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Alpha-mangostin: Anti-inflammatory and antioxidant effects on established collagen-induced arthritis in DBA/1J mice

Diana Rocio Herrera-Aco¹, Omar Noel Medina-Campos², José Pedraza-Chaverri²

¹Facultad de Medicina Veterinaria y Zootecnia, Universidad Nacional Autónoma de México, Ciudad Universitaria s/n, Ciudad de México, 04650, Mexico.

Food and Chemical Toxicology : an International Journal Published for the British Industrial Biological Research Association

|December 18, 2018

Abstract:

Rheumatoid arthritis (RA) is an autoimmune disease that causes physical disability in people worldwide. Despite progress made in RA treatment in the past decade, new drugs with high efficacy but few long-term adverse effects are still needed. This study focused on evaluating the therapeutic potential of α-mangostin on established collagen-induced arthritis (CIA) in DBA/1J mice. Arthritic DBA/1J mice were orally administered with two doses of α-mangostin (10 and 40 mg/kg) daily, for 33 days. Alpha-mangostin significantly decreased the clinical score in the short term at both doses and decreased the histopathological score at the higher dose. This improvement was accompanied by a reduction on serum levels of anti-collagen IgG2a autoantibodies and of the production of LIX/CXCL5, IP-10/CXCL10, MIG/CXCL9, RANTES/CCL5, IL-6 and IL-33 in the joints of CIA mice. Alpha-mangostin also exhibited an anti-oxidant effect decreasing the NADPH oxidase activity and lipid peroxidation and preserving the levels of reduced glutathione in the arthritic joints. In vitro this xanthone demonstrated modulatory properties on LPS-activated dendritic cells, although in Th1 and Th17-polarized lymphocytes promotes a pro-apoptotic phenotype. Altogether this study illustrates the capacity of α-mangostin to ameliorate the early clinical and histological signs of established CIA by reducing the inflammatory and oxidative responses.

Insights

Alpha-mangostin shows promise in treating rheumatoid arthritis (RA). This study found it reduced inflammation and oxidative stress in mice with collagen-induced arthritis (CIA), suggesting a potential new therapeutic approach.

Area of Science:

Immunology
Pharmacology
Rheumatology

Background:

Rheumatoid arthritis (RA) is a disabling autoimmune disease with ongoing needs for effective treatments.
Current RA therapies require improvement regarding efficacy and long-term adverse effects.

Purpose of the Study:

To evaluate the therapeutic potential of alpha-mangostin in a collagen-induced arthritis (CIA) mouse model.
To investigate the anti-inflammatory and anti-oxidant effects of alpha-mangostin in established CIA.

Main Methods:

Established collagen-induced arthritis (CIA) in DBA/1J mice.
Administered oral doses of alpha-mangostin (10 and 40 mg/kg) daily for 33 days.
Assessed clinical and histopathological scores, autoantibody levels, cytokine production, and oxidative stress markers.

Main Results:

Alpha-mangostin significantly reduced clinical scores at both doses and histopathological scores at the higher dose.
Reduced serum levels of anti-collagen IgG2a autoantibodies and joint production of inflammatory mediators (LIX/CXCL5, IP-10/CXCL10, MIG/CXCL9, RANTES/CCL5, IL-6, IL-33).
Demonstrated anti-oxidant effects by decreasing NADPH oxidase activity, lipid peroxidation, and preserving glutathione levels in arthritic joints.

Conclusions:

Alpha-mangostin ameliorates early clinical and histological signs of established CIA in mice.
The therapeutic effects are linked to the reduction of inflammatory and oxidative responses.
Alpha-mangostin exhibits potential as a novel therapeutic agent for rheumatoid arthritis.

Read full analysis

Keywords:

Collagen-induced arthritis Inflammation Oxidative stress Rheumatoid arthritis α-mangostin

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