Alpha-Mangostin protects rat articular chondrocytes against IL-1β-induced inflammation and slows the progression of osteoarthritis in a rat model

Osteoarthritis (OA) is a joint disease characterized by inflammation and cartilage degradation. alpha-Mangostin (alpha-MG), which can be isolated from the fruit of the tropical evergreen tree Garcinia mangostana-L, is known to have anti-inflammatory properties. The aim of the study was to investigate the use of alpha-MG in the treatment of OA, using both rat chondrocytes and an OA rat model induced by destabilization of the medial meniscus (DMM). Rat chondrocytes were pretreated with alpha-MG (0, 1.25, 2.5, and 5.0 mu g/m1 for 24 h) prior to stimulation with interleukin-1 beta (IL-1 beta) (10 ng/ml for 24 h). Nitric oxide (NO) production was determined using the Griess method and prostaglandin E-2 (PGE(2)) was assessed using an enzyme-linked immunosorbent assay (ELISA). The expression of inducible nitric oxide synthase (INOS), cyclooxygenase-2 (COX-2), matrix metalloproteinase-3,-9, and -13 (MMP-3, MMP-9, and MMP-13), Collagen II, and Aggrecan were detected by both quantitative real-time PCR (qRT-PCR) and a western blot analysis. Nuclear factor-kappa B (NF-kappa B) signaling molecules were detected by western blot analysis. Detection of p65 nuclear translocation of NF-kappa B was examined using immunofluorescence staining. The OA rats received intraperitoneal injections of alpha-MG (10 mg/kg) or saline every other day. Hematoxylin and eosin and Safranin-O-Fast green staining were used to evaluate the severity of cartilage lesions up to 8 weeks following surgery. alpha-MG inhibited the production of NO and PGE(2). The elevated expression of INOS, COX-2, MMP-3, MMP-9, and MMP-13, and the degradation of Collagen II and Aggrecan, were reversed by alpha-MG in IL-1 beta-stimulated chondrocytes. In addition, IL-1 beta induced considerable phosphorylation of the NF-1(13 signaling pathway, which was inhibited by alpha-MG. Furthermore, the immunofluorescence staining demonstrated that alpha-MG could suppress IL-1 beta-induced p65 nuclear translocation. In vivo, cartilage treated with alpha-MG showed attenuated degeneration and had low Osteoarthritis Research Society International (OARSI) scores compared with the control group. Taken together, these results show that alpha-MG has potential therapeutic value in the treatment of OA.