title: Therapeutic potential of Oroxylin A in rheumatoid arthritis.
abstract: Excessive inflammation contributes greatly to the pathogenesis and development of rheumatoid arthritis (RA). Oroxylin A (OA) is a natural anti-inflammatory flavonoid compound. In this study, we investigated the effects of OA on collagen-induced arthritis (CIA) and human RA fibroblast-like synoviocytes (FLS). CIA was induced in DBA/1 mice and mice were intraperitoneally treated with OA (10mg/kg) for 10days. Arthritis severity was evaluated every day and the histopathologic examination of joints was done. Serum levels of anti-collagen II antibodies (anti-CII Abs) and cytokines were determined by ELISA. Frequency of regulatory T cells (Tregs) and Th17 cells in draining inguinal lymph nodes (ILN) was quantified by flow cytometry. FLS from patients with active RA were treated with varying doses of oroxylin A, followed by stimulation with tumor necrosis factor (TNF)-α (10ng/mL). The production of cytokines was measured by ELISA. Signal transduction proteins were examined by western blot. OA significantly diminished the arthritis and histological damage. Serum anti-CII Abs, IL-1β, IL-6, TNFα, and IL-17 were significantly diminished by OA treatment. Analysis of CD4+T cell populations in OA-treated mice showed an increase in Tregs and reduction in Th17 cells in the ILN. In vitro, OA decreased the secretion of IL-1β and IL-6 from TNFα-stimulated RA FLS in a dose-dependent manner. TNFα-induced p38 MAPK, ERK1/2 and NF-κB signaling pathways were suppressed by OA. Our results indicate that OA exerts an anti-inflammatory activity and may have therapeutic potential for human RA.
authors.affiliation: Department of Rheumatology and Immunology, Linyi People's Hospital, Linyi 276003, Shandong, China.
authors.forename: Yu-Ling
authors.initials: YL
authors.lastname: Wang
authors.affiliation: Department of Rheumatology and Immunology, Yishui Central Hospital, Linyi 276400, Shandong, China.
authors.forename: Ju-Mei
authors.initials: JM
authors.lastname: Gao
authors.affiliation: Department of Endocrinology, Linyi People's Hospital, Linyi 276003, Shandong, China. Electronic address: xing_lizhi@yeah.net.
authors.forename: Li-Zhi
authors.initials: LZ
authors.lastname: Xing
mesh_terms: D000818:Animals; D000843:Ankle Joint / Q000187:drug effects / Q000473:pathology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D001172:Arthritis, Rheumatoid / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology; D005419:Flavonoids / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D008811:Mice, Inbred DBA; D000070918:Synoviocytes / Q000187:drug effects / Q000276:immunology; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D058504:Th17 Cells / Q000276:immunology
chemical_list: D000893:Anti-Inflammatory Agents; D016207:Cytokines; D005419:Flavonoids; C080669:5,7-dihydroxy-6-methoxy-2-phenylchromen-4-one
keywords: Collagen-induced arthritis; Fibroblast-like synoviocytes; Oroxylin A; Rheumatoid arthritis