Antifibrotic effects of gallic acid on hepatic stellate cells: mechanistic study.

Journal: Journal of traditional and complementary medicine
Published Date: Apr 27, 2018

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. effects of GA on HSC-T6 activation/proliferation, morphology and safety on hepatocytes were assessed. , hepatic fibrosis was induced 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. , GA resulted in a concentration and time-dependent inhibition in HSCs activation, proliferation (IC= 45 and 19 μg/mL at 24 and 48 h respectively); restored the quiescent morphology of some activated HSCs plus its safety on hepatocytes. , 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.

Authors

  • Naglaa M El-Lakkany
    Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza 12411, Egypt.
  • Walaa H El-Maadawy
    Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza 12411, Egypt.
  • Sayed H Seif El-Din
    Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza 12411, Egypt.
  • Samira Saleh
    Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
  • Marwa M Safar
    Department of Pharmacology and Toxicology, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
  • Shahira M Ezzat
    Department of Pharmacognosy, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
  • Salwa H Mohamed
    Department of Immunology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza 12411, Egypt.
  • Sanaa S Botros
    Department of Pharmacology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza 12411, Egypt.
  • Zeinab Demerdash
    Department of Immunology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza 12411, Egypt.
  • Olfat A Hammam
    Department of Pathology, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza 12411, Egypt.

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