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. α-Mangostin (α-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 α-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 α-MG (0, 1.25, 2.5, and 5.0μg/ml for 24h) prior to stimulation with interleukin-1β (IL-1β) (10ng/ml for 24h). Nitric oxide (NO) production was determined using the Griess method and prostaglandin E2 (PGE2) 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-κB (NF-κB) signaling molecules were detected by western blot analysis. Detection of p65 nuclear translocation of NF-κB was examined using immunofluorescence staining. The OA rats received intraperitoneal injections of α-MG (10mg/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 8weeks following surgery. α-MG inhibited the production of NO and PGE2. 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 α-MG in IL-1β-stimulated chondrocytes. In addition, IL-1β induced considerable phosphorylation of the NF-kB signaling pathway, which was inhibited by α-MG. Furthermore, the immunofluorescence staining demonstrated that α-MG could suppress IL-1β-induced p65 nuclear translocation. In vivo, cartilage treated with α-MG showed attenuated degeneration and had low Osteoarthritis Research Society International (OARSI) scores compared with the control group. Taken together, these results show that α-MG has potential therapeutic value in the treatment of OA.
Pan T
，Wu D
，Cai N
，Chen R
，Shi X
，Li B
，Pan J
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Salvianolic acid B inhibits IL-1β-induced inflammatory cytokine production in human osteoarthritis chondrocytes and has a protective effect in a mouse osteoarthritis model.
Osteoarthritis (OA) is a chronic progressive disease that has complicated mechanisms that involve inflammation and cartilage degradation. In this study, we investigated the anti-inflammatory action of Salvianolic acid B (Sal B) in both human OA chondrocytes and a mouse OA model that was induced by destabilization of the medial meniscus. In vitro, chondrocytes were pretreated with Sal B (0, 25, 50, 100μM) for 2h, then incubated with IL-1β (10ng/mL) for 24h. NO production was determined by Griess method and PGE2 was assessed by ELISA. The expression of INOS, COX-2, MMP-13, ADAMTS-5 and NF-κB-related signaling molecules were tested by Western blotting. Immunofluorescence staining was used to detect P65 nuclear translocation. In vivo, the mouse OA model received intraperitoneal-injection of either Sal B (25mg/kg) or saline every other day. Hematoxylin and Eosin, as well as Safranin-O-Fast green staining, were utilized to evaluate the severity of cartilage lesions up to 8weeks following the surgery. Sal B inhibited the over-production of NO and PGE2, while the elevated expression of INOS, COX-2, MMP-13 and ADAMTS-5 were reversed by Sal B in IL-1β-induced chondrocytes. In addition, IL-1β significantly induced phosphorylation of NF-κB signaling, and this phosphorylation response was blocked by Sal B. Immunofluorescence staining demonstrated that Sal B could suppress IL-1β-induced p65 nuclear translocation. In vivo, the cartilage in Sal B-treated mice exhibited less cartilage degradation and lower OARSI scores. Taken together, Sal B possesses great potential value as a therapeutic agent for OA treatment.
Lou Y
，Wang C
，Zheng W
，Tang Q
，Chen Y
，Zhang X
，Guo X
，Wang J
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Butein inhibits IL-1β-induced inflammatory response in human osteoarthritis chondrocytes and slows the progression of osteoarthritis in mice.
Osteoarthritis (OA) is a progressive degenerative disease characterized by irreversible articular cartilage destruction. Butein, a polyphenolic compound isolated from the stem bark of cashews and Rhus verniciflua Stokes, has been reported to have anti-inflammatory effects. This study aimed to assess the effect of butein on human OA chondrocytes and mice OA models induced by destabilization of the medial meniscus (DMM). In vitro, human OA chondrocytes were pretreated with butein at 10, 50μM and subsequently stimulated with IL-1β (10ng/ml) for 24h. Production of NO, PGE2, TNF-α and IL-6 was evaluated by the Griess reaction and ELISAs. The mRNA expression of COX-2, iNOS, TNF-α, IL-6, MMP-1, MMP-3, MMP-13, ADAMTS-4, ADAMTS-5, COL-2 and SOX-9 were measured by real-time PCR. The protein expression of COX-2, iNOS, MMP-13, COL-2, SOX-9, p65 and IκB-α were detected by Western blot. P65 nuclear translocation was detected by immunofluorescence. In vivo, the severity of OA was determined by histological analysis. We found that butein significantly inhibited the IL-1β-induced production of NO and PGE2, expression of COX-2, iNOS, TNF-α, IL-6 and MMP-13, degradation of COL-2 and SOX-9 at mRNA and protein levels as well as MMP-1, MMP-3, ADAMTS-4 and ADAMTS-5 gene expression. Furthermore, butein dramatically suppressed IL-1β-stimulated IκB-α degradation and NF-kB p65 activation. In vivo, the cartilage in butein-treated mice exhibited less Safranin O loss, cartilage erosion and lower OARSI scores. Butein also reduced subchondral bone plate thickness and alleviated synovitis. Taken together, these findings indicate that butein may be a potential agent in the treatment of OA.
Zheng W
，Zhang H
，Jin Y
，Wang Q
，Chen L
，Feng Z
，Chen H
，Wu Y
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