Research Highlights
2000 - 2003
on Boswellin from 2000 to 2003

Immunomodulatory activity of boswellic acids of Boswellia sata Roxb
Pungle P, Banavalikar M, Suthar A, Biyani M, Mengi S
Indian J Exp Biol. 2003 Dec; 41(12); 1460-1462

The present study analysed the extract of gum resin of B. serrata [BA] containing 60% acetyl 11-keto beta boswellic acid along with other constituents such as 11-keto beta-boswellic acid, acetyl beta-boswellic acid and beta-boswellic acid for anti-anaphylactic and mast cell stabilizing activity. Results suggest that BA extract showed promising anti-anaphylactic and mast cell stabilizing activity.

Immunomodulatory triterpenoids from the oleogum resin of Boswellia carterii Birdwood
Badria FA, Mikhaeil BR, Maatooq GT, Amer MM
Z Naturforsch [C] 2003 Jul-Aug; 58(7-8); 505-516

The authors studied the immunomodulatory bioassay-guided fractionation of the oleogum resin of frankincense (Boswellia carterii Birdwood) resulted in the isolation and identification of 9 compounds; palmitic acid and eight triterpenoids belonging to lupane, ursane, oleanane, and tirucallane skeleta were isolated form the resin. The lymphocyte transformation assay of the isolated compounds proved that the total extract retained more activity.

A lupane triterpene from frankincense (Boswellia sp., Burseraceae)
Culioli G, Mathe C, Archier P, Vieillescazes C
Phytochemistry 2003 Feb; 62(4); 537-541

Authors in this study explored a new lupane-type triterpene, 3alpha-hydroxy-lup-20(29)-en-24-oic acid, isolated from the methanolic extract of "Erytrean-type" resin of commercial frankincense together with the known 3 alpha-hydroxy-olean-12-en-24-oic acid and 3alpha-hydroxy-urs-12-en-24-oic acid. Their structures were characterized on the basis of chemical and spectral evidence including two dNMR experiments and mass spectrometric techniques.

Boswellic acid acetate induces differentiation and apoptosis in highly metastatic melanoma and fibrosarcoma cells.
Zhao W, Entschladen F, Liu H, Niggemann B, Fang Q, Zaenker KS, Han R
Cancer Detect Prev 2003; 27(1); 67-75

The aim of this study was to investigate the antitumor and/or preventive effect of BC-4, an isomeric compound isolated from the plant Boswellia carteri Birdw containing alpha- and beta-boswellic acid acetate inhibited the secretion of MMPs from HT-1080 cells. In conclusion, BC-4 is a good candidate for the prevention of primary tumor, invasion and metastasis.

Boswellic acids trigger apoptosis via a pathway dependent on caspase-8 activation but independent on Fas/Fas ligand interaction in colon cancer HT-29 cells
Liu JJ, Nilsson A, Oredsson S, Badmaev V, Zhao WZ, Duan RD
Carcinogenesis 2002 Dec; 23(12); 2087-2093

Authors in this study analysed Boswellic acids for its anti-inflammatory properties. They studied their antiproliferative and apoptotic effects on colon cancer cells and the pathway leading to apoptosis. HT-29 cells were treated with beta-boswellic acid (BA), keto-beta-boswellic acid (K-BA) and acetyl-keto-beta-boswellic acid (AK-BA), respectively. The apoptosis induced by AK-BA was inhibited completely by caspase-3 or caspase-8 inhibitor. In conclusion, boswellic acids, particularly AK-BA and K-BA have antiproliferative and apoptotic effects.

Keto- and acetyl-keto-boswellic acids inhibit proliferation and induce apoptosis in Hep G2 cells via a caspase-8 dependent pathway
Liu JJ, Nilsson A, Oredsson S, Badmaev V, Duan RD
Int J Mol Med. 2002 Oct; 10(4); 501-505

In this study authors investigated the apoptotic and anti-proliferative effects of two types of boswellic acids, keto-beta-boswellic acid and acetyl-keto-beta-boswellic acid on liver cancer Hep G2 cells. After treating the cells with the boswellic acids, cell proliferation, DNA synthesis and apoptosis were analysed. Boswellic acids strongly induced apoptosis accompanied by activation of caspase 3, 8 and 9. In conclusion, boswellic acids have anti-proliferation and anti-cancer effects on Hep G2 cells.

