Chinese Journal of Natural Medicines (English Ed.) 2023;21(8):599-609

doi:10.1016/S1875-5364(23)60395-4

Dammarane-type triterpenoid saponins isolated from Gynostemma pentaphyllum ameliorate liver fibrosis via agonizing PP2Cα and inhibiting deposition of extracellular matrix.

Yue LIU 1 ; Yating YANG 2 ; Hanghang WANG 1 ; Han LI 1 ; Qi LV 1 ; Xiachang WANG 1 ; Dalei WU 2 ; Lihong HU 3 ; Yinan ZHANG 4

Affiliations

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Keywords

Dammarane-type triterpenoid; Extracellular matrix; Gypenoside; Liver fibrosis

Country

China

Language

English

Abstract

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.