Inhibitory effects of punicalagin from Punica granatum against type II collagenase-induced osteoarthritis

Pomegranate (Punica granatum) is a heath with abundant hydrolysable tannin in its peel. This study demonstrated that POMx (70% acetone extract of pomegranate peels) significantly reduced interleukin (IL)-1β-induced inducible nitric oxide synthase, cyclooxygenase-2, and matrix metalloproteinase-13 protein expression in primary rat chondrocytes (PRCs). In the type II collagenase-induced osteoarthritis rat model, POMx (150 mg/kg) recovered the weight-bearing ratio changes in experimental animals, suggesting the alleviation of knee-related inflammation and nociception. Therefore, the major compound, punicalagin, was isolated from POMx. Punicalagin also significantly reduced IL-1β-induced inflammatory factors in PRCs and exerted significant antiosteoarthritis effects in the vivo model after 28-d treatment (concentration: 0.50 mg/kg). However, the IC₅₀ values of POMx and punicalagin against prostaglandin E₂ production were 83.2 and 36.0 μg/mL, respectively, and the concentration of punicalagin in POMx was 19.1%. Altogether, POMx can be used to develop functional foods for knee-related diseases, and punicalagin can act as an active ingredient.