TY - JOUR
T1 - The mechanism of Shenbing Decoction II against IgA nephropathy renal fibrosis revealed by UPLC-MS/MS, network pharmacology and experimental verification
AU - Liu, Huaxi
AU - Chen, Weijie
AU - Tian, Chunyang
AU - Deng, Yijian
AU - Xu, Liangwo
AU - Ouyang, Wenkun
AU - Qiu, Renjie
AU - You, Yanting
AU - Jiang, Pingping
AU - Zhou, Lin
AU - Cheng, Jingru
AU - Kwan, Hiu Yee
AU - Zhao, Xiaoshan
AU - Sun, Xiaomin
N1 - Funding Information:
This work was supported by the National Natural Science Foundation of China, China (81673960, 81774212, 81973666), the Natural Science Foundation of Guangdong Province, China (2018030310451, 2018A0303130320, 2019A1515010400, 2019A1515010816), and the Innovation Team and Talents Cultivation Program of the National Administration of Traditional Chinese Medicine, China. (ZYYCXTD-C-202001).
Publisher Copyright:
© 2023 The Authors.
PY - 2023/11
Y1 - 2023/11
N2 - Background: 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.Method: 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.Result: 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.Conclusion: 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.
AB - Background: 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.Method: 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.Result: 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.Conclusion: 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.
KW - IgA nephropathy
KW - Network pharmacology
KW - PI3K-Akt signaling pathway
KW - Renal fibrosis
KW - Shenbing Decoction II
KW - TP53
UR - http://www.scopus.com/inward/record.url?scp=85176430366&partnerID=8YFLogxK
U2 - 10.1016/j.heliyon.2023.e21997
DO - 10.1016/j.heliyon.2023.e21997
M3 - Journal article
AN - SCOPUS:85176430366
SN - 2405-8440
VL - 9
JO - Heliyon
JF - Heliyon
IS - 11
M1 - e21997
ER -
