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Abstract Objective To study the mechanism of taraxasterol in the treatment of knee osteoarthritis(KOA)in rats.Methods KOA rats model was prepared by injecting 0.2 mL of 4% papain solution +0.03 mmol/L cysteine into the joint cavity.The taraxasterol 2.5 mg/kg(low-dose group)，5 mg/kg(medium-dose group)，10mg/kg(high-dose group)and saline(model group)were administered by gavage，respectively.The sham operation group was prepared by injecting 0.2 mL of normal saline into the joint cavity and gavage with normal saline.4 weeks after administration，the serum levels of tumor necrosis factor-α(TNF-α)，interleukin-1 β(IL-1β)，IL-6，matrix metalloproteinase-1(MMP-1)，MMP-3 and cysteine aspartic acid protease-1(Capase-1)in were determined by enzymelinked immunosorption.The expression levels of microRNA(miRNA)-140 and miRNA-146a in articular cartilage tissue were determined by -time PCR(RT-qPCR).The protein expression levels of inhibitor of NF-κB(IκB)，inhibitor κB kinase β(IKKβ)，nuclear factor-κB(NF-κB)，transforming growth factor-βactivated kinase 1(TAK1)，NOD-like receptors 3(NLRP3)，apoptosis-associated speck-like protein containing CARD(ASC)in articular cartilage tissue were determined by Western blot.The pathological observation of articular cartilage was conducted.Results Compared with the sham operation group，the serum levels of TNF-α，IL-1β，IL-6，MMP-1，MMP-3，Capase-1 and the protein expression levels of IκB，IKKβ，NFκB，TAK1，NLRP3，ASC and Mankin score in articular cartilage tissue in high-dose，medium-dose，low-dose group and model group was significantly increased(P＜0.05)，the expression levels of miRNA-140 and miRNA-146a in articular cartilage were significantly decreased(P＜0.05).Compared with the model group，the serum levels of TNF-α，IL-1β，IL-6，MMP-1，MMP-3，Capase-1 and the protein expression levels of IκB，IKKβ，NF-κB，TAK1，NLRP3，ASC and Mankin score in articular cartilage tissue in high-dose，medium-dose and low-dose group was significantly decreased(P＜0.05)，it decreased significantly with the increase of dose(P＜0.05)，the expression levels of miRNA-140 and miRNA146a in articular cartilage were significantly increasedd(P＜0.05)，it increased significantly with the increase of dose(P＜0.05).Conclusion Taraxasterol has a protective effect on KOA rats，alleviate the pathological changes of articular cartilage tissue，and it was dose-dependent.The mechanism might be related to inflammation inhibition，up-regulation of miRNA expression and activation blocked of TAK1/NF-κB，NLRP3 signaling pathway.
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