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亚节沙巴通过Keap1-Nrf2信号通路治疗肝纤维化的机制。

Mechanisms of Yajieshaba in the treatment of liver fibrosis through the Keap1-Nrf2 signaling pathway.

作者信息

Bai Yuanmei, Wu Haimei, Zheng Lijie, Xie Yuhuan, Liu Feifan, Wan Yan, Li Qiongchao, Guo Peixin

机构信息

College of Ethnic Medicine, Yunnan University of Chinese Medicine, Kunming, Yunnan, China.

The Second Affiliated Hospital of Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Front Pharmacol. 2023 May 9;14:1124015. doi: 10.3389/fphar.2023.1124015. eCollection 2023.

DOI:10.3389/fphar.2023.1124015
PMID:37229248
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10203482/
Abstract

Yajieshaba YJSB), a traditional Dai medicine formula containing botanical drugs, is commonly employed in Yunnan due to its significant therapeutic effects on liver protection. Consequently, to determine the efficacy of YJSB and the mechanism of action of Kelch-like ECH-associated protein 1 (Keap1)-nuclear factor erythroid 2-related factor 2 (Nrf2) pathway against liver fibrosis. We wanted to see if YJSB could treat CCl-induced liver fibrosis by regulating the Keap1-Nrf2 signaling pathway. YJSB significantly improved liver function biochemical indices, liver fibrosis quadruple, hydroxyproline (Hyp), and transforming growth factor-β1 (TGF-β1) levels. The staining results demonstrated that the degree of liver fibrosis was significantly reduced. YJSB reduced the content of malondialdehyde (MDA) and elevated the content of superoxide dismutase (SOD) in the liver, exhibiting antioxidant effects; meanwhile, it regulated the expression of Keap1-Nrf2 pathway protein, increased the expression of NAD(P)H: Quinone oxidoreductase (NQO1), Heme Oxygenase 1 (HO-1), Glutamate cysteine ligase modifier subunit (GCLM), and Glutamate cysteine ligase catalytic subunit (GCLC) expression in the liver decreased while Nrf2 expression increased. Fluorescence immunoassay studies demonstrated that YJSB promoted the trans-nuclearization of Nrf2. YJSB possesses anti-liver fibrosis pharmacological effects that improve liver function and effectively counteract CCl-induced liver fibrosis damage. The mechanism of action might be related to the regulation of protein expression of the Keap1-Nrf2 pathway, increasing the ability of the body to resist oxidative stress and reduce oxidative stress injury.

摘要

雅解沙巴（YJSB）是一种含有植物药的传统傣药配方，因其对肝脏保护具有显著治疗作用，在云南被广泛应用。因此，为了确定YJSB的疗效以及 Kelch样ECH相关蛋白1（Keap1）-核因子红细胞2相关因子2（Nrf2）通路抗肝纤维化的作用机制。我们想探究YJSB是否能通过调节Keap1-Nrf2信号通路治疗四氯化碳（CCl）诱导的肝纤维化。YJSB显著改善肝功能生化指标、肝纤维化四项、羟脯氨酸（Hyp）和转化生长因子-β1（TGF-β1）水平。染色结果表明肝纤维化程度显著降低。YJSB降低了肝脏中丙二醛（MDA）含量，提高了超氧化物歧化酶（SOD）含量，表现出抗氧化作用；同时，它调节Keap1-Nrf2通路蛋白的表达，增加肝脏中NAD（P）H：醌氧化还原酶（NQO1）、血红素加氧酶1（HO-1）、谷氨酸半胱氨酸连接酶修饰亚基（GCLM）和谷氨酸半胱氨酸连接酶催化亚基（GCLC）的表达，而Nrf2表达增加。荧光免疫分析研究表明YJSB促进了Nrf2的转核作用。YJSB具有抗肝纤维化药理作用，可改善肝功能并有效对抗CCl诱导的肝纤维化损伤。其作用机制可能与调节Keap1-Nrf2通路蛋白表达有关，增强机体抵抗氧化应激的能力，减少氧化应激损伤。

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