Objective To investigate the effect of Naringin-induced autophagy on the expression of inflammatory factors in serum and chondrocytes in a rat model of osteoarthritis.Methods From November 2022 to December 2022,30 healthy Sprague-Dawley rats were randomly divided into a control group,a model group,and low-dose,medium-dose,and high-dose experimental groups,with six rats in each group.The model group and the low-dose,medium-dose,and high-dose experimental groups underwent resection of the medial meniscus and anterior cruciate ligament of the right knee to establish a rat model of osteoarthritis.The control group underwent a sham operation.During the modeling period,the low-dose,medium-dose,and high-dose experimental groups were administered Naringin at 25,50,and 100 mg/kg per day,respectively,while the control group and model group received an equal volume of 0.9%sodium chloride injection.After successful modeling,the Osteoarthritis Research Society International(OARSI)score and synovial score were used to assess the severity of osteoarthritis.The levels of interleukin(IL)-1β,IL-6,and tumor necrosis factor(TNF)-α in serum and chondrocytes were determined using an enzyme-linked immunosorbent assay.The mRNA expressions of IL-1β,IL-6,and TNF-α in chondrocytes were detected by reverse transcription-polymerase chain reaction.The changes in autophagy activity and the AKT/mTOR signaling pathway in chondrocytes were detected by western blotting.Results The OARSI scores for the control,model,and low-dose,medium-dose,and high-dose experimental groups were(0.80±0.75)points,(9.40±1.02)points,(8.20±1.33)points,(6.80±1.17)points,and(4.60±1.50)points,respectively.The synovial scores for these groups were(0.40±0.49)points,(3.80±0.75)points,(3.40±0.49)points,(2.20±0.98)points,and(1.60±0.80)points,respectively.The serum levels of IL-1β in these groups were(186.48±50.31)ng/L,(817.43±66.99)ng/L,(533.42±45.67)ng/L,(462.90±21.43)ng/L,and(396.64±24.66)ng/L,respectively.IL-6 levels in these groups were(448.25±89.42)ng/L,(1 762.49±171.95)ng/L,(1 517.08±83.87)ng/L,(1 019.78±103.32)ng/L,and(819.42±169.37)ng/L,respectively.The TNF-α levels in these groups were(419.67±60.99)ng/L,(1 287.40±184.68)ng/L,(948.73±87.82)ng/L,(860.55±102.21)ng/L,and(726.95±15.65)ng/L,respectively.The OARSI scores,synovial scores,serum levels of IL-1β,IL-6,and TNF-α,as well as the protein expressions of phosphorylated AKT(p-AKT)and phosphorylated mammalian target of rapamycin(p-mTOR)in chondrocytes,were significantly higher in the model group compared with the control group(all P<0.05).In contrast,the OARSI scores,synovial scores,serum levels of IL-1β,IL-6,and TNF-α,as well as the protein expressions of p62,p-Akt,and p-mTOR in chondrocytes,were significantly lower in the high-dose experimental group compared with the model group(all P<0.05).However,the protein expression of LC3-Ⅱ in chondrocytes was significantly higher in the high-dose experimental group compared with the model group(P<0.05).Conclusion Naringin can inhibit osteoarthritis in a rat model of osteoarthritis by inhibiting the Akt/mTOR signaling pathway,activating autophagy,and reducing the secretion of inflammatory factors.