Research Highlights from 2000 to 2003

Immunomodulatory activity of boswellic acids of Boswellia serrata Roxb

Pungle P, Banavalikar M, Suthar A, Biyani M, Mengi S
Indian J Exp Biol. 2003 Dec;41(12):1460-2

The present study analyzed the effects of oral administration of B. serrata gum resin extract containing 60% acetyl-11-keto β-boswellic acid along with other constituents such as 11-keto β-boswellic acid, acetyl β-boswellic acid and β-boswellic acid in passive paw anaphylaxis and compound 48/80-induced degranulation of mast cell methods using disodium cromoglycate (50 mg/kg, i.p.) as standard reference. The results have suggested the promising antianaphylactic and mast cell stabilizing activity of B. serrata extract.

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):505-16

The study reported the isolation of palmitic acid as well as eight triterpenoids (lupeol, β-boswellic acid, 11-keto-β-boswellic acid, acetyl β-boswellic acid, acetyl 11-keto-β-boswellic acid, acetyl-α-boswellic acid, 3-oxo-tirucallic acid, and 3-hydroxy-tirucallic acid) belonging to lupane, ursane, oleanane, and tirucallane skeletal from the oleo-gum resin of frankincense (Boswellia carterii Birdwood) using immunomodulatory bioassay-guided fractionation. The lymphocyte transformation assay of the isolated compounds proved that the total extract retained more activity than any purified compound.

A lupane triterpene from frankincense (Boswellia sp., Burseraceae)

Culioli G, Mathe C, Archier P, Vieillescazes C
Phytochemistry. 2003 Feb;62(4):537-41

This study had explored a new lupane-type triterpene, 3α-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-α-hydroxy-olean-12-en-24-oic acid and 3-α-hydroxy-urs-12-en-24-oic acid i.e., α- and β-boswellic acids, respectively. Their structures were characterized based on the chemical and spectral analysis including 2D NMR and mass spectrometry.

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

This study investigated the antitumor and/or preventive effect of BC-4, an isomeric compound isolated from the plant Boswellia carteri Birdw. containing α- and β-boswellic acid acetate using MTT assay. BC-4 inhibited topoisomerase II activity, arrested cells in the G1 phase, induced differentiation, arrested cell migration in mouse melanoma cells. It also inhibited the secretion of MMPs and induced apoptosis in fibrosarcoma cells. The study concluded saying BC-4 is a good candidate for the prevention of invasion, and metastasis and primary tumor.

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):2087-93

This study investigated the antiproliferative and apoptotic effects of boswellic acids (BA, KBBA, and AKBBA)on colon cancer cells (HT-29 cell line) and elucidated the pathway leading to apoptosis. The study concluded, boswellic acidsespeciallyKBBA and AKBBA have antiproliferative and apoptotic effects.It attributed the apoptosis to caspase-8 activation independent of Fas/FasL interaction.

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):):501-5

This study investigated the apoptotic and anti-proliferative effects of two types of boswellic acids, keto-β-boswellic acid and acetyl-keto-β-boswellic acid on liver cancer Hep G2 cells. After treating the cells with the boswellic acids, cell proliferation, DNA synthesis, apoptosis and caspase enzymes activities were assessed. Boswellic acids strongly induced apoptosis accompanied by activation of caspases 3, 8 and 9, thus it concluded boswellic acids may have a promising role in the prevention of liver cancer.

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);2853-62

The present study analyzed the cytotoxic, cytostatic and apoptotic role of standardized boswellic acids extract derived from Boswellia serrata gum resin on five leukemia cell lines (HL-60, K 562, U937, MOLT-4, THP-1) and two brain tumor cell lines(LN-18, LN-229). The standardized extract of B. serrata induced dose-dependent antiproliferative effects in all the cell lines tested. The results of the study suggested the antiproliferative effectiveness of B.serrata gum resin standardized extract in cancer cell lines.

Chemical components of Boswellia carterii

Zhou JY, Cui R Yao XueXue Bao. 2002 Aug;37(8):633-5

This study investigates the chemical components of Boswellia carterii. It reported the isolation and identification of structures of six compounds: acetyl-α-boswellic acid, acetyl-β-boswellic acid, lup-20(29)-ene-3 α-acetoxy-24-oic acid, α-boswellic acid, β-llic acid and acetyl-11-keto-β-boswellic acid. The lup-20(29)-ene-3 α-acetoxy-24-oic acid is a new constituent reported in B. carterii.

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):729-39

The study reported sensitive, specific, accurate, fast and reproducible GC/MS-method for the quantitative determination of 11-keto-boswellic acid in human plasma using 18α-glycyrrhetinic acid as an internal standard. The overall precision and accuracy for quality control and standards by this method is better than 15%. The recovery of the extraction method was calculated as 84%. The assay was applied successfully to determine the plasma concentrations of11-keto boswellic acid in a pilot clinical study.

Cytotoxic action of acetyl-11-keto-β-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 focused on acetyl-11-keto-β-boswellic acid (AKBBA), a naturally occurring pentacyclic triterpene isolated from gum resin exudate of Boswellia serrata. It investigated the antiproliferative and cytotoxicity effects on primary human meningioma cell cultures. AKBBA showed potent cytotoxic action on meningioma cells and inhibited the activation of Erk-1 and Erk-2, cell proliferation markers.

