Evaluation of the protective effect of Zhi-Zi-da-Huang decoction on acute liver injury with cholestasis induced by α-naphthylisothiocyanate in rats
Evaluation of the protective effect of Zhi-Zi-da-Huang decoction on acute liver injury with cholestasis induced by α-naphthylisothiocyanate in rats
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DOI：
10.1016/j.jep.2015.06.043
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发表时间：
2015-08-22
影响因子：
5.4
通讯作者：
Yin, Ran
中科院分区：
文献类型：
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作者：
Chen, Ke-Lin;Bi, Kai-Shun;Yin, Ran
民族药理学相关性：芝子大黄汤（ZZDHD）是一种由四种中草药组成的经典中药配方，在中国长期被广泛用于治疗各种肝胆疾病。然而，ZZDHD对肝损伤合并胆汁淤积的药理作用尚不清楚。目的：探讨ZZDHD对α -萘基异硫氰酸酯（ANIT）所致大鼠肝损伤伴胆汁淤积的保护作用。材料与方法：大鼠分别以1、2、4 g/kg（生药/体重）剂量灌胃ZZDHD，每天1次，连用7 d，第5次给药后12 h再灌胃ANIT (75 mg/kg)，造成肝损伤。在ANIT治疗后48 h测定血清丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）、碱性磷酸酶（ALP）、γ -谷氨酰转肽酶（γ - gtp）、总胆红素（TBIL）、直接胆红素（DBIL）、总胆汁酸（TBA）水平及胆汁流量，评价ZZDHD的保护作用。此外，通过测定肝脏酶活性和丙二醛（MDA）、髓过氧化物酶（MPO）、脂质过氧化物酶（LPG）、超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GPx）和过氧化氢酶（CAT）含量，阐明了可能的保护机制。组织病理学检查补充生化观察。采用超快速液相色谱-质谱法（UFLC-MS）对ZZDHD进行植物化学分析。结果：高剂量（4 g/kg）和中剂量（2 g/kg） ZZDHD通过逆转胆汁流量、血清和肝酶以及肝组织病理学的变化，对anit诱导的肝损伤合并胆汁淤积表现出显著的剂量依赖性保护作用。同时发现，低剂量（1 g/kg） ZZDHD对除血清TBIL、DBIL和TBA外的其他生化指标均无改善作用，保护作用不明显。植物化学分析表明，该植物中含有16种化合物。结论：本研究提示ZZDHD对anit诱导的肝损伤合并胆汁淤积大鼠具有保护肝脏的作用，其作用机制可能与其抗氧化作用有关。2015爱思唯尔爱尔兰有限公司版权所有。
Ethnopharmacological relevance: Zhi-Zi-Da-Huang decoction (ZZDHD), a classic traditional Chinese medicine (TCM) formula composed of four herbal medicines, has been widely used to treat various hepatobiliary disorders for a long time in China. However, the pharmacological effect of ZZDHD on liver injury with cholestasis is unrevealed.Aim of the study: To investigate the hepatoprotective effect of ZZDHD against alpha-naphthylisothiocyanate (ANIT)-induced liver injury with cholestasis in rats.Materials and methods: The rats were intragastrically (i.g.) given ZZDHD at doses of 1,2 and 4 g/kg (crude drug/body weight) once a day for seven days and treated with ANIT (75 mg/kg via i.g.) to cause liver injury at 12 h after the fifth administration. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma-glutamyltranspeptidase (gamma-GTP), total bilirubin (TBIL), direct bilirubin (DBIL) and total bile acid (TBA), as well as bile flow were measured at 48 h after ANIT treatment to evaluate the protective effect of ZZDHD. Moreover, the possible protective mechanisms were elucidated by assays of liver enzyme activities and component contents including malondialdehyde (MDA), myeloperoxidase (MPO), lipid peroxide (LPG), superoxide dismutase (SOD), glutathione peroxidase (GPx), and catalase (CAT). The biochemical observations were supplemented by histopathological examination. Ultra fast liquid chromatography-mass spectrometry (UFLC-MS) was used for the phytochemical analysis of ZZDHD.Results: The high dose (4 g/kg) and middle dose (2 g/kg) of ZZDHD exhibited significant and dose-dependent protective effect on ANIT-induced liver injury with cholestasis by reversing the changes in bile flow, the serum and hepatic enzymes, and histopathology of the liver tissue. Meanwhile, it was found that the low dose (1 g/kg) of ZZDHD did not improve the biochemical indexes except serum TBIL, DBIL and TBA, which showed little protective effect. Phytochemical analysis revealed the presence of sixteen compounds in ZZDHD.Conclusions: This study indicates that ZZDHD exerted a hepatoprotective effect on ANIT-induced liver injury with cholestasis in rats, and the mechanism of this activity is possibly related to its antioxidant properties. (C) 2015 Elsevier Ireland Ltd. All rights reserved.