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Prevention Research 1: Modulation of Arachidonic Acid Metabolism

Abstract #749

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

Rutgers University, Piscataway, NJ, Sabinsa Inc., Piscataway, NJ, Rutgers University, New Brunswick, NJ

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.