Efeito do alcalóide indólico Caulerpina nos modelos murinos de peritonite e edema de orelha

Abstract

The appearance of adverse effects associated with the use of corticosteroids has driven the search for compounds derived from natural products with pharmacological properties, so that they can be used as an alternative anti-inflammatory therapy. Thus, the present study sought to assess the anti-inflammatory potential of caulerpin (CLP), an alkaloid derived from algae of the genus Caulerpa, in murine models of zimosaninduced peritonitis and xylene-induced ear edema. For this, mice were orally treated with CLP at doses of 4, 2, 1 mg/kg and dexamethasone (1 mg/kg) and 1 hour later received zymosan (40 mg/kg) intraperitoneally. After 24 hours, the peritoneal lavage was collected and the number of cells was determined. The same procedure was repeated to assess the migration kinetics and presence of cytokines in the peritoneal lavage at 6, 24 and 48 hours. For ear edema, the animals were treated with the same different doses of CLP, followed by topical application of xylene (40μL) in the right ears, 1 hour after treatment. The level of edema was determined by calculating the percentage of inhibition and morphological analysis evaluated in equal sections of the removed ears. In the peritonitis model, pre-treatment with CLP was able to reduce cell migration to the peritoneal cavity at doses of 4, 2 and 1 mg/kg, with the dose of 2 mg/kg being the one that showed results more expressive in inhibiting cell migration. In the cell migration kinetics, using the dose of 2 mg/kg of CLP, it was observed that this dose was able to inhibit this event in the three evaluated times, after the administration of zymosan. And this effect was related to the decrease in the levels of IL-1β and IL-6 in the peritoneal lavage, during the studied kinetics. In the edema model, it was observed that the three CLP doses tested acted by inhibiting the formation of xylene-induced ear edema, which was demonstrated by the high percentages of inhibition of the process (based on the weight of the ear sections) and in the preservation of the tissue morphology of the ears in the animals that received the treatments, with the dose of 2 mg/kg being the most efficient in this inhibition. Thus, the CLP has anti-inflammatory activity in the models studied and the dose of 2 mg/kg is an optimal dose in controlling inflammation in the models of peritonitis induced by zimosan and xylol-induced ear edema.