Dammarane-type triterpenoid saponins isolated from Gynostemma pentaphyllum ameliorate liver fibrosis via agonizing PP2Cα and inhibiting deposition of extracellular matrix / 中国天然药物

Gypenosides, structurally analogous to ginsenosides and derived from a sustainable source, are recognized as the principal active compounds found in Gynostemma pentaphyllum, a Chinese medicinal plant used in the treatment of the metabolic syndrome. By bioactive tracking isolation of the plants collected from different regions across China, we obtained four new gypenosides (1-4), together with nine known gypenosides (5-13), from the methanol extract of the plant. The structures of new gypenosides were elucidated by one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) spectra, complemented by chemical degradation experiments. Through comprehensive evaluation involving COL1A1 promoter assays and PP2Cα activity assays, we established a definitive structure-activity relationship for these dammarane-type triterpenoids, affirming the indispensability of the C-3 saccharide chain and C-17 lactone ring in effectively impeding extracellular matrix (ECM) deposition within hepatic stellate cells. Further in vivo study on the CCl4-induced liver damage mouse model corroborated that compound 5 significantly ameliorated the process of hepatic fibrosis by oral administration. These results underscore the potential of dammarane-type triterpenoids as prospective anti-fibrotic leads and highlight their prevalence as key molecular frameworks in the therapeutic intervention of chronic hepatic disorders.

Identification of Dammarane-type Triterpenoid Saponins from the Root of Panax ginseng

The root of Panax ginseng, is a Korea traditional medicine, which is used in both raw and processed forms due to their different pharmacological activities. As part of a continued chemical investigation of ginseng, the focus of this research is on the isolation and identification of compounds from Panax ginseng root by open column chromatography, medium pressure liquid chromatography, semi-preparative-high performance liquid chromatography, Fast atom bombardment mass spectrometric, and nuclear magnetic resonance. Dammarane-type triterpenoid saponins were isolated from Panax ginseng root by open column chromatography, medium pressure liquid chromatography, and semi-preparative-high performance liquid chromatography. Their structures were identified as protopanaxadiol ginsenosides [gypenoside-V (1), ginsenosides-Rb1 (2), -Rb2 (3), -Rb3 (4), -Rc (5), and -Rd (6)], protopanaxatriol ginsenosides [20(S)-notoginsenoside-R2 (7), notoginsenoside-Rt (8), 20(S)-O-glucoginsenoside-Rf (9), 6-O-[alpha-L-rhamnopyranosyl(1-->2)-beta-D-glucopyranosyl]-20-O-beta-D-glucopyranosyl-3beta,12beta, 20(S)-dihydroxy-dammar-25-en-24-one (10), majoroside-F6 (11), pseudoginsenoside-Rt3 (12), ginsenosides-Re (13), -Re5 (14), -Rf (15), -Rg1 (16), -Rg2 (17), and -Rh1 (18), and vinaginsenoside-R15 (19)], and oleanene ginsenosides [calenduloside-B (20) and ginsenoside-Ro (21)] through the interpretation of spectroscopic analysis. The configuration of the sugar linkages in each saponin was established on the basic of chemical and spectroscopic data. Among them, compounds 1, 8, 10, 11, 12, 19, and 20 were isolated for the first time from P. ginseng root.