Topical Anti-Inflammatory and Analgesic Activities of Extract Cream in Rats.

(CC), known as bitter apple, is used to treat diabetes in Iranian traditional medicine. The aim of this study is to evaluate the anti-inflammatory and analgesic activities of CC cream in rats. The carrageenan-induced edema in a rat hind paw was carried out to evaluate the topical anti-inflammatory effect of the CC fruit extract cream (2⁻8%) and the tissue levels of IL-6 and TNF-α were estimated by using a commercial ELISA kit. The topical antinociceptive activity of CC cream (2⁻8%) was evaluated in the rat formalin test. To determine the role of opioid receptors in the local antinociceptive effect of the CC cream, naloxone (20 μg/paw, i.pl.), a non-selective opioid antagonist, was used. The results showed that the CC cream (2⁻8%) dose-dependently reduced the carrageenan-induced paw edema and reversed the changes in the level of TNF-α and IL-6 due to carrageenan-induced edema ( < 0.01). The anti-inflammatory effect of CC cream 8% was comparable to that of hydrocortisone ointment 1%. Furthermore, the application of CC cream (2⁻8%) dose-dependently inhibited both first and second phases of the formalin test ( < 0.05). The antinociceptive effect of the CC cream (8%) was comparable to that of methyl salicylate cream 30%. Moreover, the administration of naloxone significantly reversed the topical antinociceptive effect of the CC cream ( < 0.05). For the first time, this study indicated that the topical application of CC cream possesses significant anti-inflammatory and antinociceptive activities in animal models, which were probably mediated by opioid receptors and the suppression of pro-inflammatory cytokines (TNF-α and IL-6). Thus, the CC cream can be used to treat inflammatory pain and inflammatory diseases.