Cytostatic and apoptosis-inducing activity of boswellic acids toward malignant cell lines in vitro
Hostanska K, Daum G, Saller R
Anticancer Res 2002 Sep-Oct; 22(5); 2853-2862

In the present study authors analysed role of Boswellic acids derived from frankincense. Because of the relevance for the clinical application, they tested the boswellic acids for its cytotoxic, cytostatic and apoptotic activity on five leukemia (HL-60, K 562, U937, MOLT-4, THP-1) and two brain tumor cell lines. The Boswellia serrata extract induced dose-dependent antiproliferative effects. The results of this study suggest the effectiveness of Boswellia serrata extract with defined content of boswellic acids.

Chemical components of Boswellia carterii
Zhou JY, Cui R
Yao Xue Xue Bao 2002 Aug; 37(8); 633-635

The aim of this study was to investigate the chemical components of Boswellia carterii. Results show six compounds were isolated and their structures were identified as acetyl-alpha-boswellic acid (1), acetyl-beta boswellic acid (2), lup-20-ene-3 alpha-acetoxy-24-oic acid (3), alpha-boswellic acid (4), beta-boswellic acid (5) and acetyl-11-keto-beta-boswellic acid (6). Compound 3 is a new constituent.

Determination of 11-keto-boswellic acid in human plasma
Kaunzinger A, Baumeister A, Cuda K, Häring N, Schug B, Blume HH, Raddatz K, Fischer G, Schubert-Zsilavecz M
J Pharm Biomed Anal 2002 May 15; 28(3-4); 729-739

The study explores a sensitive, specific, accurate, fast and reproducible GC/MS-method for the quantitative determination of 11-keto-boswellic acid in human plasma using 18 alpha-glycyrrhetinic acid as the internal standard. The precision and accuracy for quality control and standards is better than 15%. The recovery of the extraction method is calculated as 84%. The assay was applied successfully to determine plasma level of 11-keto boswellic acid in a clinical pilot study.

Cytotoxic action of acetyl-11-keto-beta-boswellic acid (AKBA) on meningioma cells
Park YS, Lee JH, Bondar J, Harwalkar JA, Safayhi H, Golubic M
Planta Med. 2002 May; 68(5); 397-401

This study focuses on Acetyl-11-keto-beta-boswellic acid (AKBA) is a naturally occurring pentacyclic triterpene isolated from gum resin exudate of the tree Boswellia serrata. Because pentacyclic triterpenes have antiproliferative and cytotoxic effects against different tumor types, we investigated whether AKBA would act in a similar fashion on primary human meningioma cell cultures. The cytotoxic action of AKBA on meningioma cells may be mediated by inhibition of Erk signal transduction pathway.

Boswellic acids activate p42(MAPK) and p38 MAPK and stimulate Ca(2+) mobilization
Altmann A, Fischer L, Schubert-Zsilavecz M, Steinhilber D, Werz O
Biochem Biophys Res Commun 2002 Jan 11; 290(1); 185-190

Here authors show that extracts of Boswellia serrata gum resins and its constituents, the boswellic acids (BAs) activate the mitogen-activated protein kinases, p42(MAPK) and p38 in isolated human polymorphonuclear leukocytes. MAPK activation was rapid and transient with maximal activation after 1-2.5 min of exposure and occurred in a dose-dependent manner. Our results suggest that 11-keto-BAs might function as potent activators of PMNL by stimulation of MAPK and mobilization of intracellular Calcium.

