemoinvasion but not chemotaxis of challenged neutrophils. In conclusion, catG is a functional and pharmacologically relevant target of Bas and this could explain for 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 Aug 12
The present study was conducted to provide an explanation for the genotoxic potential of Boswelic acids (BA). Although reports on genotoxicity of Boswellia serrata dry extract and modified 3-O-acetyl-11-keto-beta-boswelic acid are available, these studies were conducted in in-vitro systems. The present study was carried out in Wistar rats using different cytogenetic assay system-abnormalities viz. chromosomal aberrations; sperm morphology, micronuclei and comet assays. Groups received BA at 125, 250, 500 and 1000mg/kg p.o., prepared as 2% gum acacia suspension. The results revealed that BA is quite safe as it did not show any genotoxicity at any dose level up to 1000mg/kg.

Aboriginal uses and management of ethnobotanical species in deciduous forests
of Chhattisgarh state in India.

Kala CP.
J Ethnobiol Ethnomed. 2009 Aug 4, 5: 20
In this paper, the author looked for the aboriginal uses of ethnobotanical species in the south Surguja district of Chhattisgarh state, India with the objective of identifying different food and medicinal plant species. Through questionnaire and personal interviews, a total of 73 ethnobotanical species used by tribal and non-tribal communities were documented, of these 36 species were used in curing different types of diseases and 22 were used as edible food plants. The destructive harvesting practices have damaged the existing populations of many ethnobotanical species viz., Asparagus racemosus, Dioscorea bulbifera, Boswellia serrata, Buchnania lanzan, Sterculia urens and Anogeissus latifolia.

LY294002 enhances boswellic acid-induced apoptosis in colon cancer cells.
Liu JJ, Duan RD.
Anticancer Res. 2009 Aug, 29(8), 2987-2991
Here the authors have investigated to see if Boswellic acids, can induce apoptosis in colon cancer cells. The phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt) pathway is crucial for cell proliferation and survival. They examined whether the apoptotic effects of boswellic acid could be affected by inhibition of PI3K/Akt pathway. Colon cancer HT29 cells were treated with 3-acetyl-11-keto-beta boswellic acid [AKBA] in the absence and presence of LY294002 or Wortmanin, inhibitors of PI3K. Results revealed that AKBA at 30 microM only slightly induced apoptosis. Preincubation of the cells with LY294002 or wortmannin significantly enhanced the AKBA-induced apoptosis up to 20-fold. Further study showed that at the doses used, AKBA induced phosphorylation of Akt at both Ser473 and Thr308 positions, indicating an activation of the PI3K/Akt pathway. In conclusion, AKBA may activate the PI3K/Akt pathway and inhibition of the PI3K pathway significantly enhances AKBA-induced apoptosis.

Acetyl-11-keto-beta-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), 5893-5900.
In this study, authors have shown that acetyl-11-keto-beta-boswellic acid (AKBA), strongly inhibit tumor angiogenesis. AKBA suppressed tumor growth in the human prostate tumor xenograft mice treated daily (10 mg/kg AKBA) after solid tumors reached approximately 100 mm. They found that AKBA 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. AKBA potently inhibits human prostate tumor growth through inhibition of angiogenesis induced by VEGFR2 signaling 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 Jun, 18 DOI 10.1002 /mc.20559
Here authors have 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 early generation of nitric oxide and reactive oxygen species that robustly up regulated 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 Commiphora molmol and Boswellia papyrifera against methicillin resistant Staphylococcus aureus (MRSA)
Emad M. Abdallah, Amna S. Khalid and Nazlina Ibrahim.
Scientific Research and Essay 2009 April, 4 (4), 351-356.
In this study authors investigated the antibacterial activity of the extracts from oleo-gum resins of two Arabian medicinal plants, Commiphora molmol Engl. ex Tschirch and Boswellia papyriferaagainst 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. They 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.

Stilbene glycosides are natural product inhibitors of FGF-2-induced angiogenesis.
Hussain S, Slevin M, Ahmed N, West D, Choudhary MI, Naz H, Gaffney J.
BMC Cell Biol. 2009 Apr, 23, 10, 30.
This paper, deals with Angiogenesis, the growth of new blood vessels from the pre-existing vasculature. This is associated with tumour development. They investigated the anti-angiogenic potential of two naturally occurring stilbene glycosides (compounds 1 and 2) isolated from the medicinal plant Boswellia papyriferai using large and smallvessel-derived endothelial cells. In conclusion , Compound 1 inhibited FGF-2 induced angiogenesis by binding to its cognate receptors and is an addition to the small number of natural product inhibitors of angiogenesis, while Compound 2 was an ineffective inhibitor of angiogenesis

