Identification of the Main Chemical constituents and mechanism of Renshen Guben oral liquid against Renal Fibrosis

Chinese Medicine

Research

Junguo Ren¹  Juqin Peng¹  Junhong Zhang²  Yuewen Qin²  Tong Zhang²  Hong Jiang²  Ping Wang²  Xiaofang Deng²  Hong Chen²  Haiyu Xu³ 

[1] Beijing Key Laboratory of Pharmacology of Traditional Chinese Medicine, Institute of Basic Medical Sciences, Xiyuan Hospital of China Academy of Chinese Medical Sciences, 100091, Beijing, China;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700, Beijing, China;Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, 100700, Beijing, China;Key Laboratory for Research and Evaluation of Traditional Chinese Medicine, National Medical Products Administration, China Academy of Chinese Medical Sciences, 100700, Beijing, China;

关键词: RSGB;    UPLC-QTOF-MS/MS;    UUO model;    RNA sequencing;    “Constituents-targets-pathways” network;   

DOI  :  10.1186/s13020-023-00762-4

 received in 2023-02-16, accepted in 2023-05-01,  发布年份 2023

来源: Springer

【 摘 要 】

BackgroundRenal fibrosis is the late stage of many chronic kidney diseases (CKD). Clinically, there is almost no effective treatment for renal fibrosis except dialysis. Renshen Guben oral liquid (RSGB) is a Chinese patent medicine approved by National Medical Products Administration (NMPA), which is suitable for clinical patients with chronic nephritis. Currently, the chemical constituents of RSGB remains unclear, and its efficacy and mechanism on renal fibrosis have not been reported.MethodsIn our research, ultra-high performance liquid chromatography/quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS/MS) was employed to describe the chemical profile of RSGB, unilateral ureteral obstruction (UUO) model in mice was established to evaluate the beneficial effect of RSGB on renal fibrosis by biochemical indexes, HE and Masson staining. RNA sequencing and “constituents-targets-pathways” multi-dimensional network was established to mine the mechanisms of RSGB. Key targets were verified by quantitative real-time PCR (qRT-PCR) and western bolt (WB).ResultsA total of 201 constituents were identified or tentatively characterized, 15 of which were confirmed with standards. The number of triterpenes was the highest with 49, followed by phenols with 46. RSGB ameliorated the blood urea nitrogen (BUN) and serum creatinine (Scr) levels in serum, normalizing pathological structure of kidney tissue. RNA sequencing revealed that RSGB regulates 226 differential genes, which were involved in kidney development. According to the “constituents-targets-pathways” network, 26 key active constituents may mainly regulate the inflammatory immune system through 88 corresponding targets. qRT-PCR and WB results showed that RSGB inhibited the activation of the Tgfβ1/Smad2/3 pathway, Wnt4/β-Catenin pathway and NGFR/NF-κB pathway.ConclusionsOverall, our study, for the first time, characterized 201 chemical constituents in RSGB, and 26 of them were screened out to alleviates renal fibrosis mainly through Tgfβ1/Smad2/3 pathway, Wnt4/β-catenin pathway and NGFR/NF-κB pathway, which may provide a new research strategy for research on the mechanism of traditional Chinese Medicine.

【 授权许可】

CC BY   
© The Author(s) 2023

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