The Protective Effect Of Madecassoside In Osteoarthritis And The Corresponding Mechanisms

Background and objective:Osteoarthritis(OA)is a chronic joint disease caused by the breakdown of subchondral bone and cartilage damage.Cartilage degeneration is the fundamental pathological process of OA.Inflammatory factors such as interleukin-1β play a central role in the progression of OA.Madecassoside(MA),atriterpenoid component derived from the herb gotu kola(Centella asiatica),exhibits various pharmacological exertions such as anti-oxidation characteristics and anti-inflammatory properties.In this study,the protective effects and potential mechanism of MA on OA were investigated.Methods:In vitro,rat knee chondrocytes were cultured and the osteoarthritis model of rat chondrocyte was established by interleukin-1β(IL-1β).The role of MA on chondrocyte viability was measured by CCK-8.The mRNA expressions of COX-2,iNOS,MMP-3 and MMP-13 in experimental group and control group were detected by polymerase chain reaction(qRT-PCR)at different concentrations of MA.The protein expression levels of COX-2,iNOS,MMP-3,MMP-13,collagen Ⅱ(Col2),Sox-9 and NF-KB p-p65/p65 were detected by western blotting.The protective effects of different concentrations of MA on chondrocyte were detected by Safranin 0 staining.In vivo experiments,the osteoarthritis of rats model was induced by destabilization of the medial meniscus(DMM),knee joint specimens were stained with safranin O and fast green and Mankin’s scores were then used to confirm the effects of MA on OA rat model.Results:MA significantly suppressed the IL-1β-induced expression of matrix metalloproteinase(MMP)-3,MMP-13,cyclooxygenase-2(COX-2),and inducible nitric oxide synthase(iNOS),and increased the IL-1β-induced downregulation of collagen II and sox9.Furthermore,madecassoside reduced IL-1β-induced p65 phosphorylation in rat chondrocytes.Additionally,in a rat OA model,madecassoside prevented cartilage degeneration with significantly lower Mankin’s score than the control group.ConclusionIn conclusion,the present study determined that MA suppresses chondrocyte inflammation via inhibiting NF-κB in vitro and attenuating cartilage degeneration in vivo.These data indicate that MA has therapeutic potential for OA treatment.