Mitigation of intrahepatic cholestasis induced by 17α-ethinylestradiol via nanoformulation of Silybum marianum L.

Theodor Bilharz Research Institute

Bibliographic Information

Authors: Salem M.B.; Mohammed D.M.; Hammam O.A.; Elzallat M.

Journal: BMC Complementary Medicine and Therapies

Publisher: BioMed Central Ltd

Publication Date: 23 January 2024

Volume / Issue: Volume 24 / Issue 1

Article No.: 51

ISSN: 26627671

DOI: 10.1186/s12906-024-04351-2

Scopus: View on Scopus

PubMed: 38263002

Document Type: Article

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

Authors and Affiliations

Salem M.B., Pharmacology Department, Theodor Bilharz Research Institute, P.O. box 30, Imbaba, Warrak El-Hadar, Giza, 12411, Egypt; Mohammed D.M., Nutrition and Food Sciences Department, National Research Centre, Dokki, Giza, 12622, Egypt; Hammam O.A., Pathology Department, Theodor Bilharz Research Institute, P.O. box 30, Imbaba, Warrak El-Hadar, Giza, 12411, Egypt; Elzallat M., Immunology Department, Theodor Bilharz Research Institute, P.O. box 30, Imbaba, Warrak El-Hadar, Giza, 12411, Egypt

Abstract

Background: Cholestasis is an important predisposing factor for hepatocyte damage, liver fibrosis, primary biliary cirrhosis, and even liver failure. Silybum marianum L. (SM) plant is used in teas or eaten in some countries due to its antioxidant and hepatoprotective properties. Because of its low and poor oral bioavailability, so we improve the therapeutic activity of Silybum marianum L. extract (SM) by studying the potential effects of nanoformulation of Silybum marianium L. extract (nano-SM) on 17α-ethinylestradiol (EE)-induced intrahepatic cholestasis. Methods: Thirty female Sprague-Dawley rats were divided into 5 groups (6 rats/group). Group I: Rats were received the treatment vehicle and served as normal group. Group II:Rats were injected daily with EE (10 mg/kg) for five successive days. Group III-V: Rats were injected daily with EE (10 mg/kg) and treated with either Ursodeoxycholic acid (UDCA) (40 mg/kg), SM (100 mg/kg) and nano-SM (100 mg/kg) orally once/day throughout the trialfor five successive days, respectively. Results: Nano-SM greatly dampened the increase in serum levels of total and direct bilirubin, alanine aminotransaminase, aspartate aminotransaminase, and alkaline phosphatase caused by EE. Furthermore, nano-SM increased the hepatic contents of reduced glutathione (GSH) and catalase (CAT) and also upregulated the relative hepatic gene expressions of Rho-kinase (ROCK-1), myosin light chain kinase (MLCK), and myosin phosphatase target subunit (MYPT1) compared to the EE-induced group. Administration of nano-SM reduced hepatic lipid peroxidation and downregulated the relative hepatic expressions of the nuclear factor-kappa B (NF-ҡB) and interleukin-1β (IL-1β). In addition, nano-SM improved the histopathological changes induced by EE. Conclusion: Nano-SM possessed a superior effect over SM, which can be considered an effective protective modality against EE-induced cholestatic liver injury through its antioxidant, anti-inflammatory activities, and enhancing bile acid (BA) efflux. © 2024, The Author(s).

Keywords

Bile acid efflux; Ethinylestradiol; Inflammation; Intrahepatic cholestasis; Nanoformulation; Silybum Marianium L; Animals; Antioxidants; Asteraceae; Cholestasis, Intrahepatic; Ethinyl Estradiol; Plant Extracts; Rats; Rats, Sprague-Dawley; Silybum marianum; alanine aminotransferase; alkaline phosphatase; antiinflammatory agent; aspartate aminotransferase; bilirubin; catalase; glutathione; immunoglobulin enhancer binding protein; interleukin 1beta; malonaldehyde; myosin light chain kinase; myosin phosphatase subunit 1; nanoSilybum marianum extract; pentobarbital; rho associated protein kinase 1; Silybum marianum extract; silymarin; unclassified drug; ursodeoxycholic acid; antioxidant; plant extract; adult; animal experiment; animal model; animal tissue; antioxidant activity; Article; atomic absorption spectrometry; biological functions; controlled study; dispersity; down regulation; DPPH radical scavenging assay; drug formulation; experimental disease; female; gene expression; histopathology; IC50; immunohistochemistry; lipid peroxidation; liver injury; liver tissue; nonhuman; oxidative stress; rat; real time polymerase chain reaction; RNA extraction; transmission electron microscopy; upregulation; zeta potential; animal; Sprague Dawley rat

Citation Information

Scopus Citations: 9

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