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EFFECTS OF PAEONIFLORIN EXTRACT-MEDIATED miRNA-140 TARGETING OF WNT/β-CATENIN SIGNALLING PATHWAY ON PROLIFERATION AND APOPTOSIS OF CHONDROCYTES IN OSTEOARTHRITIS

CHANGSHEN BAO, JIAN LUO, YONGJUN MENG, ZHICHAO GAO *

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The aim of this study was to evaluate the effects of paeoniflorin extract (Pae) on chondrocyte proliferation and apoptosis in osteoarthritis, with emphasis on miR-140 regulation and modulation of the Wnt/β-catenin signalling pathway. The work comprised two components. First, paeoniflorin extract was characterised, and its pharmacokinetics were assessed following oral administration and intestinal perfusion. Second, its anti-inflammatory efficacy was examined in an IL-1β-stimulated human chondrocyte model (C28/I2). In vitro within-day precision ranged from 2.16% to 4.27%, inter-day precision from 1.85% to 5.08%, recovery was 72.88% - 77.41%, and relative standard deviation values were all < 15%. After gavage, effective intestinal permeability coefficients were 0.26 - 0.34, with peak plasma concentrations at 3 - 4 hours; absorption and elimination half-lives ranged from 0.667 - 1.124 h and 1.250 - 1.881 h, respectively. In vitro, IL-1β reduced cell proliferation, increased apoptosis, downregulated miR-140, DVL2, Cyclin D1 and β-catenin, and upregulated GSK-3β (p < 0.05). Treatment with low, medium and high concentrations of Pae reversed these effects in a dose-dependent manner (p < 0.05). Overall, paeoniflorin extract upregulated miR-140 and modulated Wnt/β-catenin signalling, thereby attenuating IL-1β-induced chondrocyte dysfunction.