Yishen Qingli Heluo Granule in the Treatment of Chronic Kidney Disease: Network Pharmacology Analysis and Experimental Validation

Abstract

Background Chronic kidney disease (CKD) is considered a global public health problem with high morbidity and mortality. Yishen Qingli Heluo granule (YQHG) is representative traditional Chinese medicine (TCM) remedy for clinical treatment of CKD. This study aims to explore the mechanism of YQHG on CKD through network pharmacology and experimental validation. Methods Traditional Chinese Medicine Systems Pharmacology (TCMSP) database and wide-scale literature mining were applied to screen active compounds of YQHG. Multiple bioinformatic tools and online databases were applied by us to obtain relevant targets of YQHG and CKD. The intersection targets between YQHG and CKD were considered as candidate targets. The compound-target, herb-candidate target and protein–protein interaction networks were constructed and visualized for topological analyses. GO and KEGG enrichment analyses were conducted to determine the biological processes and signaling pathways. Molecular docking was used to verify the reliability of network pharmacology. Finally, pharmacological evaluation was performed to explore the mechanism of YQHG against CKD on a 5/6 nephrectomy model. Results Seventy-nine candidate targets, ten core biological processes and one key signaling pathway (p53) were screened. PTGS2 was identified as a key target based on H-CT network. The molecular docking showed that Quercetin, Kaempferol, Luteolin were three key compounds with the best binding activity. In addition, IL6 and Quercetin could form a stable complex with high binding affinity (−7.29 kcal/mol). In vivo experiment revealed that YQHG improved kidney function and fibrosis in 5/6 nephrectomized rats. Moreover, the decreased expression of PTGS2, IL6, and the increased expression of p53 were observed in kidney tissue. Notably, the gut microbiota of rats treated with YQHG was reshaped, which was characterized by a reduced ratio of Firmicutes/Bacteroidota. Conclusion Our results predicted and verified the potential targets of YQHG on CKD from a holistic perspective, and provided valuable direction for the further research of YQHG.

Association between consumption of flavonol and its subclasses and chronic kidney disease in US adults: an analysis based on National Health and Nutrition Examination Survey data from 2007–2008, 2009–2010, and 2017–2018

“…Research on the relationship between kaempferol, isorhamnetin, myricetin, and CKD is sparse. Some network-based pharmacological studies suggest that kaempferol and myricetin may have protective effects on renal function, offering new perspectives for the development of new CKD treatment ( 48 , 49 ). However, this study did not find a correlation between the intake of myricetin or kaempferol and the incidence of CKD, indicating a need for further research to determine the causal relationship between the consumption of kaempferol or myricetin and CKD.…”

“…However, this study did not find a correlation between the intake of myricetin or kaempferol and the incidence of CKD, indicating a need for further research to determine the causal relationship between the consumption of kaempferol or myricetin and CKD. Regarding isorhamnetin, some studies found that isorhamnetin can improve TGF-β1-induced glycolysis and renal fibrosis ( 48 , 49 ). This study found an association between high isorhamnetin intake and a lower incidence of CKD, suggesting that isorhamnetin may benefit CKD patients.…”

Network Pharmacology Analysis and Machine-Learning Models Confirmed the Ability of YiShen HuoXue Decoction to Alleviate Renal Fibrosis by Inhibiting Pyroptosis

“… 91 In CKD, PTGS2 is involved in the regulation of inflammatory factors accumulation in target organs, which consequently induces tissue fibrosis. 92 Although AR has been studied quite extensively in the field of cancer, there are few reports of its effects on RF and hence, no experimental validation was performed. In accordance with these previous reports, our molecular docking and MD simulations demonstrated that IL-1β, IL-6, TNF-α, PTGS2, and AR are were involved in therapeutic mechanism of YSHXD in RF.…”

Traditional Chinese Medicine: An Exogenous Regulator of Crosstalk between the Gut Microbial Ecosystem and CKD

“… Details of Yishen Qingli Heluo Granule (YQHG) [ 12 ]: (1) the genus; (2) parts used; (3) dose used (g). …”

“…Bidirectionally, TCM herbs or herbal extracts can also remodel the diversity of gut microbiota to alleviate related diseases [ 11 ]. Several recent studies have determined that TCM can significantly influence the progression of CKD [ 12 , 13 ]. However, there is still a lack of a comprehensive summary of the effects and mechanisms of TCM on CKD from the perspective of microecology.…”