Protective Effect of Sinomenine on Cartilage Degradation and Chondrocytes Apoptosis

Abstract

Sinomenine (SIN), an alkaloid extracted from the stem of the Chinese medicinal plant sinomenium acutum, has been used for treating rheumatoid arthritis. But little is known whether SIN has a protective eŠect on osteoarthritis (OA). In this study, we investigated the protective eŠect of SIN on IL-1b-induced proteoglycan degradation and apoptosis in rabbit articular cartilage and chondrocytes. Treatment with 10 ng/ml IL-1b increased the level of glycosaminoglycan (GAG) released into the culture media, and up-regulated the activity and mRNA expression of matrix metalloproteinase 13 (MMP-13) and down-regulated the activity and mRNA expression of tissue inhibitor of metalloproteinase 1 (TIMP-1) in cartilage explants, as conˆrmed by the methods of GAG quantitation, MMP-13/TIMP-1 enzyme-linked immunosorbent assay (ELISA) and real-time quantitative RT-PCR. Treatment with 10 ng/ml IL-1b resulted in marked apoptosis in chondrocytes, as demonstrated by decreased cell viability, occurrence of DNA laddering and increased caspase-3 activity and annexin V binding of phosphatidylserine. However, simultaneous treatment with SIN (10, 50 or 250 mM) inhibited the GAG release and the activity and mRNA expression of MMP-13, and enhanced the activity and mRNA expression of TIMP-1 in a dose-dependent manner in cartilage explants. Furthermore, DNA fragment, caspase-3 activity and apoptosis rate were down-regulated, and cell viability was up-regulated dose-dependently in chondrocytes. Thus, SIN has the protective capacity to antagonize cartilage degradation and chondrocyte apoptosis, which suggest that SIN may act as an agent for pharmacological intervention in the progress of OA.

Saponin-rich fraction from Clematis chinensis Osbeck roots protects rabbit chondrocytes against nitric oxide-induced apoptosis via preventing mitochondria impairment and caspase-3 activation

“…Therefore, prevention of excessive apoptosis of chondrocytes is believed to be beneficial for OA management. Drugs that can ameliorate OA have been reported to show anti-apoptotic effects on chondrocytes, such as sinomenine (Ju et al 2010), ADAM15 (Böhm et al 2010) and amiloride (Rong et al 2011). Many triterpenoid saponin ingredients in traditional Chinese medicine have anti-apoptotic effects, such as astragaloside (Shang et al 2011), Panax notoginseng saponins , Ginsenoside-Rg2 (Zhang et al 2008).…”

Suppressive Effect of Sinomenine Combined with 5-Fluorouracil on Colon Carcinoma Cell Growth

“…It has previously been demonstrated that SIN exhibited a wide range of pharmacological actions including anti-inflammatory, anti-rheumatic, immunosuppressive, analgesic and antiarrhythmic effects (Shu et al, 2007;Teng et al, 2012;Song et al, 2013). And there are many other researches indicate that SIN has many pharmacological characters such as inducing apoptosis and anti-angiogenesis effect what has been treated as means of treating colon carcinoma (Kok et al, 2005;Ju et al, 2010;Chen et al, 2011).…”

“…Many reports show that SIN has the potent of inhibiting proliferation and inducing apoptosis on chondrocytes (Ju et al, 2010), CD4+ T cells (Shu et al, 2007), monocytes (Jiang et al, 2007) and tumor cells (Jiang et al, 2010). But the specific mechanism about how SIN inducing apoptosis has not been researched clearly.…”

Effect of semen sojae germinatum on experimental osteoarthritis in the rabbit knee

“…Many researches have demonstrated that enzymatic cleavage by MMPs together with pro-inflammatory cytokines plays critical roles in the initiation and progression of cartilage destruction (Ju et al, 2010). The results of this study demonstrated that the contents of PGE2 , NO, TNF-α, IL-6 and IL-1β in synovia and expressions of MMP-3, MMP-13 in cartilage were elevated in OA model group, whereas the elevation of PGE2 , NO, TNF-α, IL-6, IL-1β, MMP-3 and MMP-13 levels were significantly suppressed in SSG groups.…”