Therapeutic Effect of Penta-acetyl Geniposide on Adjuvant-Induced Arthritis in Rats: Involvement of Inducing Synovial Apoptosis and Inhibiting NF-κB Signal Pathway
Inflammation(2018)
Abstract
Previous studies demonstrated that penta-acetyl geniposide ((Ac) 5 GP, an acetylated derivative of geniposide) exhibited better pharmacological functions than geniposide. This study was aimed to observe the potential effect of (Ac) 5 GP on adjuvant-induced arthritis (AIA) in rat and explore the involved mechanisms. Rat AIA was induced by complete Freund’s adjuvant. (Ac) 5 GP (30, 60, 120 mg/kg) was given to AIA rats by intragastric administration. Paw swelling, polyarthritis index, serum pro-inflammatory cytokines levels, histological assessments of ankle joint, and proteoglycan expression were respectively measured to evaluate the therapeutic effect of (Ac) 5 GP on rat AIA. Immunohistochemistry for Ki67 and TUNEL assay were performed to reveal the anti-proliferative and pro-apoptotic effects of (Ac) 5 GP on AIA synoviocytes in vivo . Protein levels of Bcl-2, Bax, caspase 3, IκBα, p-IκBα, and NF-κB p65 in synovial tissues were detected by Western blot. We found that (Ac) 5 GP treatment could suppress secondary hind paw swelling, reduce polyarthritis index, decrease TNF-α and IL-1β serum levels, attenuate pathological damage of ankle joint, and promote proteoglycans expression. (Ac) 5 GP treatment also could reduce Ki67 positive expression rate and raise the synovial apoptosis index in synovial tissues. Additionally, (Ac) 5 GP (120 mg/kg) could significantly decrease Bcl-2 protein level, increase Bax and cleaved caspase 3 protein levels, and normalize the ratio of Bcl-2 to Bax. Moreover, (Ac) 5 GP (120 mg/kg) could inhibit the degradation and phosphorylation of IκBα and reduce NF-κB p65 protein level in nuclear extracts. In conclusion, (Ac) 5 GP showed a potent anti-arthritic effect on AIA rats via inducing synovial apoptosis and inhibiting NF-κB activation in synovial tissues.
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Key words
adjuvant-induced arthritis,inflammation,NF-κB signal pathway,penta-acetyl geniposide,synovial apoptosis
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