Pentacyclic Triterpenoid Saponins, Poterinasides A-J, from Silverweed Cinquefoil Roots Promising Hepatoprotective and Anti-inflammatory Agents.

Silverweed cinquefoil roots, as dietary supplements, foods, and medicines, are widely used in western areas of China, specifically in Tibet Autonomous Region and Gansu and Qinghai Provinces. In this paper, 10 new natural pentacyclic triterpenoid saponins (1-10), named poterinasides A-J, along with 14 known compounds (11-24) were isolated and purified from silverweed cinquefoil roots. The chemical structures of 1-10 were established by extensive analysis of 1D and 2D NMR data and mass spectrometric data. Poterinasides A (1), B (2), and G (7) with the unique position of substituents on the E ring had never been discovered in natural products before. Saponins 1-8, 14, and 22 displayed potent hepatoprotective activities, and 1-8, 10, 11, 14, 16, 19, and 22-24 showed outstanding anti-inflammatory effects. On the basis of the present results, some structure-activity relationships were summarized, in which 3α-OH, 19β-CH3, 20α-CH3, 20β-CH3, 21α-OH, and 30-OH groups in isolated pentacyclic triterpenoid saponins were found to strengthen the hepatoprotective and anti-inflammatory activities, respectively. Further, the following pharmacophore-based virtual screening and docking studies on special targets proteins, SIRT1 and COX-2, revealed roughly similar results with the structure-activity relationships, and this combination method was used for the first time for active natural compound screening.