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

Medicina (Kaunas). 2018 Jul 29;54(4):51. doi: 10.3390/medicina54040051.


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,, 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 < 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 < 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 < 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.

Keywords: Citrullus colocynthis; anti-inflammatory; antinociceptive; cream; rat.

MeSH terms

  • Administration, Topical
  • Analgesics / administration & dosage
  • Analgesics / therapeutic use*
  • Animals
  • Anti-Inflammatory Agents / administration & dosage
  • Anti-Inflammatory Agents / therapeutic use*
  • Citrullus colocynthis*
  • Disease Models, Animal
  • Edema / drug therapy*
  • Enzyme-Linked Immunosorbent Assay
  • Male
  • Plant Extracts / administration & dosage
  • Plant Extracts / therapeutic use*
  • Rats
  • Rats, Sprague-Dawley
  • Skin Cream / administration & dosage
  • Skin Cream / therapeutic use*


  • Analgesics
  • Anti-Inflammatory Agents
  • Plant Extracts