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盐肤木果实通过调节氧化应激、细胞凋亡和胆汁酸转运来减轻异烟肼和利福平诱导的肝损伤。

Rhus chinensis Mill. fruits alleviate liver injury induced by isoniazid and rifampicin through regulating oxidative stress, apoptosis, and bile acid transport.

作者信息

Sun Yilin, Zhang Yuanyue, Ma Nan, Cai Shengbao

机构信息

Faculty of Food Science and Engineering, Kunming University of Science and Technology, Kunming, Yunnan Province, 650500, People's Republic of China.

出版信息

J Ethnopharmacol. 2023 Jun 28;310:116387. doi: 10.1016/j.jep.2023.116387. Epub 2023 Mar 21.

DOI:10.1016/j.jep.2023.116387
PMID:36948265
Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Rhus chinensis Mill. is a species of the genus Rhus belonging to the family Anacardiaceae. Its fruits used to treat/prevent liver related diseases (e.g., jaundice and hepatitis) in folk medicine. Otherwise, the effects and underlying mechanisms of the fruits on the prevention of isoniazid and rifampicin-caused liver injury have not been investigated.

AIM OF THE STUDY

To study the preventive effects and mechanisms of the Rhus chinensis Mill. fruits on isoniazid and rifampicin-caused liver injury.

MATERIALS AND METHODS

This experiment was based on rifampicin (75 mg/kg/day) and isoniazid (75 mg/kg/day)-induced liver damage model to explain the pharmacological effects of Rhus chinensis Mill. fruits. The prevention of the extract from Rhus chinensis Mill. fruits on isoniazid and rifampicin-caused liver injury were evaluated using biochemical parameters, histopathological analysis, and immunofluorescence technique. Apart from that, the potential molecular mechanisms were elucidated by analyzing the expression of such crucial proteins participated in oxidative stress, apoptosis, and bile acid transport.

RESULTS

The extract from Rhus chinensis Mill. fruits significantly reduced the levels of ALT, AST, TBIL, ALP and MDA. Besides, the extract, especially 800 mg/kg b.w., was remarkably decreased the content of TNF-α,IL-6 and IL-1β, restored the levels of GSH and SOD. The results of Western blot also presented that the extract could activate the Nrf2 protein pathway and inhibit the expression of CYP2E1 to reduce oxidative stress. Meanwhile, the extract significantly up-regulated the expressions of BSEP and Mrp2 to regulate the transport of bile acid, and alleviated the cellular apoptosis via adjusting the expression of Bax and Bcl-2 proteins.

CONCLUSIONS

Rhus chinensis Mill. fruits can prevent the liver injury induced by isoniazid and rifampicin in mice through adjusting the expressions of multiple proteins in oxidative stress, apoptosis, and bile acid transport pathways. This paper may provide scientific basis for the fruits as a Chinese medicine to prevent/cure liver injury.

摘要

民族药理学相关性

盐肤木是漆树科漆树属的一种植物。其果实在民间医学中用于治疗/预防肝脏相关疾病(如黄疸和肝炎)。否则,其果实对预防异烟肼和利福平引起的肝损伤的作用及潜在机制尚未得到研究。

研究目的

研究盐肤木果实对异烟肼和利福平引起的肝损伤的预防作用及机制。

材料与方法

本实验基于利福平(75mg/kg/天)和异烟肼(75mg/kg/天)诱导的肝损伤模型来解释盐肤木果实的药理作用。使用生化参数、组织病理学分析和免疫荧光技术评估盐肤木果实提取物对异烟肼和利福平引起的肝损伤的预防作用。除此之外,通过分析参与氧化应激、细胞凋亡和胆汁酸转运的关键蛋白的表达来阐明潜在的分子机制。

结果

盐肤木果实提取物显著降低了谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)、碱性磷酸酶(ALP)和丙二醛(MDA)的水平。此外,该提取物,尤其是800mg/kg体重,显著降低了肿瘤坏死因子-α(TNF-α)、白细胞介素-6(IL-6)和白细胞介素-1β(IL-1β)的含量,恢复了谷胱甘肽(GSH)和超氧化物歧化酶(SOD)的水平。蛋白质免疫印迹结果还表明,该提取物可激活核因子E2相关因子2(Nrf2)蛋白通路并抑制细胞色素P450 2E1(CYP2E1)的表达以减轻氧化应激。同时,该提取物显著上调了胆盐输出泵(BSEP)和多药耐药相关蛋白2(Mrp2)的表达以调节胆汁酸转运,并通过调节Bax和Bcl-2蛋白的表达减轻细胞凋亡。

结论

盐肤木果实可通过调节氧化应激、细胞凋亡和胆汁酸转运途径中多种蛋白的表达来预防小鼠由异烟肼和利福平诱导的肝损伤。本文可为该果实作为预防/治疗肝损伤的中药提供科学依据。

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