Key Laboratory of Luminescence and Real-Time Analytical Chemistry, Ministry of Education, College of Pharmaceutical Sciences, Southwest University, Chongqing 400715, People's Republic of China.
Department of Hepatobiliry Surgery, Institute of Surgery Research, Daping Hospital, Third Military Medical University, Chongqing 400042, People's Republic of China.
Chem Biol Interact. 2014 Apr 25;213:51-9. doi: 10.1016/j.cbi.2014.02.003. Epub 2014 Feb 14.
The purpose of this study was to investigate the possible hepatoprotective effects of neohesperidin dihydrochalcone (NHDC) on carbon tetrachloride (CCl4)-induced acute oxidative injury in vivo and in vitro. In a mouse model, intraperitoneal injection of CCl4 resulted in a significant increase in serum aspartate transaminase (AST) and alanine transaminase (ALT) activities. Histopathological examination revealed severe hepatocyte necrosis and destruction of architecture in liver lesions, and immunohistochemical staining illustrated a remarkable enhancement of COX-2 and iNOS expression. The levels of hepatic antioxidant, such as, catalase (CAT), total superoxide dismutase (T-SOD), glutathione peroxidase (GP-X) and glutathione (GSH) were decreased, compared to the control group. However, pretreatment of NHDC for six consecutive days significantly ameliorated these changes. Moreover, Western blotting assay indicated pretreatment with NHDC also down-regulated CCl4-induced protein expressions of NF-κB, IL-6, caspase 3 and caspase 8. In HepG2 cell model, CCl4-treatment caused significant decrease in cell viability, antioxidant activities and GSH level, increase in intracellular reactive oxygen species (ROS) and thiobarbituric acid reactive substances (TBARS) level. Interestingly, pretreatment of NHDC effectively relieved CCl4-induced oxidative damage in a dose-dependent manner. In conclusion, NHDC appeared to possess promising anti-oxidative and anti-inflammatory capacities, it is possible to be used as a hepatoprotective agent.
本研究旨在探讨新橙皮苷二氢查尔酮（NHDC）对体内外四氯化碳（CCl4）诱导的急性氧化损伤的可能肝保护作用。在小鼠模型中，腹腔注射 CCl4 导致血清天冬氨酸转氨酶（AST）和丙氨酸转氨酶（ALT）活性显著增加。组织病理学检查显示肝损伤部位严重的肝细胞坏死和结构破坏，免疫组织化学染色显示 COX-2 和 iNOS 表达显著增强。与对照组相比，肝抗氧化剂如过氧化氢酶（CAT）、总超氧化物歧化酶（T-SOD）、谷胱甘肽过氧化物酶（GP-X）和谷胱甘肽（GSH）的水平降低。然而，连续 6 天预处理 NHDC 可显著改善这些变化。此外，Western blot 分析表明，NHDC 预处理还下调了 CCl4 诱导的 NF-κB、IL-6、caspase 3 和 caspase 8 蛋白表达。在 HepG2 细胞模型中，CCl4 处理导致细胞活力、抗氧化活性和 GSH 水平显著降低，细胞内活性氧（ROS）和硫代巴比妥酸反应物质（TBARS）水平增加。有趣的是，NHDC 的预处理以剂量依赖的方式有效缓解了 CCl4 诱导的氧化损伤。综上所述，NHDC 似乎具有有前途的抗氧化和抗炎能力，有可能用作肝保护剂。
