Antifibrotic effects of gallic acid on hepatic stellate cells: In vitro and in vivo mechanistic study

Theodor Bilharz Research Institute

Bibliographic Information

Authors: El-Lakkany N.M.; El-Maadawy W.H.; Seif el-Din S.H.; Saleh S.; Safar M.M.; Ezzat S.M.; Mohamed S.H.; Botros S.S.; Demerdash Z.; Hammam O.A.

Journal: Journal of Traditional and Complementary Medicine

Publisher: National Taiwan University

Publication Date: January 2019

Volume / Issue: Volume 9 / Issue 1

Pages: 45–53

ISSN: 22254110

DOI: 10.1016/j.jtcme.2018.01.010

Scopus: View on Scopus

Document Type: Article

Access: All Open Access; Gold Open Access; Green Open Access

Authors and Affiliations

El-Lakkany N.M., Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza, 12411, Egypt; El-Maadawy W.H., Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza, 12411, Egypt; Seif el-Din S.H., Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza, 12411, Egypt; Saleh S., Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt; Safar M.M., Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt, Department of Pharmacology and Biochemistry, Faculty of Pharmacy, The British University in Egypt, Suez Desert Road, P.O. Box 43, ElSherouk City, 11837, Cairo, Egypt; Ezzat S.M., Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt, Department of Pharmacognosy, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), 6th of October, Giza, 12566, Egypt; Mohamed S.H., Department of Immunology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza, 12411, Egypt; Botros S.S., Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza, 12411, Egypt; Demerdash Z., Department of Immunology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza, 12411, Egypt; Hammam O.A., Department of Pathology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza, 12411, Egypt

Abstract

Few 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-β1, TIMP-1 and hydroxyproline were determined. Histological analysis and Sirius red staining of hepatic sections, expressions of alpha-smooth muscle actin (α-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 μg/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-β1 level, α-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 University

Keywords

Apoptosis; Gallic acid; Hepatic stellate cells; Hepatocytes; Proliferation/activation

Citation Information

Scopus Citations: 44

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