Mechanism of action of Jiuwei Jianbu Decoction in the treatment of knee osteoarthritis based on network pharmacology and experiments
Objective It is to predict and verify the potential mechanism of action of Jiuwei Jianbu Decoction in the treatment of knee osteoarthritis based on network pharmacology and animal experiments.Methods①The database was used to screen the active chemical components of each herb of Jiuwei Jianbu Decoction and the targets of knee osteoarthritis,and GO and KEGG enrichment analysis and molecular docking were carried out for the targets,so as to initially explore the po-tential targets and mechanisms of Jiuwei Jianbu Decoction in the treatment of knee osteoarthritis.②Forty male SD rats were randomly divided into blank group,model group and low,medium and high dose group of Jiuwei Jianbu Decoction,with 8 rats in each group.The rats of all groups except for the blank group were injected with sodium iodoacetate into the joint cav-ity to establish models of knee osteoarthritis.After 2 weeks of modeling,the low,medium and high dose group of Jiuwei Jianbu Decoction were given 7.78 g/(kg·d),15.56 g/(kg·d),and 31.12 g/(kg·d)of Jiuwei Jianbu Decoction by gavage,respectively,and the blank and model groups were given equal volumes of saline by gavage,all continuously trea-ted for 2 weeks.The histopathological morphology of knee joint cartilage was observed by HE staining,the serum levels of interleukin-1β(IL-1β),interleukin-6(IL-6),interleukin-8(IL-8),and tumor necrosis factor-α(TNF-α)were detected by ELISA,and the expressions of phosphorylated phosphatidylinositol 3-kinase(p-PI3K),phosphorylated protein kinase B(p-Akt),and phosphorylated rapamycin target protein(p-mTOR)in cartilage tissues were detected by Western blot to ver-ify the network pharmacology results.Results ①There were 123 active ingredients in Jiuwei Jianbu Decoction,with 248 common targets,including apoptosis pathway,PI3K/Akt signaling pathway,etc;the molecular docking showed that the core targets and their corresponding active ingredients had good stability.②The layering of the cartilage surface of knee joint was not clear with reduced number of chondrocytes in the rats of the model group;the levels of serum IL-1β,IL-6,IL-8,TNF-α and the relative expressions of p-PI3K,p-Akt and p-mTOR proteins in the cartilage tissues were significantly higher than those in the blank group(all P<0.05).The layering of the cartilage surface of knee joint was clearer in the rats of each group of Jiuwei Jianbu decoction,and the number of chondrocytes was higher than that of the model group;the levels of serum IL-1β,IL-6,IL-8,TNF-α and the relative expressions of p-PI3K,p-Akt and p-mTOR proteins in the carti-lage tissues were significantly lower than those of the model group(all P<0.05),and the above indexes were decreased more significantly with the increase of the dosage of Jiuwei Jianbu decoction(all P<0.05).Conclusion Jiuwei Jianbu De-coction may regulate the expressions of IL6,TNF,IL1B,AKT1 and other targets through regulating PI3K/Akt signaling pathway and apoptosis pathway,in order to alleviate the inflammatory response in the joints and slow down the degeneration of articular cartilage.
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