Investigating the hepatoprotective potentiality of marine-derived steroids as promising inhibitors of liver fibrosis.
Mohamed A Tammam, Florbela Pereira, Omnia Aly, Mohamed Sebak, Yasser M Diab, Aldoushy Mahdy, Amr El-Demerdash
Author Information
Mohamed A Tammam: Department of Biochemistry, Faculty of Agriculture, Fayoum University Fayoum 63514 Egypt. ORCID
Florbela Pereira: LAQV REQUIMTE, Department of Chemistry, NOVA School of Science and Technology, Universidade Nova de Lisboa 2829516 Caparica Portugal. ORCID
Omnia Aly: Department of Medical Biochemistry, National Research Centre Cairo 12622 Egypt.
Mohamed Sebak: Microbiology and Immunology Department, Faculty of Pharmacy, Beni-Suef University Egypt. ORCID
Yasser M Diab: Department of Biochemistry, Faculty of Agriculture, Fayoum University Fayoum 63514 Egypt.
Aldoushy Mahdy: Department of Zoology, Faculty of Science, Al-Azhar University (Assiut Branch) Assiut 71524 Egypt.
Amr El-Demerdash: Division of Organic Chemistry, Department of Chemistry, Faculty of Sciences, Mansoura University Mansoura 35516 Egypt a_eldemerdash83@mans.edu.eg Amr.El-Demerdash@jic.ac.uk. ORCID
It has been reported that organic extracts derived from soft corals belonging to the genus have exhibited a wide range of therapeutic characteristics. Based on biochemical and histological techniques, we aimed to assess the hepatoprotective role of the organic extract and its principal steroidal contents derived from the Red Sea soft coral on acetaminophen-induced liver fibrosis in rats. Serum liver function parameters (ALT, AST, ALP and total bilirubin) were quantified using a spectrophotometer, and both alpha-fetoprotein (AFP) and carcinoembryonic antigen (CEA) levels were determined by using enzyme-linked immunosorbent assay (ELISA) kits while transformed growth factor beta (TGF-β) and tumor necrosis factor α (TNF-α) in liver tissue homogenate were determined using ELISA, and TGF-β and TNF-α gene expression in liver tissue was determined using real-time PCR following extraction and purification. Histopathological alterations in hepatic tissue were also examined under a microscope. In order to prioritize the isolation and characterization of the most promising marine steroids from the organic extract of the Red Sea soft coral as hepatoprotective agents, a computational approach was employed. This approach involved molecular docking (MDock) and analysis of the structure-activity relationship (SAR) against glutathione--transferase (GST) and Cu-Zn human superoxide dismutase (Cu-ZnSOD) enzymes. Although the major role in the detoxification of foreign chemicals and toxic metabolites of GST and SOD enzymes is known, there is a lack of knowledge about the mode of action of the hepatoprotective process and those of the targets involved. The present study investigated the multiple interactions of a series of marine steroids with the GST and SOD enzymes, in order to reveal insights into the process of hepatoprotection.
