Boswellia serrata has been traditionally used in India and other countries since ancient times for the treatment of several diseases including inflammatory disorders and cancer with minimum side effects. The active constituents of the extract, namely, boswellic acids were shown to inhibit 5-lipoxygenase and human leukocyte elastase and were shown to be direct, non-redox inhibitors of mammalian 5-lipoxygenase. In experimental animal models, boswellic acids have been shown to be beneficial in Crohn's disease, ulcerative colitis and ileitis. Boswellia extract also showed inhibitory action on topoisomerase I and II, in vitro. The extract also induced caspase activation-dependent apoptosis in various cancer cell lines. AKBAmax™ was approximately 3 times more effective than camptothecin, a drug normally prescribed in colorectal cancer cases that are refractory to standard chemotherapy treatment. Boswellic acids were reported to increase intracellular calcium and activity of mitogen activated protein kinase (MAPK) in human isolated leukocytes.

Boswellic acids are a mixture of 6 components of which AKBA (3-O-acetyl-11-keto- boswellic acid) is a minor component, constituting only 2-3% of the total boswellic acids. However, AKBAmax™ has the highest pharmacological effect among the various boswellic acids, as shown below.

1 Antiproliferative and apoptic effects on colon cancer cells - beta boswellic acid (BA), 11-keto-boswellic acid (KBA) and 3-O-acetyl-11-keto-boswellic acid (AKBA) were tested for their relative efficacies. Both KBA and AKBA were active, AKBA being more active. [Liu, J.J. et al, Carcinogenesis, 2002, 23(12), 2087-93; Int. J. Mol. Med., 2002, 10(4), 501-5]

2 Activation of mitogen-activated protein kinases in isolated human polymorphonuclear leukocytes - Both KBA and AKBA produced substantial activation; boswellic acids lacking the 11-keto groups were ineffective [Altman, A., et al, Biochem. Biophys. Res. Commun., 2002, 290(1), 185-90].

3 Of the four boswellic acids, AKBA proved to be the most potent inhibitor of 5-lipoxygenase (5-LO). [Schweizer, S. et al., J. Nat. Prod., 2000, 63(8), 1058-61].

4 Mixed acetyl boswellic acids significantly inhibited ionophore-stimulated release of leukotrienes B4 and C4 from intact human polymorphonuclear neutrophil leukocytes. Purified AKBA was about 3 times more potent [Wildfeuer, A., et al, Arzneimittelforschung, 1998, 48(6), 668-74].

5 Inhibitory activity of boswellic acids against human leukemia HL-60 cells in culture – among the 4 boswellic acids, AKBA produced the most pronounced effect. [Shao, Y., et al, Planta Med., 1998, 64(4), 328-31]

6 Among the boswellic acids, AKBA induced the most pronounced inhibition of 5-LO [Safayhi, H., et al, J. Pharamcol. Exp. Ther., 1992, 261(3), 1143-46; Sailer E.R. et al, Br. J. Pharmacol., 1996, 117(4), 615-8; Sailer et al, Eur. J. Biochem., 1998, 256, 364-68]

7 Ammon et al (EP 0552657) lists the anti-inflammatory activities of 6 boswellic acids in the order of their biological activity based on IC50 values: AKBA, beta-BA, KBA, alpha-BA , ABA, AABA.

8 AKBA decreased the activity of human leukocyte elastase (HLE) in vitro the most [Safayhi, H. et al, Planta Med., 1997, 63, 487-93]

9 Treatment of lymphoproliferative and autoimmune disease conditions in animals including humans- AKBA was found to be the most active [Majeed, M. et al, can. Pat., CA2372772 (2001); WO00/66111]