title: Combination therapy with metformin and coenzyme Q10 in murine experimental autoimmune arthritis.
abstract: Metformin (Met) and coenzyme Q10 (CoQ10) are reported to have therapeutic functions in several inflammatory diseases. These drugs have shown anti-inflammatory effects and have been utilized in mouse models of rheumatoid arthritis (RA). However, there is no evidence of the additive effect of Met and CoQ10 in RA. Although Met and CoQ10 may be involved in the improvement of mitochondrial dysfunction, limited information is available regarding whether this effect can improve mitochondrial dysfunction in RA in particular. In this study, we sought to determine whether Met and CoQ10 attenuate the severity of collagen-induced arthritis (CIA) and show an additive effect in a mouse model. The combination of Met and CoQ10 improved CIA, reducing joint inflammation, Th17 differentiation and IgG production. In contrast, the combination of Met and CoQ10 induced Treg differentiation. Osteoclastogenesis was reduced by the combination of Met and CoQ10. The protein expression of interleukin-1β, interleukin-6 and tumor necrosis factor-alpha in mice splenocytes exposed to lipopolysaccharide decreased after drug combination therapy. We also found that the expression of JC-1 and COX IV were enhanced by treatment with the combination of Met and CoQ10. Moreover, the combination of Met and CoQ10 promoted mitochondrial O2 consumption. These findings suggest that the combination of Met and CoQ10 reduced CIA severity, improving mitochondrial dysfunction compared to Met or CoQ10 alone. These results present a novel, significant preventive targets in RA and may enhance our understanding of its pathogenesis.
authors.affiliation: a The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea , Seoul , South Korea .|b Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea , Seoul , South Korea .
authors.forename: JooYeon
authors.initials: J
authors.lastname: Jhun
authors.affiliation: a The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea , Seoul , South Korea .|b Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea , Seoul , South Korea .
authors.forename: SeungHoon
authors.initials: S
authors.lastname: Lee
authors.affiliation: a The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea , Seoul , South Korea .|b Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea , Seoul , South Korea .
authors.forename: Se-Young
authors.initials: SY
authors.lastname: Kim
authors.affiliation: a The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea , Seoul , South Korea .|b Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea , Seoul , South Korea .
authors.forename: Hyun Sik
authors.initials: HS
authors.lastname: Na
authors.affiliation: a The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea , Seoul , South Korea .|b Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea , Seoul , South Korea .
authors.forename: Eun-Kyung
authors.initials: EK
authors.lastname: Kim
authors.affiliation: a The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea , Seoul , South Korea .|b Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea , Seoul , South Korea .
authors.forename: Jae-Kyung
authors.initials: JK
authors.lastname: Kim
authors.affiliation: d Impact Biotech , Seoul , South Korea.
authors.forename: Jeong-Hee
authors.initials: JH
authors.lastname: Jeong
authors.affiliation: a The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea , Seoul , South Korea .|c Divison of Rheumatology, Department of Internal Medicine, The Catholic University of Korea , Seoul , South Korea , and.
authors.forename: Sung Hwan
authors.initials: SH
authors.lastname: Park
authors.affiliation: a The Rheumatism Research Center, Catholic Research Institute of Medical Science, The Catholic University of Korea , Seoul , South Korea .|b Conversant Research Consortium in Immunologic Disease, College of Medicine, The Catholic University of Korea , Seoul , South Korea .
authors.forename: Mi-La
authors.initials: ML
authors.lastname: Cho
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology / Q000473:pathology; D002454:Cell Differentiation / Q000187:drug effects* / Q000276:immunology; D016207:Cytokines / Q000276:immunology; D004359:Drug Therapy, Combination; D005786:Gene Expression Regulation / Q000187:drug effects / Q000276:immunology; D007074:Immunoglobulin G / Q000276:immunology; D008297:Male; D008687:Metformin / Q000494:pharmacology*; D051379:Mice; D050378:T-Lymphocytes, Regulatory / Q000276:immunology* / Q000473:pathology; D058504:Th17 Cells / Q000276:immunology* / Q000473:pathology; D014451:Ubiquinone / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D016207:Cytokines; D007074:Immunoglobulin G; D014451:Ubiquinone; D008687:Metformin; C024989:coenzyme Q10
keywords: Coenzyme Q10; inflammatory; metformin; mitochondria; rheumatoid arthritis