Dammarane-type triterpenoid saponins isolated from Gynostemma pentaphyllum ameliorate liver fibrosis via agonizing PP2Cα and inhibiting deposition of extracellular matrix.
10.1016/S1875-5364(23)60395-4
- Author:
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
Author Information
1. Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China.
2. Helmholtz International Lab, State Key Laboratory of Microbial Technology, Shandong University, Qingdao 266237, China.
3. Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: lhhu@njucm.edu.cn.
4. Jiangsu Key Laboratory for Functional Substances of Chinese Medicine, School of Pharmacy, Nanjing University of Chinese Medicine, Nanjing 210023, China. Electronic address: yinanzhang@njucm.edu.cn.
- Publication Type:Journal Article
- Keywords:
Dammarane-type triterpenoid;
Extracellular matrix;
Gypenoside;
Liver fibrosis
- MeSH:
Animals;
Mice;
Gynostemma;
Liver Cirrhosis/drug therapy*;
Triterpenes/pharmacology*;
Ginsenosides;
Extracellular Matrix;
Dammaranes
- From:
Chinese Journal of Natural Medicines (English Ed.)
2023;21(8):599-609
- CountryChina
- 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.
