Mechanism of Shenkang injection in treatment of renal fibrosis based on bioinformatics and in vitro experimental verification
- VernacularTitle:基于生物信息学和体外实验验证的肾康注射液治疗肾纤维化作用机制研究
- Author:
Gao-Quan MENG
1
,
2
;
Ming-Liang ZHANG
;
Xiao-Fei CHEN
;
Xiao-Yan WANG
;
Wei-Xia LI
;
Dai ZHANG
;
Lu JIANG
;
Ming-Ge LI
;
Xiao-Shuai ZHANG
;
Wei-Ting MENG
;
Bing HAN
;
Jin-Fa TANG
Author Information
- Keywords: Shenkang injection; renal fibrosis; bioin-formatics; drug repositioning; experimental verifica-tion; mechanism of action
- From: Chinese Pharmacological Bulletin 2024;40(10):1953-1962
- CountryChina
- Language:Chinese
- Abstract: Aim To explore the mechanism and mate-rial basis of Shenkang injection(SKI)in the treatment of renal fibrosis(RF)by bioinformatics and in vitro experiments.Methods The differentially expressed genes of RF were screened by GEO database.With the help of CMAP database,based on the similarity princi-ple of gene expression profile,the drugs that regulated RF were repositioned,and then the components of SKI potential treatment RF were screened by molecular fin-gerprint similarity analysis.At the same time,the core targets and pathways of SKI regulating RF were predic-ted based on network pharmacology.Finally,it was verified by molecular docking and cell experiments.Results Based on the GEO database,two RF-related data sets were screened,and CMAP was relocated to three common RF therapeutic drugs(saracatinib,da-satinib,pp-2).Molecular fingerprint similarity analysis showed that RF therapeutic drugs had high structural similarity with five SKI components such as salvianolic acid B and hydroxysafflor yellow A.Molecular docking results showed that salvianolic acid B,hydroxysafflor yellow A and other components had good binding abili-ty with MMP1 and MMP13,which were the core targets of SKI-regulated potential treatment of RF.Network pharmacology analysis suggested that the core targets of SKI were mainly enriched in signaling pathways such as Relaxin and AGE-RAGE.Cell experiments showed that SKI could significantly reduce the mRNA expres-sion levels of AGER,NFKB1,COL1A1,SERPINE1,VEGFC in AGE-RAGE signaling pathway and MMP1 and MMP13 in Relaxin signaling pathway in RF model cells,and significantly increase the mRNA expression level of RXFP1.Conclusions SKI can play a role in the treatment of RF by regulating Relaxin and AGE-RAGE signaling pathways,and its material basis may be salvianolic acid B,hydroxysafflor yellow A and other components.
