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

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 EC50 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 EC50 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 EC50 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 EC50 values of 15.7 and 17.7 μM, respectively.