Studies of the in vitro anticancer, antimicrobial and antioxidant potentials of
selected Yemeni medicinal plants from the island Soqotra.
Mothana RA, Lindequist U, Gruenert R, Bednarski PJ.
BMC Complement Altern Med. 2009 Mar, 25, 9, 7.
Recent years have witnessed a revival of interest in drug discovery from medicinal plants. The aim of the authors work was to investigate 26 plants belonging to 17 families collected from a unique place in Yemen (Soqotra Island) for their in-vitro anticancer, antimicrobial and antioxidant activities. They selected 26 plants and extracted them with methanol and hot water to yield 52 extracts. The greatest antimicrobial activity was exhibited by extracts from Acacia pennivenia, Boswellia dioscorides, Boswellia socotrana, Commiphora ornifolia, Euclea divinorum, Euphorbia socotrana, Leucas samhaensis, Leucas virgata, Rhus thyrsiflora, and Teucrium sokotranum The results show that medicinal plants can be promising sources of natural products with potential anticancer, antimicrobial and antioxidative activity.

In vitro screening for the tumoricidal properties of international medicinal herbs
Mazzio E.A., Soliman K.F
Phytother Res. 2009 Mar 23(3), 385-398

There is a growing interest in the use of anticancer complementary and alternative medicines (CAMs) worldwide. The purpose was to assess the use of a sizeable variety of diverse natural and plant sources as potential source for developing new chemotherapy drugs. In this study, 374 natural extracts (10 microg/mL-5 mg/mL) were evaluated for dose-dependent tumoricidal effects using immortal neuroblastoma of spontaneous malignant origin. The data demonstrate that most potent plant extracts were randomly dispersed within the plantae kingdom (LC (50) = 31-490 microgm/mL) in the order of the lowest to the highest LC(50) Dioscorea villosa (Dioscoreaceae) > Sanguinaria canadensis (Papaveraceae) > Dipsacus asper (Dipsacaceae) > Populus balsamifera (Salicaceae) > Boswellia carteri (Burseraceae) > Cyamopsis psoralioides (Fabaceae) > Rhamnus cathartica (Rhamnaceae) > Larrea tridentate (Zygophyllaceae) > Dichroa febrifuga (Hydrangeaceae) > Batschia canescens (Boraginaceae) > Kochia scoparia (Chenopodiaceae) > Solanum xanthocarpum (Solanaceae) > Opoponax chironium (Umbelliferae) > Caulophyllum thalictroides (Berberidaceae) > Dryopteris crassirhizoma (Dryopteridaceae) > Garcinia cambogia (Clusiaceae) > Vitex agnus-castus (Verbenaceae) >Calamus draco (Arecaceae).

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), 246-254.
In this study, authors 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 (IC(50)=2.8 to 8.8 muM) 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 muM) in neutrophils was abolished. Finally, 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 in in vitro 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 KBA and AKBA 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), 275-284

The present study provides an explanation for pharmacokinetic properties of KBA and AKBA. Boswellia serrata extract was used in the treatment of inflammatory diseases. Pharmacokinetic studies yielded low plasma concentrations of the active ingredients 11-keto-beta-boswellic acid (KBA) and 3-acetyl-11-keto-beta-boswellic acid (AKBA). The permeability in human Caco-2 cell lines revealed poor permeability of AKBA and moderate absorption of KBA. The interaction of KBA and AKBA with the organic anion transporter [OATP1B3] and multi drug 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), 235-241.
In this study authors 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. Bismuth subsalicylate, prednisolone, and mesalamine with or without cholestyramine may be effective, whereas Boswellia serrata extract and probiotics were ineffective for treating collagenous colitis. To conclude 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 is weaker and needs further research.

Boswellic acid blocks signal transducers and activators of transcription 3 signaling, proliferation and survival of multiple myeloma via the protein tyrosine phosphatase SHP-1
Kunnumakkara A.B., Nair A.S., Sung B., Pandey M.K., Aggarwal B.B
Mol Cancer Res. 2009 Jan, 7(1), 118-128

Authors investigated the role of acetyl-11-keto-beta-boswellic acid (AKBA), derived from Boswellia serrata in the activation of signal transducers and activators of transcription-3 (STAT-3) and its relevance in survival, proliferation & chemoresistance of human multiple myeloma (MM). Agents that can suppress STAT3 activation have potential as cancer therapeutics. The results show that AKBA inhibited constitutive STAT3 activation in MM cells. They concluded that AKBA is a novel inhibitor of STAT3 and has potential in cancer treatment.

BHUx: a patented polyherbal formulation to prevent hyperlipidemia and atherosclerosis
Tripathi Y.B
Recent Pat Inflamm Allergy Drug Discov. 2009, 3(1), 49-57

In this review, the author discusses the role of BHUx, a novel polyherbal formulation, consisting of 5 medicinal plants namely Termenalia arjuna, Strychnoxnux vomica, Boswellia serrata, Commiphora mukul 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 have been studied on 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 B.A., Qazi G.N., Taneja S.C
Nat. Prod. Rep. 2009, 26, 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 anti-cancer properties. The phytochemistry and chemical modifications, including mechanism of action, are discussed.

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