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.