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):185-90

This study showed the activation of the mitogen-activated protein kinases (MAPK), p42 and p38 in isolated human polymorphonuclear leukocytes (PMNL) by boswellic acids (BAs). The MAPK activation by BAs was rapid, transient and dose-dependent with maximal activation 1-2.5 min after the exposure. Further, it revealed that 11-keto-BAs function as potent activators of PMNL by stimulation of MAPK and mobilization of intracellular Calcium.

Acetyl-11-keto-β-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;507:387-93

The present study focused on acetyl-11-keto-β-boswellic acid (AKBBA), a naturally occurring pentacyclic triterpene isolated from gum resin exudate from Boswellia serrata, and investigated the effects of AKBBA on the proliferation of 11 primary cell cultures established from human surgical specimens of central nervous system tumors, meningiomas. Treatment of meningioma cells by AKBBA revealed potent, rapid cytotoxic activity with half-maximal inhibitory concentrations in the range 2-8 microM by inhibiting the activation of Erk-1/2 signal transduction pathway.

Boswellic acid (components of frankincense) as the active principle in the treatment of chronic inflammatory diseases

Ammon HP Wien Med Wochenschr. 2002;152(15-16):373-8

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

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):391-5

The present study used gum resin of Boswellia serrata for the treatment of chronic colitis. Thirty patients, 17 males, and 13 females in the aged18 to 48 years were in this study. Twenty patients were given a preparation of Boswellia serrata (900 mg daily divided into three doses for 6 weeks) and ten patients were given sulfasalazine (3 gm daily divided in three doses for 6 weeks). Out of 20 patients treated with Boswellia gum resin, 14 went into remission while sulfasalazine remission rate was 4 out of 10. Also, 18 out of 20 patients showed improvement in at least one of the parameters. In conclusion, this study shows that a gum resin from Boswellia serrata could be effective in chronic colitis.

Acetyl-11-keto-β-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

This study examined the effect of Boswellia extract and its single constituent acetyl-11-keto-β-boswellic acid (AKBBA) on leukocyte-endothelial cell interactions in an experimental rat model of IBD. Ileitis was induced by subcutaneous injections of indomethacin (7.5 mg/kg) in Sprague-Dawley rats. Oral therapy with Boswellia extract or AKBBA significantly reduces macroscopic and microcirculatory inflammatory features, indicating anti-inflammatory actions are due to boswellic acids such as AKBBA.

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):539-41

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):11-7

This clinical trial compared the efficacy and safety of Boswellia serrata extract H15 with mesalazine in patients with active Crohn’s disease. Forty-four patients were supplemented with H15 and 39 were patients treated with mesalazine. The primary outcome measured was the change in Crohn’s Disease Activity Index (CDAI) status from the time of enrolment to the end of therapy, and concluded that therapy with H15 is not inferior to mesalazine. In terms of benefit-risk-evaluation, considering both safety and efficacy of Boswellia serrata extract H15 appeared 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):189-95

This clinical study reported 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. Five out of 19 children reported an improvement in their general health status. Three out of 17 patients with malignant tumors showed a mainly transient improvement of neurological symptoms such as pareses and ataxia.

Acetyl-boswellic acids are novel catalytic inhibitors of human topoisomerases I and II α

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 α 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 α.

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):201-6

This study had investigated the OTC formulation versus placebo in a double-blind clinical trial to evaluate its ability to improve the elasticity and firmness of the skin. The main components of the cream (boswellic acids, Sylibin, and Centella asiatica extracts) were formulated as complexes with lysophospholipids and soya bean non-saponifiable lipids. Non-invasive clinical evaluation in 20 volunteers had shown: no adverse reactions such as itching or irritation, efficacy and cosmetic acceptability of the test cream, and a non-significantly increased electrical capacitance (moisture content). However, these results were not surprising because the patients were relatively young and had healthy skin. Further, a significant (P<0.02) improvement in the biomechanical properties (extensibility and firmness) of the skin was observed.

Anti-tumor and anti-carcinogenic activities of triterpenoid, β-boswellic acid

Huang MT, Badmaev V, Ding Y, Liu Y, Xie JG, Ho CT
Biofactors. 2000;13(1-4):225-30

The present study deals with the use of Boswellin 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 β-boswellic acid, 3-O-acetyl-β-boswellic acid, 11-keto-β-boswellic acid or 3-O-acetyl-11-keto-β-boswellic acid to human leukemia HL-60 cell culture inhibited DNA synthesis. These results indicate that the major constituents of BE, β boswellic acid and its derivatives have anti-carcinogenic, anti-tumor, and anti-hyperlipidemic 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 the use of Boswellic acid for malignant glioma therapy. In an earlier study, authors showed a significant reduction in 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 the drug for 14 days starting immediately after the inoculation of C6 tumor cells. Results have shown significantly longer survival time (P< 0.05) and a larger proportion of apoptotic tumor cells (P< 0.05) in animals treated with higher dose levels (3 x 240 mg/kg bw) compared to lower dose treatment.