Inhibitory effects of beta-boswellic acids on 12-O-tetradecanoylphorbol-13-acetate-induced inflammation, expression of pro-inflammatory cytokines, arachidonic acid metabolism, and tumor promotion in mouse skin

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Boswellia serrata extracts have been used for centuries as an herbal medicine for the treatment of inflammation and related diseases in India and China. A preparation of Boswellia extract (BE) contains about 35-40% total beta-boswellic acids and further separated and purified by a Phenomenex Synergi MAX-RP 80A column into 6 peaks. Four peaks were identified as beta-boswellic acid, 3-O-acetyl-beta-boswelic acid, 11-keto-beta-boswellic acid and 3-O-acety-11-keto-beta-boswellic acid, respectively. The other 2 peaks were alpha-boswellic acid and 3-O-acetyl-alpha-boswellic acid. Beta-boswellic acid and its 3 derivatives had strong anti-inflammatory activity in mouse ear edema test. Topical application of TPA (0.8 nmol) onto ears of CD-1 mice once a day for 4-5 days induced persistent inflammation that was corrected with elevated protein levels of pro-inflammatory cytokines as well as formation of PGE2 and LTB4 levels in the mouse ears. Topical application of BE and pure beta-boswellic acid at 30 min before each TPA application once a day for 4 days inhibited TPA-induced persistent inflammation and expression IL-1beta and IL-6 protein levels as well as inhibited formation of LTB4 levels, but not PGE2 levels in mouse ears. Oral administration of 3.5 and 14 mg of 3-O-acetyl-11-keto-beta-boswellic acid in corn oil to the female CD-1 mouse at 30 min before TPA treatment inhibited TPA-induced ear edema by 53% and 64%, respectively. Beta-boswellic acid appears to have advantage with high systemic bioavailability in comparison to other anti-inflammatory and anti-tumor agent such as curcumin. Topical application of 1.2 and 3.6 mg of BE before TPA (5 nmol) to skin of DMBA-initiated mice twice a week for 16 weeks inhibited the average number of skin tumors per mouse by 87 and 99%, respectively, and the percent of the mice with skin tumors was decreased by 59 or 92%, respectively. The results indicating that BE and beta-boswellic acids had strong anti-inflammatory and cancer preventive activities.