Mangosteen ethanol extract alleviated the severity of collagen-induced arthritis in rats and produced synergistic effects with methotrexate

Context:Garcinia mangostana Linn. (Guttiferae) pericarp is used as a traditional medicine in South Asia to treat inflammatory diseases. Objective: This study investigates therapeutic effects of G. mangostana pericarp ethanol extract (MAN) on collagen-induced arthritis (CIA) and interactions with methotrexate in vivo. Materials and methods: Male Sprague-Dawley rats with CIA were treated with MAN (0.5 g/kg/day), methotrexate (0.5 mg/kg, bw) or combination of both for 36 days, respectively (n = 8/group). Another eight healthy and CIA rats served as normal and model control, respectively. Therapeutic effects were evaluated based on paw edema and arthritis score during the experiment and serological markers at the end of the study period. Histological and radiological examinations were used to assess joint destructions. The immune status was investigated by immunohistochemistry and flow cytometry. Results: All treatments decreased the arthritis score and paw inflammation in CIA rats. Combination regimen significantly reduced anti-cyclic citrullinated peptide antibody in CIA rats to 85.83% (p < 0.05) and notably alleviated synovial hyperplasia and cartilage degradation in joints. Different from methotrexate, MAN significantly augmented CD25(+) cells distribution (from 2.72 to 3.35%) and IL-10 secretion (from 202.4 to 241.2 pg/mL) in CIA rat blood. Meanwhile, MAN induced a greater IL-17 decrease and a FOXP3 increase in immune organs than MTX. Reduced TLR4 and IL-17 expression and elevated FOXP3 expression in joints also occurred under MAN treatment. Conclusions: MAN protected joints from destruction in CIA rats and exerted synergistic effects with methotrexate by improving immune microenvironment. The combination regimen could bring additional benefits to rheumatoid arthritis patients.