Acetyl-11-keto-beta-boswellic acid (AKBA) is cytotoxic for meningioma cells and inhibits phosphorylation of extracellular-signal regulated kinase 1 and 2
Park YS, Lee JH, Harwalkar JA, Bondar J, Safayhi H, Golubic M
Adv Exp Med Biol 2002; 507; 387-393

Present study focused on Acetyl-11-keto-beta-boswellic acid (AKBA) a naturally occurring pentacyclic triterpene isolated from gum resin exudate from stem of the tree Boswellia serrata. Authors investigated effects of AKBA on the proliferation of 11 primary cell cultures established from human surgical specimens of meningiomas, central nervous system tumors. Treatment of meningioma cells by AKBA revealed potent cytotoxic activity with half-maximal inhibitory concentrations in the range 2-8 microM.

Boswellic acid as the active principle in the treatment of chronic inflammatory diseases
Ammon HP
Wien Med Wochenschr 2002; 152(15-16); 373-388

This study focused on the preparations from gum resin of Boswellia serrata for the treatment of inflammatory diseases. Boswellic acids inhibit leukotriene biosynthesis in neutrophilic granulocytes by a non-redox, noncompetitive inhibition of 5 lipoxygenase. Moreover certain boswellic acids have been described to inhibit elastase in leukocytes, to inhibit proliferation induced apoptosis. In clinical trials promising results were observed in patients with rheumatoid arthritis, chronic colitis, ulcerative colitis, Crohn's disease, bronchial asthma and peritumoral brains edemas.

Effects of gum resin of Boswellia serrata in patients with chronic colitis
Gupta I, Parihar A, Malhotra P, Gupta S, Lüdtke R, Safayhi H, Ammon HP
Planta Med 2001 Jul; 67(5); 391-395

Authors in the present study used gum resin of Boswellia serrata for the treatment of chronic colitis. Thirty patients, 17 males and 13 females in the age range of 18 to 48 years with chronic colitis were in this study. Twenty patients were given a preparation of Boswellia serrata (900 mg daily divided in three doses for 6 weeks) and ten patients were given sulfasalazine (3 gm daily divided in three doses for 6 weeks) served as controls. Out of 20 patients treated with Boswellia gum resin 14 went into remission while sulfasalazine remission rate was 4 out of 10. In conclusion this study shows that a gum resin from Boswellia serrata could be effective in chronic colitis.

Acetyl-11-keto-beta-boswellic acid, a constituent of a herbal medicine from Boswellia serrata resin attenuates experimental ileitis
Krieglstein CF, Anthoni C, Rijcken EJ, Laukötter M, Spiegel HU, Boden SE, Schweizer S, Safayhi H, Senninger N, Schürmann G
Int J Colorectal Dis 2001 Apr; 16(2); 88-95

In this study authors examined the effect of Boswellia extract and its single constituent acetyl-11-keto-beta-boswellic acid (AKBA) on leukocyte-endothelial cell interactions in an experimental model of IBD. Ileitis was induced by two subcutaneous injections of indomethacin (7.5 mg/kg) in Sprague-Dawley rats 24 h apart. Oral therapy with Boswellia extract or AKBA significantly reduces macroscopic and microcirculatory inflammatory features indicating that anti-inflammatory actions in IBD may be due to boswellic acids such as AKBA.

Boswellic acid, a potent antiinflammatory drug, inhibits rejection to the same extent as high dose steroids
Dahmen U, Gu YL, Dirsch O, Fan LM, Li J, Shen K, Broelsch CE
Transplant Proc 2001 Feb-Mar; 33(1-2); 539-541

Therapy of active Crohn disease with Boswellia serrata extract H15
Gerhardt H, Seifert F, Buvari P, Vogelsang H, Repges R
Z Gastroenterol 2001 Jan; 39(1); 11-17

The purpose of this clinical trial was to compare efficacy and safety of Boswellia serrata extract H15 with mesalazine for the treatment of active Crohn's disease. Randomised, double-blind, parallel group comparison for which 102 patients were selected. Population included 44 patients treated with H15 and 39 patients treated with mesalazine. Primary outcome measures the change of Crohn Disease Activity Index (CDAI) between the status at the time of enrolment and at the end of therapy, to conclude that therapy with H15 is not inferior to mesalazine. Considering both safety and efficacy of Boswellia serrata extract H15 it appears to be superior over mesalazine.

