Study on the Mechanism of Cycloastragenol in Treating Renal Fibrosis Based on Network Pharmacology
Objective To investigate the target and mechanism of cycloastragenol in treating renal fibrosis.Methods The core target of cycloastragenol targeted renal fibrosis was predicted by network pharmacology,and its GO enrichment and KEGG pathway were analyzed.Molecular docking technology was used to verify the binding properties of cycloastragenol to the core target.A mouse model of renal fibrosis with unilateral ureteral ligation was established,and continuous intragastacal administration was terminated after 7 d,14 d and 21 d,respectively.The renal body ratio,BUN and CRE levels were detected.The histopathological changes of kidney were observed by HE and Masson staining.The expression levels of TGF-β1,α-SMA,MMP3 and MMP2 in renal tissues were determined by qRT-PCR and Western Blotting.Results Network pharmacology and molecular docking results showed that 8 targets of renal fibrosis were successfully docked with cycloastragenol,among which MMP3 and MMP2 had the best binding energy.The results of animal experiments showed that cycloastragenol could effectively improve the deposition of renal collagen fiber and reduce the expression of TGF-β1,α-SMA,MMP3 and MMP2 in mice with renal fibrosis,with statistical significance(P＜0.05).With the increase of dosage and time of administration,the positive expression of each index showed a decreasing trend.Conclusion Cycloastragenol may act on targets such as MMP3 and MMP2,mediated Rap1 signaling pathway,IL-17 signaling pathway,and Progesterone-mediated oocyte maturation,Lipid and atherosclerosis pathways play a role in the treatment of renal fibrosis.
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