Rutin Ameliorates Hepatic Fibrosis via Targeting Hepatic Stellate Cells’ Activation, Proliferation and Apoptosis

Theodor Bilharz Research Institute

Bibliographic Information

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

Journal: Journal of Herbs, Spices and Medicinal Plants

Publisher: Bellwether Publishing, Ltd.

Publication Date: 30 April 2021

Volume / Issue: Volume 27 / Issue 3

Pages: 322–341

ISSN: 10496475

DOI: 10.1080/10496475.2021.1911905

Scopus: View on Scopus

Document Type: Article

Authors and Affiliations

El-Maadawy W.H., Pharmacology Department, Theodor Bilharz Research Institute, Giza, Egypt; Seif el-Din S.H., Pharmacology Department, Theodor Bilharz Research Institute, Giza, Egypt; Ezzat S.M., Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt, Pharmacognosy Department, Faculty of Pharmacy, October University for Modern Sciences and Arts, Giza, Egypt; Hammam O.A., Pathology Department, Theodor Bilharz Research Institute, Giza, Egypt; Safar M.M., Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt, Pharmacology and Biochemistry Department, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; Saleh S., Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt; El-Lakkany N.M., Pharmacology Department, Theodor Bilharz Research Institute, Giza, Egypt

Abstract

Despite rutin, extracted from black mulberry, has several pharmacological activities, its exact effect against hepatic fibrosis remains incompletely identified. Accordingly, this study investigates whether rutin is a promising candidate for treating hepatic fibrosis and to clarify its underlying antifibrotic mechanisms in vitro and in vivo. In vitro studies were performed on hepatic stellate cell line (HSC-T6) whereas liver fibrosis was established in rats via chronic thioacetamide (TAA)-intoxication. Rats were divided into (i) normal, (ii) TAA-intoxicated rats; TAA-intoxicated rats treated with (iii) silymarin or (iv) rutin. Levels of ALT, AST, platelet-derived growth factor-BB (PDGF-BB), tissue inhibitor metalloproteinases type-1 (TIMP-1), hydroxyproline and expression of proliferating cellular nuclear antigen (PCNA) together with histological changes were examined. Activities of rutin on TGF-β1, α-smooth muscle actin (α-SMA) and caspase-3 were measured in vitro and in vivo. Rutin exhibited no marked HSC-T6 cell death (IC50 = 460 µg.ml−1), however, it showed reduction in HSCs activation (low TGF-β1 level and α-SMA positive cells) and induced apoptosis (high caspase-3 positive cells). Rutin also ameliorated liver functions, reduced hepatic levels of PDGF-BB, TGF-β1, TIMP-1, hydroxyproline and restored PCNA, together with attenuation in fibrosis score (S1 vs S4). Rutin could be a promising candidate for treating hepatic fibrosis through down-regulation of HSCs activation and induction of apoptosis. © 2021 Taylor & Francis Group, LLC.

Keywords

fibrosis markers; hepatic stellate-T6; in vitro; in vivo; Rutin; Morus nigra; alpha smooth muscle actin; caspase 3; cell nucleus antigen; cycline; hydroxyproline; platelet derived growth factor BB; rutoside; silymarin; smooth muscle actin; thioacetamide; tissue inhibitor of metalloproteinase 1; transforming growth factor beta1; antigen; apoptosis; cell; enzyme; growth response; inhibitor; muscle; rodent; alanine aminotransferase blood level; animal cell; animal experiment; animal model; Article; aspartate aminotransferase level; cell activation; cell proliferation; controlled study; down regulation; enzyme activity; hepatic stellate cell; human; human cell; IC50; in vitro study; in vivo study; liver cell line; liver fibrosis; liver function; male; nonhuman; protein expression; protein function; rat

Citation Information

Scopus Citations: 9

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