School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, PR China.
School of Chemistry and Chemical Engineering, Harbin Institute of Technology, Harbin, 150001, PR China.
Food Chem Toxicol. 2020 Aug;142:111490. doi: 10.1016/j.fct.2020.111490. Epub 2020 Jun 12.
Previously, we obtained a purified polysaccharide (PNP40c-1) from Pinus koraiensis pine nut and reported its protective effect on carbon tetrachloride (CCl)-induced liver injury in vitro. The object of this study is to investigate its hepatoprotective activity in vivo and elucidate the mechanism underlying the hepatoprotection. PNP40c-1 effectively prevented the accumulation of serum liver injury biomarkers including alanine aminotransferase, aspartate aminotransferase, alkaline phpsphatase and total bilirubin stimulated by CCl. The pathological changes in PNP40c-1-treated mice livers were also markedly ameliorated. Results showed that PNP40c-1 suppressed the production of reactive oxygen species (ROS) and lipid peroxidation, upregulated Nrf2/ARE pathway and enhanced the antioxidant capacity of hepatocytes. Furthermore, the reaction between Nrf2 and ARE promoted the generation of Mkp1, which inhibited the activation of JNK induced by CCl, and suppressed hepatocytes apoptosis by regulating the protein expression of Bax, cleaved-Caspase-3 and Bcl2, exerting hepatoprotective activity. Taken together, upregulation of Nrf2/ARE pathway and suppression of JNK activation via Nrf2/ARE/Mkp1/JNK signaling pathways are the main mechanisms underlying the hepatoprotective effect of PNP40c-1 against CCl-induced mice liver injury. These results indicated that PNP40c-1 has potential to serve as a hepatoprotective agent against chemical induced hepatotoxicity.
先前，我们从红松松子中提取了一种纯化多糖（PNP40c-1），并报道了它对体外四氯化碳（CCl）诱导的肝损伤的保护作用。本研究的目的是在体内研究其对肝的保护活性，并阐明其肝保护作用的机制。PNP40c-1 可有效防止 CCl 刺激引起的血清肝损伤生物标志物（包括丙氨酸氨基转移酶、天冬氨酸氨基转移酶、碱性磷酸酶和总胆红素）的积累。经 PNP40c-1 处理的小鼠肝脏的病理变化也得到明显改善。结果表明，PNP40c-1 抑制活性氧（ROS）和脂质过氧化的产生，上调 Nrf2/ARE 途径并增强肝细胞的抗氧化能力。此外，Nrf2 与 ARE 的反应促进了 Mkp1 的生成，抑制了 CCl 诱导的 JNK 的激活，并通过调节 Bax、cleaved-Caspase-3 和 Bcl2 的蛋白表达来抑制肝细胞凋亡，发挥肝保护作用。总之，上调 Nrf2/ARE 途径和抑制 JNK 激活是 PNP40c-1 通过 Nrf2/ARE/Mkp1/JNK 信号通路发挥对 CCl 诱导的小鼠肝损伤保护作用的主要机制。这些结果表明，PNP40c-1 有潜力成为一种针对化学诱导肝毒性的肝保护剂。
