Anti-inflammatory and antitumor-promoting effects of the triterpene acids from the leaves of Eriobotrya japonica

Sixteen triterpene acids, viz., five of the oleanane-type (1-5), nine of the ursane-type (6-14), and two of the lupane-type (15, 16), were isolated and identified from the ethyl acetate-soluble fraction of the methanol extract of the leaves of loquat, Eriobotrya japonica LINDL. (Rosaceae). Twelve of these compounds, 1-4, 6, 8-13, and 15, were evaluated for their inhibitory effects on 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation (1 mu g/ear) in mice. All the compounds tested showed a marked anti-inflammatory effect, with a 50% inhibitory dose (ID50) of 0.03-0.43 mg per ear. In addition, an evaluation against the Epstein-Barr virus early antigen (EBV-EA) activation induced by TPA for all of the compounds, 12 and 13 showed potent inhibitory effects on EBV-EA induction. Furthermore, euscaphic acid (12) exhibited marked antitumor-promoting activity in an in vivo two-stage carcinogenesis test of mouse tumor by using 7,12-dimethylbenz[a]anthracene (DMBA) as an initiator and TPA as a promoter.