Potential molecular mechanism of Yishen capsule in the treatment of diabetic nephropathy based on network pharmacology and molecular docking technology
Abstract Background : Using network pharmacology and molecular docking technology to explore the mechanism of Yishen capsules in the treatment of diabetic nephropathy. Methods: Active components of Yishen Capsules were obtained using database such as TCMSP and TCMID, and diabetic nephropathy targets were obtained from databases such as Gencards, OMIM, DisGeNET. A network of "Yishen Capsule Components-Diabetic Nephropathy Targets-Pathways" was constructed by analyzing data above to screening out core targets for molecular docking verification. Finally, a rat model of diabetic nephropathy was generated, and renal tubular epithelial cells were extracted and cultured under high glucose conditions. Based on these experimental models, the key signal pathway target protein genes screened by network pharmacology were verified both in vitro and in vivo. Results: The main active components of Yishen Capsule in the treatment of diabetic nephropathy include quercetin, kaempferol, gallic acid, astragaloside IV and so on. Some key targets (such as AR, AKT1, TP53, ESR1, JUN) and important signal pathways (such as AGE-RAGE signal pathway, HIF-1 signal pathway and JAK-STAT signal pathway) were included in the treatment of diabetic nephropathy of Yishen Capsule. Molecular docking assay showed that most of the targets have good binding activity with the components of Yishen Capsules. Based on the results of network pharmacology, key target proteins in HIF-1α and JAK2/STAT3 signaling pathways were selected for experimental verification. Results presented that HIF-1α, JAK2, STAT3, TGF-β and MCP were increased under high glucose environment. With the treatment of Yishen Capsule, the expression of HIF-1α further increased, while the expression of JAK2, STAT3, MCP-1 and TGF-β were decreased. Conclusions : This study revealed the mechanism of Yishen Capsules in the treatment of diabetic nephropathy, which possesses the characteristics of multi-component, multi-target, and multi-pathway. Further experiments confirmed that Yishen Capsules interfered with HIF-1α and JAK/STAT signaling pathways to reduce inflammation and fibrosis damage in the kidney tissue of rats with diabetic nephropathy. Key Words: Diabetic Nephropathy(DN); Network pharmacology; Molecular docking;HIF-1α; JAK/STAT