Alpha-Mangostin protects rat articular chondrocytes against IL-1β-induced inflammation and slows the progression of osteoarthritis in a rat model
Introduction
Osteoarthritis (OA) is the most common form of arthritis, causing physical limitations, disability, mental stress, and socioeconomic burden [1]. Research suggests that the disease is a breakdown of the cartilage repair process due to biomechanical and biochemical changes within the joint [2]. Oral or topical nonsteroidal anti-inflammatory drugs can relieve OA symptoms [3]. In addition, the use of hyaluronic acid, glucosamine or chondroitin can also play a role in relieving symptoms [4]. However, none of these drugs can delay the progression of OA. To date, the only effective method for the treatment of terminal OA is full joint replacement surgery. Given that few drugs can delay the progression of OA, new treatment strategies are urgently needed.
Many studies have shown that OA is related to age, obesity, trauma, and inflammation [5], [6]. Inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor (TNF)-α are key mediators in OA pathogenesis, which is closely related to cartilage matrix degradation [7]. Matrix metalloproteinases (MMPs) is another factor closely connected with the degradation of cartilage matrix and IL-1β can regulate its expression in the cell to a certain extent [8], [39]. Hence, inhibition of inflammation may be a valid method for the treatment of OA. Recently, research on the therapeutic effects of natural compounds on human diseases has aroused much attention. For example, anti-OA compounds, such as matrine, resveratrol, and sanguinarine have been widely used in such studies [8], [9], [10].
Fruit from the tropical evergreen tree Garcinia mangostana-L (mangosteen), found in Southeast Asia, has been used in traditional therapy in the treatment of skin infections, chronic wounds and dysentery for many years [11]. α-Mangostin (α-MG), the major xanthone purified from mangosteen, has been reported to have anti-inflammatory, anti-oxidant, and anti-bacterial effects [12], [13], [14], [15]. Although there have been many studies on α-MG, there have not been reports on α-MG as a therapeutic agent for OA. Therefore, in this study, the potential beneficial effects and the underlying mechanism of α-MG on the pathogenesis of OA were investigated both in an in vitro and in vivo experimental model.
Section snippets
Reagents
α-MG (purity ≥ 98%), Collagenase type II, and dimethylsulfoxide (DMSO) were obtained from Sigma Chemical Co. (St. Louis, MO, USA). α-MG was dissolved in DMSO as a 100 mg/ml stock solution and stored at 4 °C. Further dilution was done in cell culture medium. Cell-Counting Kit-8 (CCK-8) was purchased from Dojindo (Kumamoto, Japan). Fetal bovine serum (FBS), bovine serum albumin (BSA), Dulbecco's modified Eagle's medium (DMEM)/Ham's F 12 medium and 0.25% trypsin-ethylenediaminetetraacetic acid
The potential cytotoxicity of α-MG on rat chondrocytes
The potential cytotoxicity of α-MG on rat chondrocytes was determined by the CCK-8 assay. Cells were cultured with increasing concentrations of α-MG (0, 1.25, 2.5, 5.0, and 10 μg/ml) for 24 h and 48 h, respectively. According to Fig. 1A–B, cell viabilities were not influenced by α-MG at concentrations up to 5.0 μg/ml. Results were similar between the 24 h and 48 h group. Consequently, the concentrations of α-MG (1.25, 2.5, and 5.0 μg/ml) were used in subsequent experiments.
Effect of α-MG on IL-1β-induced production of NO and PGE2 in rat chondrocytes
Studies were conducted
Discussion
OA, which is characterized by progressive joint dysfunction and pain, is the most prevalent type of chronic degenerative joint disease [1], [19]. Although there are a variety of mechanisms involved in this disease, inflammation is one of the hallmark factors [20]. There are a number of drugs available for the treatment of OA, such as steroids and nonsteroidal anti-inflammatory drugs (NSAIDs), cartilage protective agents and intra-articular injections of glucocorticoids [4], [21]. However, these
Conclusion
In summary, we demonstrated the anti-inflammatory effects of α-MG in chondrocytes. These results showed that it is possible to protect chondrocytes by inhibiting the over-expression of inflammatory mediators, and synthesis of catabolic factors probably through blocked NF-κB activation. Both in vitro and in vivo studies confirmed the protective effects of α-MG in an OA rat model as well as cell culture. However, the complete molecular mechanism of α-MG in chondrocytes has not been fully
Conflict of interest
The authors declare that they have no conflict of interest.
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