Stevioside attenuates osteoarthritis via regulating Nrf2/HO-1/ NF-ΚB pathway

Background: Osteoarthritis (OA) is a chronic disease that may cause articular cartilage degeneration, and synovial inflammation, resulting in considerable pain, poor quality of life, and functional limitations. Previous research has shown that ECM degradation and inflammation are involved in the progression of OA. Stevioside (STE), a naturally diterpenoid glycoside, is isolated from the Stevia rebaudiana (Bertoni), which has been exerted a variety of pharmacological activities, involving anti-inflammatory, anti-oxidative, and neuroprotective effects. However, STE's effects on OA and its mechanism still need further research. Methods: In the present study, we examined the anti-inflammatory effects of STE (STE) in both mouse chon-drocytes and OA model induced by destabilization of the medial meniscus (DMM). In vitro, the mouse chon-drocytes were treated with STE (0, 10, 20, 40 M, 24 h) after stimulated with IL-1 beta (10 ng/mL, 24 h). The expression of ant-inflammation-relative mediators iNOS and Cox-2 were detected by Western blot and RT-PCR. The catabolic factors (MMP-13, ADAMTS-4) and cartilage matrix constituent (Aggrecan, Collagen II) were measured by Western blot and Immunofluorescence staining. The Nrf2/HO-1/NF-Kappa B signaling molecules were detected by Western blot. In vivo, histological analysis was used to evaluate the severity of mouse OA models. Results: STE remarkably inhibited the IL-1 beta-induced expression of iNOS and Cox-2, generation of MMP-13, ADAMTS-4 and degradation of Aggrecan and Collagen II. Furthermore, we found that the chondroprotective effect of STE via Nrf2/HO-1/NF-Kappa B signaling pathway. In vivo, the cartilage treated with STE displayed attenu-ated degeneration, low OARIS scores compared with DMM group. In conclusion, we considered that STE might be a promising therapeutic agent for the treatment of OA in future. Conclusions: Our findings indicated that STE can ameliorate the development of OA via inhibiting the inflam-mation. The underlying mechanism may be related to the Nrf2/HO-1/NF-Kappa B signaling pathway. Moreover, the treatment of STE significantly relieves the progression in the mouse DMM model. All of the results demonstrated the therapeutic of STE in OA treatment. The translational potential of this article: This study demonstrates a more efficient and safe application of STE in treating osteoarthritis, provide a new concept for the cartilage targeted application of natural compounds.