Objective:To study the mechanism of kaempferol in the intervention of knee osteoarthritis(KOA)in mice by inhibiting cartilage apoptosis.Methods:Firstly,the target genes of kaempferol were retrieved via TCMSP,and the genes related to KOA were obtained by GeneCards,OMIM,PharmGKB,TTD,and Drugbank databases.Then GO enrichment analysis and KEGG signaling pathway analysis were also performed.Subsequently,18 male C57 mice were randomly divided into the sham operation group,the model group,and the kaempferol group(50 mg/kg).Except for the sham operation group,the KOA mouse model was induced by destabilization of medial meniscus surgery.The sham operation group and model group were given the same amount of normal saline daily for 8 weeks while the kaempferol group was given 50 mg/kg kaempferol intragastrically.Results:A total of 63 targets of kaempferol were found that included 35 common target genes with KOA.GO and KEGG analyses showed that biological processes such as extrinsic apoptotic signaling pathway and response to oxidative stress,as well as signaling pathways such as cell apoptosis and regulation of TNF were closely related to common target genes.Molecular docking results also showed kaempferol has good binding properties with predicted targets Bcl-2,BAX,and CASP3.Compared with the model group,the pathological changes of cartilage in the kaempferol group were significantly reduced,OARSI scores were significantly decreased(P<0.001),and cartilage area was increased(P<0.01).In addition,Western blot analysis showed that kaempferol significantly decreased the protein expression of BAX and CASP3(P<0.01,P<0.05),and increased the protein expression of BCL-2(P<0.05).Conclusion:The treatment of KOA with kaempferol has the characteristics of multi-target and multi-pathway,and the mechanism may be related to the regulation of key genes such as Bcl-2,BAX,and CASP3 to inhibit cartilage apoptosis.
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