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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. 41:2184-2195
- Publication Year :
- 2018
- Publisher :
- Springer Science and Business Media LLC, 2018.
-
Abstract
- 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.
- Subjects :
- 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
Subjects
Details
- ISSN :
- 15732576 and 03603997
- Volume :
- 41
- Database :
- OpenAIRE
- Journal :
- Inflammation
- Accession number :
- edsair.doi.dedup.....536b96880d12b8c36e248a68364c51b6