title: Potent Antiarthritic Properties of Phloretin in Murine Collagen-Induced Arthritis.
abstract: In the exploration of potential therapeutic agents for rheumatoid arthritis (RA), DBA/1J mice are used as the RA model of collagen-induced arthritis (CIA). Phloretin, a flavonoid compound extracted fromPrunus mandshurica, has been found to exhibit anti-inflammatory activity, making it a potential candidate for treatment of RA. The objective of this study was to evaluate the therapeutic effects of phloretin on CIA mice. CIA mice were dosed daily with phloretin at either 50 or 100 mg/kg among two treatment groups. CIA treated mice showed mitigation of clinical symptoms of RA in addition to reduced inflammation of hind-limbs compared to mice who did not receive phloretin. Histological analysis showed that phloretin suppressed the severity of RA and effectively mitigated joint inflammation and cartilage- and bone-destruction via reducing proinflammatory cytokine productions (TNF-α, IL-6, IL-1β, and IL-17). This was at least partially mediated by causing inadequate splenocyte activation and proliferation. Moreover, phloretin-treated CIA mice showed decreased oxidative stress and diminished levels of malondialdehyde (MDA) and hydrogen peroxide (H2O2) in paw tissues as well as reduced productivity of anti-collagen antibodies in serum. We have concluded that phloretin could be a potent and effective antiarthritis agent, demonstrating anti-inflammatory, antioxidative, and immunomodulatory effects in CIA mice.
authors.affiliation: Department of Life Science, Tunghai University, Taichung, Taiwan; Department of Orthopaedics, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Shun-Ping
authors.initials: SP
authors.lastname: Wang
authors.affiliation: Ph.D. Program in Medical Biotechnology, National Chung Hsing University, Taichung, Taiwan; SRI International, Harrisonburg, VA, USA.
authors.forename: Shih-Chao
authors.identifier: 0000-0003-2942-5937
authors.initials: SC
authors.lastname: Lin
authors.affiliation: Hubei Key Laboratory of Economic Forest Germplasm Improvement and Resources Comprehensive Utilization and Hubei Collaborative Innovation Center for the Characteristic Resources Exploitation of Dabie Mountains, Huanggang Normal University, Huanggang, Hubei, China.
authors.forename: Shiming
authors.initials: S
authors.lastname: Li
authors.affiliation: Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Ya-Hsuan
authors.initials: YH
authors.lastname: Chao
authors.affiliation: Department of Life Science, Tunghai University, Taichung, Taiwan.
authors.forename: Guang-Yuh
authors.identifier: 0000-0002-8477-7487
authors.initials: GY
authors.lastname: Hwang
authors.affiliation: Institute of Biomedical Science, National Chung Hsing University, Taichung, Taiwan; Department of Biotechnology, Asia University, Taichung, Taiwan; Department of Medical Research, China Medical University Hospital, Taichung, Taiwan.
authors.forename: Chi-Chen
authors.identifier: 0000-0002-1464-0231
authors.initials: CC
authors.lastname: Lin