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Therapeutic Effect of Penta-acetyl Geniposide on Adjuvant-Induced Arthritis in Rats: Involvement of Inducing Synovial Apoptosis and Inhibiting NF-κB Signal Pathway.
- Source :
-
Inflammation [Inflammation] 2018 Dec; Vol. 41 (6), pp. 2184-2195. - Publication Year :
- 2018
-
Abstract
- Previous studies demonstrated that penta-acetyl geniposide ((Ac) <subscript>5</subscript> GP, an acetylated derivative of geniposide) exhibited better pharmacological functions than geniposide. This study was aimed to observe the potential effect of (Ac) <subscript>5</subscript> GP on adjuvant-induced arthritis (AIA) in rat and explore the involved mechanisms. Rat AIA was induced by complete Freund's adjuvant. (Ac) <subscript>5</subscript> 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) <subscript>5</subscript> GP on rat AIA. Immunohistochemistry for Ki67 and TUNEL assay were performed to reveal the anti-proliferative and pro-apoptotic effects of (Ac) <subscript>5</subscript> 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) <subscript>5</subscript> 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) <subscript>5</subscript> GP treatment also could reduce Ki67 positive expression rate and raise the synovial apoptosis index in synovial tissues. Additionally, (Ac) <subscript>5</subscript> 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) <subscript>5</subscript> 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) <subscript>5</subscript> GP showed a potent anti-arthritic effect on AIA rats via inducing synovial apoptosis and inhibiting NF-κB activation in synovial tissues.
- Subjects :
- Animals
Iridoid Glucosides pharmacology
NF-KappaB Inhibitor alpha metabolism
Phosphorylation drug effects
Rats
Signal Transduction drug effects
Synovial Membrane chemistry
Transcription Factor RelA drug effects
Transcription Factor RelA metabolism
Apoptosis drug effects
Arthritis, Experimental drug therapy
Iridoid Glucosides therapeutic use
NF-kappa B antagonists & inhibitors
Synovial Membrane pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1573-2576
- Volume :
- 41
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Inflammation
- Publication Type :
- Academic Journal
- Accession number :
- 30069664
- Full Text :
- https://doi.org/10.1007/s10753-018-0861-0