Qiu Bing-Xun, Liu Ke, Zou Li, Zhu Hui-Feng, Feng Shan
College of Pharmaceutical Sciences and Chinese Medicine, Southwest University, Chongqing 400715, China.
Sichuan Vocational College of Health and Rehabilitation, Zigong 643000, China.
Zhongguo Zhong Yao Za Zhi. 2018 Dec;43(24):4908-4915. doi: 10.19540/j.cnki.cjcmm.20180625.006.
Schisandra chinensis is a commonly used hepatoprotective medicine in clinic. Previous studies have showed that Schisandrae Chinensis Fructus has dual effects on the activity of CYPs. Short-term administration of Schisandrae Chinensis Fructus may inhibit CYP450s activity, while long-term administration may up-regulate CYP activity. High CYP450s activity level may increase the frequency of reactive metabolites-induced liver injury. It remains unclear how long-term administration of Schisandrae Chinensis Fructus may affect acetaminophen-induced acute hepatotoxicity. After oral administration of Schisandrae Chinensis Fructus extract (0.5-2.0 g·kg⁻¹) for 21 d, the activity of CYPs, Nrf2, HO-1, GST expressions, SOD and GST activity as well as glutathione level of SD rats were up-regulated. Besides, Schisandrae Chinensis Fructus extract ameliorated APAP (500 mg·kg⁻¹)-induced acute hepatotoxicity in a dose-dependent manner, as evidenced by decrease in ALT, AST, and MDA level and increase in GSH level (<0.05). What's more, the liver histopathology was alleviated, and cleaved caspase-3 expression was decreased. Besides, the increase of N-acetyl-p-benzoquinoneimine-GSH (reactive metabolite of acetaminophen) formation was observed in Schisandrae Chinensis Fructus extract groups. In conclusion, the present study indicated that the effects of Schisandrae Chinensis Fructuson acetaminophen-induced hepatotoxicity may rely on the Nrf2 signal pathway activation, and less depends on the increase in CYP450s activity.
五味子是临床上常用的保肝药物。以往研究表明，五味子果实对细胞色素P450酶（CYPs）的活性具有双重作用。短期服用五味子果实可能会抑制CYP450酶的活性，而长期服用则可能上调CYP酶的活性。较高的CYP450酶活性水平可能会增加反应性代谢产物诱导的肝损伤频率。长期服用五味子果实如何影响对乙酰氨基酚诱导的急性肝毒性仍不清楚。给SD大鼠口服五味子果实提取物（0.5 - 2.0 g·kg⁻¹）21天后，大鼠的CYP酶活性、核因子E2相关因子2（Nrf2）、血红素加氧酶-1（HO-1）、谷胱甘肽S-转移酶（GST）的表达、超氧化物歧化酶（SOD）和GST的活性以及谷胱甘肽水平均上调。此外，五味子果实提取物以剂量依赖性方式改善了对乙酰氨基酚（500 mg·kg⁻¹）诱导的急性肝毒性，表现为谷丙转氨酶（ALT）、谷草转氨酶（AST）和丙二醛（MDA）水平降低以及谷胱甘肽（GSH）水平升高（P<0.05）。此外，肝脏组织病理学得到缓解，裂解的半胱天冬酶-3表达降低。此外，在五味子果实提取物组中观察到对乙酰氨基酚的反应性代谢产物N-乙酰对苯醌亚胺-GSH的形成增加。总之，本研究表明五味子果实对乙酰氨基酚诱导的肝毒性的影响可能依赖于Nrf2信号通路的激活，而较少依赖于CYP450酶活性的增加。
