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.