Dengying Wu1, Xingyu Zhu2, Xiaodiao Kang1, Huasong Huang2, Jiale Yu2, Jun Pan3, Xutong Zhang4. 1. Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109, Xueyuanxi Road, 325027 Wenzhou, China. 2. The Second Clinical Medical School of the Wenzhou Medical University, 82, Xueyuanxi road, 325027 Wenzhou, China. 3. Department of Orthopaedic Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109, Xueyuanxi Road, 325027 Wenzhou, China. Electronic address: panjun@wmu.edu.cn. 4. Department of Anesthesiology, The Second Affiliated Hospital of Wen Zhou Medical University, 109, Xueyuanxi Road, 325027 Wenzhou, China. Electronic address: zhangxutong@wmu.edu.cn.
Abstract
BACKGROUND: Osteoarthritis (OA) is a type of degenerative joint disease affecting millions of individuals worldwide. However, there are currently no great inflammatory treatments available for it. Sophocarpine (SPC), one of the key bioactive compounds derived from Sophora flavescens, has shown remarkable anti-inflammatory effects. METHODS: In this study, we evaluated the effect of SPC on preventing the progression of OA and investigated its molecular target involved. In brief, rat chondrocytes were pretreated with SPC and subsequently stimulated with IL-1β. We found that SPC reduced the production of pro-inflammatory cytokines, such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). SPC also inhibited the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at both the gene and protein level. Moreover, SPC promoted the expression of anabolic factors Sox-9 and aggrecan, while inhibiting the expression of catabolic factors, such as matrix metalloproteinases 13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) in rat chondrocytes. Mechanistically, we found that SPC inhibited nuclear factor kappa B (NF-κB) via the phosphatidylinositol 3 kinase (PI3K)/AKT pathway. The beneficial effects of SPC were also observed in vivo using a rat OA model. CONCLUSIONS: Our findings indicate that SPC may be a potential novel therapeutic in the treatment of OA.
BACKGROUND:Osteoarthritis (OA) is a type of degenerative joint disease affecting millions of individuals worldwide. However, there are currently no great inflammatory treatments available for it. Sophocarpine (SPC), one of the key bioactive compounds derived from Sophora flavescens, has shown remarkable anti-inflammatory effects. METHODS: In this study, we evaluated the effect of SPC on preventing the progression of OA and investigated its molecular target involved. In brief, rat chondrocytes were pretreated with SPC and subsequently stimulated with IL-1β. We found that SPC reduced the production of pro-inflammatory cytokines, such as nitric oxide (NO), prostaglandin E2 (PGE2), tumor necrosis factor alpha (TNF-α), and interleukin-6 (IL-6). SPC also inhibited the expression of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (iNOS) at both the gene and protein level. Moreover, SPC promoted the expression of anabolic factors Sox-9 and aggrecan, while inhibiting the expression of catabolic factors, such as matrix metalloproteinases 13 (MMP-13) and thrombospondin motifs 5 (ADAMTS-5) in rat chondrocytes. Mechanistically, we found that SPC inhibited nuclear factor kappa B (NF-κB) via the phosphatidylinositol 3 kinase (PI3K)/AKT pathway. The beneficial effects of SPC were also observed in vivo using a rat OA model. CONCLUSIONS: Our findings indicate that SPC may be a potential novel therapeutic in the treatment of OA.