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Background and objectives:  Citrullus colocynthis (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. Materials and Methods: 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. Results: 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 ( p &lt; 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 ( p &lt; 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 ( p &lt; 0.05). Conclusions: 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.

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