College of Medicine, Qinghai University, Xining 810016, China.
College of Ecological and Environmental Engineering, Qinghai University, Xining 810016, China.
Molecules. 2022 Mar 29;27(7):2224. 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.
本研究旨在探讨沙棘固醇（SBS）对大鼠四氯化碳（CCl）诱导急性肝损伤的疗效和保护机制。将 5 周龄雄性 Sprague-Dawley（SD）大鼠分为 6 组，分别给予生理盐水（BG 组）、50% CCl（MG 组）、双呋定 200mg/kg（DDB 组）或低剂量（LD 组）、中剂量（MD 组）、高剂量（HD 组）SBS。本研究首次观察了 SBS 对大鼠 CCl 诱导肝损伤的保护作用及其机制。酶活性研究表明，SBS 喂养的大鼠 COX-2、PGE2 和 γ-GT 活性降低，炎症病变明显减轻。此外，与 MG 组相比，SBS 治疗组肝组织中脂质过氧化增加的指标（SOD、GSH-Px、CAT、T-AOC 和 TP）和 MDA 降低，表明 SBS 具有抗脂质过氧化作用。利用广泛的靶向技术和多种手段（UPLC-MS/MS 检测平台、自建数据库和多元统计分析），发现 SBS 的添加可恢复代谢途径的表达（如 L-苹果酸、N-乙酰天冬氨酸、N-乙酰-l-丙氨酸等），减轻 CCl 引起的代谢损伤。此外，采用转录组学分析比较不同组别的基因表达水平。结果表明，SBS 调节与肝损伤相关的基因（Cyp1a1、Noct 和 TUBB6）的表达。综上所述，SBS 对大鼠 CCl 诱导的肝损伤具有保护作用。SBS 的肝保护机制可能与调节代谢紊乱、抗脂质过氧化和抑制炎症反应有关。
