Therapeutic Effect of Penta-acetyl Geniposide on Adjuvant-Induced Arthritis in Rats: Involvement of Inducing Synovial Apoptosis and Inhibiting NF-κB Signal Pathway
Autor: | Ming-ming Liu, Chun-mei Li, Rong Li, Wen-jian Tang, Li Cai, Yuan-ye Qiu, Wei-na Chen |
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Rok vydání: | 2018 |
Předmět: |
0301 basic medicine
Iridoid Glucosides Immunology Arthritis Apoptosis Caspase 3 Pharmacology 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine NF-KappaB Inhibitor alpha Western blot In vivo medicine Animals Immunology and Allergy Phosphorylation 030203 arthritis & rheumatology TUNEL assay medicine.diagnostic_test Chemistry Synovial Membrane NF-kappa B Transcription Factor RelA NF-κB medicine.disease Arthritis Experimental Rats IκBα 030104 developmental biology Signal Transduction |
Zdroj: | Inflammation. 41:2184-2195 |
ISSN: | 1573-2576 0360-3997 |
Popis: | Previous studies demonstrated that penta-acetyl geniposide ((Ac)5GP, an acetylated derivative of geniposide) exhibited better pharmacological functions than geniposide. This study was aimed to observe the potential effect of (Ac)5GP on adjuvant-induced arthritis (AIA) in rat and explore the involved mechanisms. Rat AIA was induced by complete Freund’s adjuvant. (Ac)5GP (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)5GP on rat AIA. Immunohistochemistry for Ki67 and TUNEL assay were performed to reveal the anti-proliferative and pro-apoptotic effects of (Ac)5GP 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)5GP 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)5GP treatment also could reduce Ki67 positive expression rate and raise the synovial apoptosis index in synovial tissues. Additionally, (Ac)5GP (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)5GP (120 mg/kg) could inhibit the degradation and phosphorylation of IκBα and reduce NF-κB p65 protein level in nuclear extracts. In conclusion, (Ac)5GP showed a potent anti-arthritic effect on AIA rats via inducing synovial apoptosis and inhibiting NF-κB activation in synovial tissues. |
Databáze: | OpenAIRE |
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