College of Chinese Medicinal Materials , Jilin Agricultural University , Changchun , Jilin 130118 , People's Republic of China.
Department of Anesthesiology , Changchun Shuangyang District Hospital , Changchun , Jilin 130600 , People's Republic of China.
J Agric Food Chem. 2018 Jul 25;66(29):7758-7763. doi: 10.1021/acs.jafc.8b02627. Epub 2018 Jul 16.
It is reported that sesquiterpenoids from Panax ginseng (SPG) possess various pharmacological activities, for example, antidepressant, antioxidative, and anti-inflammatory activities. The purpose of this study was to examine the hepatoprotective effects of SPG (2.5 and 10 mg/kg, i.g.) on fulminant liver injury induced by d-galactosamine (d-GalN) and lipopolysaccharide (LPS) and discuss its mechanisms of action. After 24 h of d-GalN (400 mg/kg, i.p.) and LPS (25 μg/kg, i.p.) exposure, the serum levels of alanine transaminase (ALT) and aspartate transaminase (AST), hepatic malondialdehyde (MDA) level, hepatic activities of superoxide dismutase (SOD), catalase (CAT), and glutathione (GSH), and hepatic tissue histology were measured. Expression levels of tumor necrosis factor α (TNF-α) and interleukin-1β (IL-1β) were detected by enzyme-linked immunosorbent assay and real-time polymerase chain reaction. Moreover, the nuclear factor κ-light-chain-enhancer of activated B cell (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), sirtuin type 1 (Sirt 1), and heme oxygenase 1 (HO-1) were determined by western blotting. The results indicated that SPG evidently restrained the increase of serum ALT and AST levels induced by d-GalN/LPS. SPG obviously downregulated TNF-α and IL-1β levels and their mRNA expression in liver. In addition, d-GalN/LPS injection induced severe oxidative stress in liver by boosting the MDA level as well as decreasing CAT, GSH, and SOD capacities, and SPG reversed these changes. Meanwhile, SPG inhibited NF-κB activation induced by d-GalN/LPS and upregulated Sirt 1, Nrf2, and HO-1 expression levels. Therefore, SPG might protect against the fulminant liver injury induced by d-GalN/LPS via inhibiting inflammation and oxidative stress. The protective effect of SPG on fulminant liver injury induced by d-GalN/LPS might be mediated by the Sirt 1/Nrf2/NF-κB signaling pathway. All of these results implied that SPG might be a promising food additive and therapeutic agent for fulminant liver injury.
据报道，人参中的倍半萜类化合物具有多种药理活性，例如抗抑郁、抗氧化和抗炎活性。本研究旨在探讨人参（2.5 和 10mg/kg，ig）对半乳糖胺（d-GalN）和脂多糖（LPS）诱导的暴发性肝损伤的保护作用，并探讨其作用机制。在给予 d-GalN（400mg/kg，ip）和 LPS（25μg/kg，ip）24 小时后，测定血清丙氨酸转氨酶（ALT）和天冬氨酸转氨酶（AST）水平、肝丙二醛（MDA）水平、肝超氧化物歧化酶（SOD）、过氧化氢酶（CAT）和谷胱甘肽（GSH）的活性，以及肝组织学变化。采用酶联免疫吸附试验和实时聚合酶链反应检测肿瘤坏死因子-α（TNF-α）和白细胞介素-1β（IL-1β）的表达水平。此外，通过 Western 印迹法测定核因子κ轻链增强子的 B 细胞（NF-κB）、红细胞生成素相关因子 2（Nrf2）、Sirtuin 1（Sirt 1）和血红素加氧酶 1（HO-1）。结果表明，人参明显抑制了 d-GalN/LPS 诱导的血清 ALT 和 AST 水平升高。人参明显下调了肝组织 TNF-α和 IL-1β水平及其 mRNA 表达。此外，d-GalN/LPS 注射通过提高 MDA 水平以及降低 CAT、GSH 和 SOD 能力，导致肝脏发生严重氧化应激，而人参则逆转了这些变化。同时，人参抑制了 d-GalN/LPS 诱导的 NF-κB 激活，并上调了 Sirt 1、Nrf2 和 HO-1 的表达水平。因此，人参可能通过抑制炎症和氧化应激来防止 d-GalN/LPS 诱导的暴发性肝损伤。人参对 d-GalN/LPS 诱导的暴发性肝损伤的保护作用可能是通过 Sirt 1/Nrf2/NF-κB 信号通路介导的。所有这些结果表明，人参可能是一种有前途的暴发性肝损伤食品添加剂和治疗药物。
