Effect of triterpenes and triterpene saponins from the stem bark of Kalopanax pictus on the transactivational activities of three PPAR subtypes.

Kalopanax pictus (Araliaceae) is a deciduous tree that grows in East Asian countries. Its stem bark and leaves have been used in traditional medicine to treat rheumatic arthritis, neurotic pain, and diabetes mellitus. A phytochemical study on a methanol extract of the stem bark of K. pictus resulted in the isolation of three new compounds, 6β,16α-dihydroxy-hederagenin 3-O-β-D-glucuronopyranoside (1), 3-O-β-D-glucuronopyranosyl-28-O-β-D-glucopyranosyl-6β,16α-dihydroxy-oleanolic acid (2), and 3-O-β-D-galactopyranosyl(1→3)-α-L-arabinopyranosyl hederagenin 28-O-β-D-glucopyranosyl-(1→6)-β-D-glucopyranosyl ester (3), along with eight known compounds (4-11). Their structures were established on the basis of chemical and spectroscopic methods (IR, 1D and 2D NMR, and HRESITOFMS). Compounds 1-6 and 8-10 upregulated PPARs transcriptional activity in a dose-dependent manner in HepG2 cells, with EC(50) values in the range 0.20-15.5 μM. Moreover, the specific PPAR transactivational effects of compounds 1-6 and 8-10 on separate PPAR subtypes, PPARα, -γ, and -β(δ) were further investigated. Compounds 4, 5, 8, and 10 showed significant PPARα transactivational activity, with EC(50) values of 7.8, 8.0, 10.3, and 17.3 μM, respectively. Compounds 2, 4, 6, and 8-10 exhibited PPARγ dose-dependent transactivational activity, with EC(50) values of 14.7, 15.5, 14.8, 10.9, 17.1, and 16.3 μM, whereas compounds 8 and 10 significantly upregulated PPARβ(δ) transcriptional activity, with EC(50) values of 15.7 and 17.7 μM, respectively.