El-Lakkany N.M.El-Maadawy W.H.Seif el-Din S.H.Saleh S.Safar M.M.Ezzat, Shahira MMohamed S.H.Botros S.S.Demerdash Z.Hammam O.A.Department of PharmacologyTheodor Bilharz Research InstituteWarak El-HadarImbaba P.O. Box 30Giza12411Egypt; Department of Pharmacology and ToxicologyFaculty of PharmacyCairo UniversityCairo11562Egypt; Department of PharmacognosyFaculty of PharmacyCairo UniversityCairo11562Egypt; Department of ImmunologyTheodor Bilharz Research InstituteWarak El-HadarImbaba P.O. Box 30Giza12411Egypt; Department of PathologyTheodor Bilharz Research InstituteWarak El-HadarImbaba P.O. Box 30Giza12411Egypt; Department of Pharmacology and BiochemistryFaculty of PharmacyThe British University in EgyptSuez Desert RoadP.O. Box 43ElSherouk CityCairo 11837Egypt; Department of PharmacognosyFaculty of PharmacyOctober University for Modern Sciences and Arts (MSA)6th of OctoberGiza12566Egypt2020-01-092020-01-09201922254110https://doi.org/10.1016/j.jtcme.2018.01.010PubMed ID :https://t.ly/7OJlBScopusMSA Google ScholarFew studies reported the antifibrotic effects of gallic acid (GA) despite its known hepatoprotective and antioxidant activities. Accordingly, this study investigated the antifibrotic effects of GA through clarifying its mechanisms on hepatic stellate cells� (HSCs) activation, proliferation and/or apoptosis. In vitro effects of GA on HSC-T6 activation/proliferation, morphology and safety on hepatocytes were assessed. In vivo, hepatic fibrosis was induced via chronic thioacetamide (TAA)-intoxication. TAA-intoxicated rats were treated with silyamrin or GA. At end of experiment, liver functions, hepatic MDA, GSH, PDGF-BB, TGF-?1, TIMP-1 and hydroxyproline were determined. Histological analysis and Sirius red staining of hepatic sections, expressions of alpha-smooth muscle actin (?-SMA), proliferating cellular nuclear antigen (PCNA) and caspase-3 were examined. In vitro, GA resulted in a concentration and time-dependent inhibition in HSCs activation, proliferation (IC50= 45 and 19 ?g/mL at 24 and 48 h respectively); restored the quiescent morphology of some activated HSCs plus its safety on hepatocytes. In vivo, GA reduced ALT, AST, MDA, PDGF-BB levels, collagen deposition and fibrosis score (S1 vs S4); increased caspase-3 expression and restored GSH stores, TGF-?1 level, ?-SMA and PCNA expressions. In conclusion, GA counteracted the progression of hepatic fibrosis through reduction of HSCs proliferation/activation mutually with their apoptosis induction. � 2018 Center for Food and Biomolecules, National Taiwan UniversityEnglishApoptosisGallic acidHepatic stellate cellsHepatocytesProliferation/activationArticlehttps://doi.org/10.1016/j.jtcme.2018.01.010PubMed ID :