Shaanxi University of Technology, College of Biological Science and Engineering, Chinese-German Joint Laboratory for Natural Product Research, Hanzhong, Shaanxi, China.
Ministry of Education, Biotechnology Research Department, Kyaukse, Myanmar.
J Appl Biomed. 2021 May;19(2):105-112. doi: 10.32725/jab.2021.011. Epub 2021 Apr 26.
This study evaluates the protective effect of Echinacoside on acute liver toxicity induced by acetaminophen in mice and the mechanism behind it. Echinacoside and N-Acetyl Cysteine were intragastrically administrated for 7 days, and acetaminophen was intraperitoneally injected into mice 1 h after the last treatment on day 7. At the end of the experimental period, histological examination, parameters for the level of oxidative damage, hepatic malondialdehyde, serum pro-inflammatory cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-1β), UDP-glucuronosyltransferases, and sulfotransferases changes were examined using enzyme-linked immunosorbent assay and standard biochemical procedures. The expression of cytochrome P450 2E1 protein was assessed by western blot, followed by in silico molecular docking. Acetaminophen treatment obviously increased the levels of ALT and AST, changed hepatic histopathology, promoted oxidative stress, decreased antioxidant enzyme activities, and elevated the pro-inflammatory cytokines. Echinacoside significantly attenuated Acetaminophen-induced liver damage in a dose-dependent manner, with the most effective dose at 100 mg/kg. The pretreatments of Echinacoside in different concentrations altered the Acetaminophen-induced hepatotoxicity levels by decreasing the level of liver enzymes, reducing the liver necrosis with vacuolization, decreasing the hepatic malondialdehyde formation, increasing hepatic antioxidants activities, suppressing the pro-inflammatory cytokines (Tumor Necrosis Factor, Interleukin-6 and Interleukin-1beta), inhibiting Nitric Oxide production, enhancing sulfotransferases and UDP-glucuronosyltransferases activities. Notably, the expression of cytochrome P450 2E1 was inhibited by Echinacoside in a dose-dependent manner and the binding energy was -214.3 MeV. Echinacoside showed a significant protective effect against Acetaminophen-induced hepatotoxicity through the inhibition of oxidative stress, the expression of pro-inflammatory cytokines and cytochrome P450 2E1 protein expression.
这项研究评估了松果菊苷对乙酰氨基酚诱导的小鼠急性肝毒性的保护作用及其机制。松果菊苷和 N-乙酰半胱氨酸连续 7 天灌胃，第 7 天末次给药 1 小时后，腹腔注射乙酰氨基酚。实验结束时，通过酶联免疫吸附试验和标准生化程序检测组织学检查、氧化损伤水平、肝丙二醛、血清促炎细胞因子（肿瘤坏死因子-α、白细胞介素-6 和白细胞介素-1β）、UDP-葡糖醛酸基转移酶和磺基转移酶变化。采用 Western blot 法检测细胞色素 P450 2E1 蛋白的表达，并进行计算机分子对接。乙酰氨基酚处理明显增加 ALT 和 AST 水平，改变肝组织病理学，促进氧化应激，降低抗氧化酶活性，并升高促炎细胞因子。松果菊苷呈剂量依赖性显著减轻乙酰氨基酚引起的肝损伤，以 100mg/kg 时作用最明显。松果菊苷在不同浓度预处理通过降低肝酶水平、减少肝坏死伴空泡化、减少肝丙二醛形成、增加肝抗氧化剂活性、抑制促炎细胞因子（肿瘤坏死因子、白细胞介素-6 和白细胞介素-1β）、抑制一氧化氮产生、增强磺基转移酶和 UDP-葡糖醛酸基转移酶活性来改变乙酰氨基酚诱导的肝毒性水平。值得注意的是，细胞色素 P450 2E1 的表达被松果菊苷呈剂量依赖性抑制，结合能为-214.3 MeV。松果菊苷通过抑制氧化应激、促炎细胞因子和细胞色素 P450 2E1 蛋白表达，对乙酰氨基酚诱导的肝毒性具有显著的保护作用。
