Exploration on the mechanism of Juanbi Capsules in the treatment of knee osteoarthritis based on ferroptosis mediated by Nrf2/GPX4 signaling pathway
10.3760/cma.j.cn115398-20250312-00183
- VernacularTitle:基于Nrf2/GPX4信号通路介导的铁死亡探讨蠲痹胶囊干预膝骨关节炎的作用机制
- Author:
Mengyuan LI
1
;
Li WANG
;
Puwei YUAN
;
Wulin KANG
;
Xun LI
;
Panxin MA
Author Information
1. 陕西中医药大学医学技术学院，咸阳 712046
- Keywords:
Osteoarthritis, knee;
Juanbi Capsule;
Nuclear factor erythroid 2-related factor 2;
Ferroptosis;
Glutathione peroxidase 4;
Rats
- From:
International Journal of Traditional Chinese Medicine
2025;47(11):1561-1567
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the mechanism of Juanbi Capsules in the intervention of knee osteoarthritis by inhibiting lipid peroxidation and chondrocyte ferroptosis through activating nuclear factor E2 related factor (Nrf2)/glutathione peroxidase 4 (GPx4) signaling pathway.Methods:Totally 45 rats were randomly divided into blank group, model group and Juanbi Capsules low-, medium- and high-dosage groups, with 9 rats in each group. Except the blank group, the other groups were injected with sodium monoiodoacetate (MIA) to establish knee osteoarthritis model. From the third week of modeling, rats in Juanbi Capsules low-, medium- and high-dosage groups were gavaged with 108.05, 216.09, and 432.18 mg/kg of Juanbi Capsules suspension, and rats in the blank group and model group were gavaged with equal volume of normal saline, once a day, for 28 consecutive days. HE and safranine fast green staining were used to observe the pathological changes of cartilage tissue, and Mankin's score was performed; the levels of MDA, Fe 2+, glutathione (GSH) in articular cartilage were detected by biochemical kit; Western blot was used to detect the protein expressions of SLC7A11, GPx4, acsll4 and Nrf2 in rat articular cartilage. Results:Compared with the model group, the Mankin's score was significantly lower in the Juanbi Capsules middle- and high-dosage groups ( P<0.01); the MDA level decreased in Juanbi Capsules low-, medium- and high-dosage groups ( P<0.01), GSH level increased ( P<0.01), and and Fe 2+ level decreased Juanbi Capsules middle- and high-dosage groups ( P<0.01, P<0.05); the protein expressions of Nrf2, SLC7A11 and GPx4 in cartilage tissue of Juanbi Capsules middle- and high-dosage groups increased ( P<0.01 or P<0.05), the expression of ACSl4 protein decreased ( P<0.01 or P<0.05), and SLC7A11 protein expression increased in Juanbi Capsules low-dosage group ( P<0.05). Conclusion:Juanbi Capsule may inhibit the ferroptosis of rat articular cartilage by activating the Nrf2/GPX4 signaling pathway.
