Metabolomic Profiling Reveals Protective Effects and Mechanisms of Sea Buckthorn Sterol against Carbon Tetrachloride-Induced Acute Liver Injury in Rats

• Published in: Molecules (Basel, Switzerland) Vol. 27; no. 7; p. 2224
• Main Authors: Sheng, Changting, Guo, Yang, Ma, Jing, Hong, Eun-Kyung, Zhang, Benyin, Yang, Yongjing, Zhang, Xiaofeng, Zhang, Dejun
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 29.03.2022; MDPI
• Subjects: acute liver injury; Alanine; Alanine Transaminase - metabolism; Animals; Antioxidants; Antioxidants - pharmacology; Aspartic acid; Biotechnology; Carbon tetrachloride; Carbon Tetrachloride - adverse effects; Catalase; Chemical and Drug Induced Liver Injury - drug therapy; Chemical and Drug Induced Liver Injury - metabolism; Chemical and Drug Induced Liver Injury - prevention & control; Chemical and Drug Induced Liver Injury, Chronic - drug therapy; Chromatography, Liquid; Cyclooxygenase-2; Cytochrome P450; Enzymatic activity; Enzymes; Gene expression; Glutathione peroxidase; Hippophae - metabolism; Inflammation; Inflammatory response; L-Alanine; Lipid Peroxidation; Lipids; Liver; Male; Malic acid; Metabolic disorders; Metabolic pathways; Metabolism; Metabolomics; Multivariate statistical analysis; Oral administration; Oxidation; Oxidative Stress; Peroxidase; Peroxidation; Plant Extracts - pharmacology; Prostaglandin E2; Proteins; Rats; Rats, Sprague-Dawley; sea buckthorn sterol; Seeds; Statistical analysis; Sterols; Sterols - pharmacology; Superoxide dismutase; Tandem Mass Spectrometry; Transcriptomics; γ-Glutamyltransferase; China; carbon tetrachloride; metabolomics; sea buckthorn sterol; acute liver injury
• ISSN: 1420-3049; 1420-3049
• DOI: 10.3390/molecules27072224

The present study was designed to examine the efficacy and protection mechanisms of sea buckthorn sterol (SBS) against acute liver injury induced by carbon tetrachloride (CCl ) in rats. Five-week-old male Sprague-Dawley (SD) rats were divided into six groups and fed with saline (Group BG), 50% CCl (Group MG), or bifendate 200 mg/kg (Group DDB), or treated with low-dose (Group LD), medium-dose (Group MD), or high-dose (Group HD) SBS. This study, for the first time, observed the protection of SBS against CCl -induced liver injury in rats and its underlying mechanisms. Investigation of enzyme activities showed that SBS-fed rats exhibited a significant alleviation of inflammatory lesions, as evidenced by the decrease in cyclooxygenase-2 (COX-2), prostaglandin E2 (PGE2), and gamma-glutamyl transpeptidase (γ-GT). In addition, compared to the MG group, the increased indices (superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), total antioxidant capacity (T-AOC), and total protein (TP)) of lipid peroxidation and decreased malondialdehyde (MDA) in liver tissues of SBS-treated groups showed the anti-lipid peroxidation effects of SBS. Using the wide range of targeted technologies and a combination of means (UPLC-MS/MS detection platform, self-built database, and multivariate statistical analysis), the addition of SBS was found to restore the expression of metabolic pathways (e.g., L-malic acid, N-acetyl-aspartic acid, N-acetyl-l-alanine, etc.) in rats, which means that the metabolic damage induced by CCl was alleviated. Furthermore, transcriptomics was employed to analyze and compare gene expression levels of different groups. It showed that the expressions of genes (Cyp1a1, Noct, and TUBB6) related to liver injury were regulated by SBS. In conclusion, SBS exhibited protective effects against CCl -induced liver injury in rats. The liver protection mechanism of SBS is probably related to the regulation of metabolic disorders, anti-lipid peroxidation, and inhibition of the inflammatory response.