The mechanism of Shenbing Decoction II against IgA nephropathy renal fibrosis revealed by UPLC-MS/MS, network pharmacology and experimental verification
Huaxi Liu,
Weijie Chen,
Chunyang Tian,
Yijian Deng,
Liangwo Xu,
Wenkun Ouyang,
Renjie Qiu,
Yanting You,
Pingping Jiang,
Lin Zhou,
Jingru Cheng,
Hiu Yee Kwan,
Xiaoshan Zhao,
Xiaomin Sun
Affiliations
Huaxi Liu
Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
Weijie Chen
Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
Chunyang Tian
Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
Yijian Deng
Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
Liangwo Xu
Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
Wenkun Ouyang
Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
Renjie Qiu
Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
Yanting You
Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
Pingping Jiang
Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China
Lin Zhou
Endocrinology Department, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China
Jingru Cheng
Department of Nephrology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, China
Hiu Yee Kwan
School of Chinese Medicine, Hong Kong Baptist University, Hong Kong, China
Xiaoshan Zhao
Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China; Corresponding author. Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Xiaomin Sun
Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, China; Corresponding author. Syndrome Laboratory of Integrated Chinese and Western Medicine, School of Chinese Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
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.
