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

Maha B Salem; Dina Mostafa Mohammed; Olfat A Hammam; Mohamed Elzallat

doi:10.1186/s12906-024-04351-2

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

BMC Complement Med Ther. 2024 Jan 23;24(1):51. doi: 10.1186/s12906-024-04351-2.

Authors

Maha B Salem¹, Dina Mostafa Mohammed², Olfat A Hammam³, Mohamed Elzallat⁴

Affiliations

¹ Pharmacology Department, Theodor Bilharz Research Institute, P.O. box 30, Warrak El-Hadar, Giza, 12411, Imbaba, Egypt.
² Nutrition and Food Sciences Department, National Research Centre, Dokki, Giza, 12622, Egypt. dm.mahdy@nrc.sci.eg.
³ Pathology Department, Theodor Bilharz Research Institute, P.O. box 30, Warrak El-Hadar, Giza, 12411, Imbaba, Egypt.
⁴ Immunology Department, Theodor Bilharz Research Institute, P.O. box 30, Warrak El-Hadar, Giza, 12411, Imbaba, 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.

Keywords: Bile acid efflux; Ethinylestradiol; Inflammation; Intrahepatic cholestasis; Nanoformulation; Silybum Marianium L..

MeSH terms

Animals
Antioxidants
Asteraceae*
Cholestasis, Intrahepatic*
Ethinyl Estradiol
Plant Extracts
Rats
Rats, Sprague-Dawley
Silybum marianum

Substances

Ethinyl Estradiol
Antioxidants
Plant Extracts