Genkwanin ameliorates adjuvant-induced arthritis in rats through inhibiting JAK/STAT and NF-κB signaling pathways

• Published in: Phytomedicine (Stuttgart) Vol. 63; p. 153036
• Main Authors: Bao, Yarigui, Sun, Yue-Wen, Ji, Jun, Gan, Lu, Zhang, Chun-Feng, Wang, Chong-Zhi, Yuan, Chun-Su
• Format: Journal Article
• Language: English
• Published: Germany Elsevier GmbH 01.10.2019
• Subjects: Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Arthritis, Experimental - drug therapy; Arthritis, Experimental - metabolism; Arthritis, Rheumatoid - drug therapy; Arthritis, Rheumatoid - metabolism; Cytokines - blood; Cytokines - metabolism; Flavones - pharmacology; Genkwanin; Inflammation; Inflammation - drug therapy; JAK/STAT; Janus Kinase Inhibitors - pharmacology; Male; NF-kappa B - metabolism; NF-κB; Phosphorylation - drug effects; Rats, Sprague-Dawley; Rheumatoid arthritis; Signal Transduction - drug effects; STAT Transcription Factors - antagonists & inhibitors; STAT Transcription Factors - metabolism; Synovial Membrane - drug effects; Synovial Membrane - metabolism; Synovial Membrane - pathology; IKK; Inflammation; JAK/STAT; RA; IκB; MTX; NF-κB; STAT; TG; JAK; Rheumatoid arthritis; AIA; Genkwanin; CFA
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2019.153036

Genkwanin is a flavone isolated from the traditional Chinese herb Daphne genkwa. Our previous work proved that four flavonoids (including genkwanin) isolated from D. genkwa (FFD) significantly improved the symptoms of arthritis in rat models. Recent studies have revealed that genkwanin exhibited anti-inflammatory and immunomodulatory activities, both of which were closely related to the pathology of rheumatoid arthritis (RA). Therefore, studying the anti-RA effects and mechanisms of genkwanin may give us insight into FFD's therapeutic effects on RA. This study aimed to investigate the anti-rheumatoid arthritis activity of genkwanin on adjuvant-induced arthritis (AIA) model in rats and explore the underlying mechanisms. The anti-rheumatoid arthritis activity of genkwanin was evaluated on AIA rat model by determining the paw swelling degrees and arthritis index scores, along with histopathological analysis of joint tissues. The serum cytokine levels were measured by ELISA method, and serum NO levels were measured by Griess method. The expression and phosphorylation levels of proteins in JAK/STAT and NF-κB signaling pathways were determined by western blot analysis and immunohistochemistry analysis. Genkwanin significantly decreased the paw swelling and arthritis index in AIA rats and also decreased the inflammation and bone destruction in joint tissues. The serum TNF-α, IL-6, and NO concentrations were markedly reduced while the IL-10 concentration was markedly increased with the treatment of genkwanin. Genkwanin inhibited the activation of JAK/STAT and NF-κB signaling pathways in synovial tissues of AIA rats. Genkwanin exerted anti-rheumatoid arthritis effects on AIA rats through inhibiting the activation of JAK/STAT and NF-κB signaling pathways. The results obtained in this work lead us to suggest that Genkwanin could play a crucial role on the previously demonstrated anti-rheumatoid arthritis activity of flavonoid extract of D. genkwa (namely FFD). [Display omitted]