Chem. Pharm. Bull. 54(5) 735—739 (2006)

to Japan (Japanese name, Megusurino-ki) and its stem bark has been used as a folk medicine for the treatment of hepatic disorders and eye disease. The MeOH extract of its stem bark was reported to have hepatoprotective effects and ( )rhododendrol (11) was isolated as the active principle. The stem bark is reported to contain various diarylheptanoids and phenolic compounds, and some principal diarylheptanoid constituents have been reported to exhibit inhibitory effects on the release of b-hexosaminidase in RBL-2H3 cells and on the nitric oxide production in lipopolysaccharide-activated macrophages. In the course of our search for potential antitumor promoters from natural sources, we were especially interested to undertake the investigation of A. nikoense. In this paper, we present the isolation and structure elucidation of a new diarylheptanoid of the cyclic biphenyl ether type, 1, along with nine known diarylheptanoids, 2—10, and two known phenolic compounds, 11 and 12, from a MeOH extract of its stem bark, as well as their inhibitory effects on 12O-tetradecanoylphorbol-13-acetate (TPA)-induced inflammation in mice, and on Epstein–Barr virus early antigen (EBVEA) activation induced by TPA, as primary screenings for anti-tumor promoters. The n-hexane and MeOH extracts of A. nikoense stem bark and the EtOAc-, n-BuOH-, and H2O-soluble fractions obtained from the MeOH extract were examined against TPA (1.7 nmol)-induced inflammation in mice and TPA (32 pmol)-induced EBV-EA activation in Raji cells. As shown in Table 1, the EtOAc-soluble fraction exhibited the most potent inhibitory activities in both assay systems [66% inhibition of inflammation in mice at a dose of 1.0 mg/ear; and 48.5% inhibition of TPA (32 pmol)-induced EBV-EA activation at a dose of 10 mg/ml]. The EtOAc-soluble fraction was further investigated for the active constituents in this study. Chromatography of this fraction on normal-phase and reversed-phase silica gel column and reversed-phase preparaMay 2006 735