Boswellic acids in the palliative therapy of children with progressive or relapsed brain tumors
Janssen G, Bode U, Breu H, Dohrn B, Engelbrecht V, Göbel U
Klin Padiatr 2000 Jul-Aug; 212(4); 189-195

This clinical study reports the findings in which 19 children and adolescents with intracranial tumors received a palliative therapy with H15 at a maximum dose of 126 mg/kg of BW/day. All had previously been treated with conventional therapy. 5/19 children reported an improvement of their general health status. 3/17 patients with malignant tumors showed a mainly transient improvement of neurological symptom such as pareses and ataxia. An antiproliferative effect cannot be stated.

Acetyl-boswellic acids are novel catalytic inhibitors of human topoisomerases I and II alpha
Syrovets T, Büchele B, Gedig E, Slupsky JR, Simmet T
Mol Pharmacol 2000 Jul; 58(1); 71-81

The authors in this study used Acetyl-boswellic acids (acetyl-BA) a pentacyclic triterpenes derived from gum resin of frankincense. They have now investigated the mechanism of action of acetyl-BA. Data demonstrate that acetyl-BA and some other pentacyclic triterpenes, such as betulinic acid, ursolic acid and oleanolic acid inhibit topoisomerases I and II alpha through a mechanism that does not involve stabilization of the cleavable complex or the intercalation of DNA. Thus acetyl-BA are a unique class of dual catalytic inhibitors of human topoisomerases I and II alpha.

Topical formulation of a new plant extract complex with refirming properties. Clinical and non-invasive evaluation in a double-blind trial
Martelli L, Berardesca E, Martelli M
Int J Cosmet Sci 2000 Jun; 22(3); 201-206

In the present study authors have investigated the OTC formulation versus placebo in a double-blind trial to evaluate its ability to improve elasticity and firmness of the skin. The clinical non-invasive evaluation in 20 volunteers shows: 1]. No adverse reactions such as itching or irritation. 2]. Efficacy and cosmetic acceptibility of the test cream. 3]. An increase in electrical capacitance (moisture content) even though without statistical significance. This result is not surprising because the patients had healthy skin and were relatively young. 4]. A significant improvement in the biomechanical properties (extensibility and firmness) of the skin. Main components of the cream (boswellic acids, Sylibin and Centella asiatica extracts) were formulated as complexes with lyso-phospholipids and soya bean non-saponifiable lipids.

Anti-tumor and anti-carcinogenic activities of triterpenoid, beta-boswellic acid
Huang MT, Badmaev V, Ding Y, Liu Y, Xie JG, Ho CT
Biofactors 2000; 13(1-4); 225-230

The present study deals with the use of Boswellin (BE) for the treatment of inflammatory and arthritic diseases. Topical application of BE to the backs of mice markedly inhibited 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced increases in skin inflammation, epidermal proliferation, the number of epidermal cell layers and tumor promotion in 7, 12-dimethylbenz[a]anthracene (DMBA)-initiated mice. Addition of beta-boswellic acid, 3-O-acetyl-beta boswellic acid, 11-keto-beta-boswellic acid or 3-O-acetyl-11-keto-beta-boswellic acid to human leukemia HL-60 cell culture inhibited DNA synthesis. These results indicate that beta boswellic acid have anti-carcinogenic, anti-tumor and anti-hyper lipidemic activities.

Boswellic acids inhibit glioma growth: a new treatment option?
Winking M, Sarikaya S, Rahmanian A, Jödicke A, Böker DK
J Neurooncol 2000; 46(2); 97-103

The present study evaluated use of Boswellic acid for malignant glioma therapy. In an earlier study authors showed a significant reduction on perifocal edema by gum resin extract for malignant glioma. The purpose was to elucidate the effects of boswellic acids on tumor growth in vivo. Female wistar rats weighing 200-250 g were treated with drug 14 days after inoculation of C6 tumor. Results conclude that the proportion of apoptotic tumor cells in animals with high dose treatment was significantly larger than in low dose.

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