title: Differential inhibitory effects of salvianolic acids on activation of rat hepatic stellate cells by platelet-derived growth factor.
abstract: Platelet-derived growth factor (PDGF) induces cell proliferation together with oxidative stress. The present study investigated the effects of salvianolic acid A (Sal A) and B (Sal B) on the PDGF-induced signaling cascades in hepatic stellate cells (HSCs). HSC-T6, a rat hepatic stellate cell line, was stimulated with PDGF (10 ng/mL). The inhibitory effects of Sal A and B on oxidative stress-related signaling pathways were assessed in vitro. The protein levels were measured by Western blotting. FACS analysis was applied to detect the thioredoxin (Trx) level. Sal A and B showed different inhibitory abilities on the PDGF-related pathway. Sal A inhibited 70-kDa ribosomal S6 kinase (p70(s6k)) and associated proteins. Sal B attenuated PDGF-induced c-jun-N-terminal kinase (JNK), p38, and PKC- δ phosphorylations. Both Sal A and B diminished the activation of PKD, Trx, heme-oxygenase (HO)-1, and Nrf2. Taken together, our results showed that Sal A and B attenuated PDGF-induced ROS formation in HSCs, possibly through different signaling pathways.
authors.affiliation: Institute of Traditional Medicine, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Ming-Kuei
authors.initials: MK
authors.lastname: Tsai
authors.forename: Yun-Lian
authors.initials: YL
authors.lastname: Lin
authors.forename: Yi-Tsau
authors.initials: YT
authors.lastname: Huang
mesh_terms: D000818:Animals; D001572:Benzofurans / Q000494:pharmacology*; D002109:Caffeic Acids / Q000494:pharmacology*; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D055166:Hepatic Stellate Cells / Q000378:metabolism; D007773:Lactates / Q000494:pharmacology*; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000378:metabolism / Q000517:prevention & control*; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation; D018517:Plant Roots / Q000737:chemistry; D010982:Platelet-Derived Growth Factor / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism*; D027561:Salvia miltiorrhiza / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects; D053630:Depsides
chemical_list: D001572:Benzofurans; D002109:Caffeic Acids; D007773:Lactates; D010982:Platelet-Derived Growth Factor; D017382:Reactive Oxygen Species; C066201:salvianolic acid A; C076944:salvianolic acid B; D053630:Depsides