The mechanism of Shenbing Decoction II against IgA nephropathy renal fibrosis revealed by UPLC-MS/MS, network pharmacology and experimental verification.
The mechanism of Shenbing Decoction II against IgA nephropathy renal fibrosis revealed by UPLC-MS/MS, network pharmacology and experimental verification.
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DOI：
10.1016/j.heliyon.2023.e21997
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发表时间：
2023-11
期刊：
影响因子：
4
通讯作者：
Sun, Xiaomin
中科院分区：
文献类型：
--
作者：
Liu, Huaxi;Chen, Weijie;Tian, Chunyang;Deng, Yijian;Xu, Liangwo;Ouyang, Wenkun;Qiu, Renjie;You, Yanting;Jiang, Pingping;Zhou, Lin;Cheng, Jingru;Kwan, Hiu Yee;Zhao, Xiaoshan;Sun, Xiaomin
关键词：
伊加肾病（IgAN）是一个主要的和日益增长的公共卫生问题。肾纤维化在IgAN的进展中起着至关重要的作用。本研究采用超高效液相色谱-串联质谱法（UPLC-MS/MS）、网络药理学和实验验证等方法，探讨肾衰汤Ⅱ号治疗IgAN肾纤维化的作用机制。我们首先采用UPLC-MS/MS方法探索SBDII的主要化合物，然后采用网络药理学方法预测SBDII治疗IgAN肾纤维化的作用靶点和关键通路。其次，采用牛血清白蛋白（BSA）、脂多糖（LPS）和四氯化碳（CCL 4）诱导大鼠IgAN，检测生化指标、肾组织病理学和肾纤维化相关指标。同时，也验证了网络药理学预测的部分结果。通过UPLC-MS/MS共鉴定出105个化合物。网络药理学结果表明，活性化合物金合欢素、eupatilin和高良姜素可能通过靶向肿瘤蛋白p53（TP 53）和调节磷脂酰肌醇3-激酶（PI 3 K）-Akt激酶（Akt）信号通路介导SBDII治疗IgA肾病的作用。动物实验表明，SBDII不仅能显著改善IgAN大鼠肾功能和纤维化，而且能显著下调p53、p-PI 3 K和p-Akt的表达。该UPLC-MS/MS、网络药理学和实验研究突出了TP 53作为靶点和PI 3 K-Akt信号通路是SBDII参与IgAN肾纤维化治疗的潜在机制。Acacetin、eupatilin和galangin可能是SBDII的活性成分，这些结果可能为进一步研究IgAN肾纤维化的治疗提供有价值的指导。
IgA nephropathy (IgAN) is a major and growing public health problem. Renal fibrosis plays a vital role in the progression of IgAN. This study is to investigate the mechanisms of action underlying the therapeutic effects of Shenbing Decoction II (SBDII) in IgAN renal fibrosis treatment based on ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), network pharmacology and experimental verification. We first used UPLC-MS/MS to explore the main compounds of SBDII, and then used network pharmacology to predict the targets and key pathways of SBDII in the treatment of IgAN renal fibrosis. Next, bovine serum albumin (BSA), lipopolysaccharide (LPS), and carbon tetrachloride (CCL4) were used to induce IgAN in rats, and then biochemical indicators, renal tissue pathology, and renal fibrosis-related indicators were examined. At the same time, part of the results predicted by network pharmacology were also verified. A total of 105 compounds were identified in SBDII by UPLC-MS/MS. Network pharmacology results showed that the active compounds such as acacetin, eupatilin, and galangin may mediate the therapeutic effects of SBDII in treating IgAN by targeting tumor protein p53 (TP53) and regulating phosphatidylinositol 3-kinase (PI3K)-Akt kinase (Akt) signaling pathway. Animal experiments showed that SBDII not only significantly improved renal function and fibrosis in IgAN rats, but also significantly downregulated the expressions of p53, p-PI3K and p-Akt. This UPLC-MS/MS, network pharmacological and experimental study highlights that the TP53 as a target, and PI3K-Akt signaling pathway are the potential mechanism by which SBDII is involved in IgAN renal fibrosis treatment. Acacetin, eupatilin, and galangin are probable active compounds in SBDII, these results might provide valuable guidance for further studies of IgAN renal fibrosis treatment.
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影响因子：
3.7
作者：
Moriyama T;Tanaka K;Iwasaki C;Oshima Y;Ochi A;Kataoka H;Itabashi M;Takei T;Uchida K;Nitta K
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影响因子：
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DOI：
10.1152/ajprenal.00393.2016
发表时间：
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影响因子：
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作者：
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影响因子：
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