Hydroxysafflor yellow A protects against thioacetamide-induced liver fibrosis in rats via suppressing proinflammatory/fibrogenic mediators and promoting hepatic stellate cell senescence and apoptosis

Theodor Bilharz Research Institute

Bibliographic Information

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

Journal: Asian Pacific Journal of Tropical Biomedicine

Publisher: Wolters Kluwer Medknow Publications

Publication Date: 23 August 2023

Volume / Issue: Volume 13 / Issue 8

Pages: 348–358

ISSN: 22211691

DOI: 10.4103/2221-1691.383689

Scopus: View on Scopus

Document Type: Article

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

Authors and Affiliations

Seif El-Din S.H., Pharmacology Department, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza, 12411, Egypt; Hammam O.A., Pathology Department, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza, 12411, Egypt; Ezzat S.M., Pharmacognosy Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt, Pharmacognosy Department, Faculty of Pharmacy, October University for Modern Sciences and Arts, Giza, Egypt; Saleh S., Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt; Safar M.M., Pharmacology and Toxicology Department, Faculty of Pharmacy, Cairo University, Cairo, 11562, Egypt, Pharmacology and Biochemistry Department, Faculty of Pharmacy, The British University in Egypt, Cairo, Egypt; El-Maadawy W.H., Pharmacology Department, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza, 12411, Egypt; El-Lakkany N.M., Pharmacology Department, Theodor Bilharz Research Institute, Warak El-Hadar, Imbaba P.O. Box 30, Giza, 12411, Egypt

Abstract

Objective: To evaluate the effect of hydroxysafflor yellow A (HSYA) on thioacetamide-induced liver fibrosis. Methods: Thioacetamide was administered to rats intraperitoneally in doses of 200 mg/kg twice a week for 12 weeks. Thioacetamide-intoxicated rats were given silymarin (50 mg/kg) or HSYA (5 mg/ kg) orally every day for 8 weeks. Liver enzymes, fibrosis markers, histological changes as well as immunohistochemistry of TNF-α, IL-6, p21, α-SMA, and caspase-3 were examined. The effect of HSYA on HSC-T6 activation/proliferation and apoptosis was also determined in vitro. Results: HSYA decreased liver enzymes, TNF-α, IL-6, and p21 expressions, hepatic PDGF-B, TIMP-1, TGF-β1, and hydroxyproline levels, as well as fibrosis score (S2 vs. S4) compared to the thioacetamide group. HSYA also downregulated α-SMA while increasing caspase-3 expression. Surprisingly, at 500 μg/mL, HSYA had only a slightly suppressive effect on HSC proliferation, with a 9.5% reduction. However, it significantly reduced TGF-β1, inhibited α-SMA expression, induced caspase-3 expression, and promoted cell senescence. Conclusions: HSYA may be a potential therapeutic agent for delaying and reversing the progression of liver fibrosis. More research on HSYA at higher doses and for a longer period is warranted. ©2023 Asian Pacific Journal of Tropical Biomedicine Produced by Wolters Kluwer-Medknow.

Keywords

Apoptosis; Hepatic stellate cells; Hydroxysafflor yellow A; Inflammatory markers; Liver fibrosis; p21; Thioacetamide; α-SMA; alpha smooth muscle actin; caspase 3; hydroxyproline; interleukin 6; liver enzyme; liver protective agent; plant extract; platelet derived growth factor B; silymarin; tissue inhibitor of metalloproteinase 1; transforming growth factor beta1; tumor necrosis factor; unclassified drug; adult; animal experiment; animal model; antiinflammatory activity; Article; cell aging; cell proliferation; controlled study; down regulation; flower; hepatic stellate cell; HSC-T6 cell line; immunohistochemistry; in vitro study; in vivo study; liver protection; male; nonhuman; rat; safflower; thioacetamide-induced liver fibrosis

Citation Information

Scopus Citations: 5

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