Avaliação do Efeito Anti-inflamatório do Diterpeno Annonalida Oriundo da Casimirella Ampla (miers) em Modelos Experimentais de Inflamação Geral

Abstract

Inflammation is a fundamental response of primary protection of the organism against injury or invasion of pathogens. The inflammatory response is initiated by a multitude of endogenous and exogenous stimuli with characteristic symptoms. The compounds isolated from plants with anti-inflammatory activity have been alternative therapeutic sources, which replace many drugs with unsatisfactory side effects. An interesting source of natural products to treat various pathological conditions are medicinal plants, among them is Casimirella ampla (C. ampla) which has few studies investigating its therapeutic effects, but in its roots they have diterpenoid compounds that are investigated for their involvement. during the inflammatory response, thus being a

promising source of molecules. The present study aims to evaluate the possible anti- inflammatory effect of diterpene annonalide (An) extracted from C. ampla in mouse

models of general inflammation. The anti-inflammatory activity of compound An was investigated using animal models, in which their use was approved by the Committee on Ethics in Animal Use (CEUA) of the Federal University of Piauí – UFPI under number 020/19. The experimental protocols followed the norms and guidelines of the Brazilian College of Animal Experimentation (COBEA). Swiss mice weighing between 25-30g were used, with 6 animals per group. For the anti-inflammatory evaluation, the animals were pre-treated with An at doses of 0.1; 1.0 or 10 mg/kg orally (v.o.) and subsequently submitted to a paw edema induced by carrageenan (Cg) 500 μg per paw in order to evaluate a possible anti-inflammatory participation of this compound and to perform the screening with the purpose of choose a better dose with anti-inflammatory effect that would be used in the other tests. A group that received a physiological saline solution 0.9% and a group with the reference drug indomethacin (Indo) 10 mg/kg were also used. After Cg edema, the segments of the supplant region of the animals' paws were removed and used for histopathological and myeloperoxidase (MPO) enzyme evaluation. The animals also underwent paw edema by the vasoactive mediators histamine (100 μg/paw) and serotonin (100 μg/paw), peritonitis was also induced with an injection of 250 μg of Cg intraperitoneal (i.p.) in the mice and the peritoneal fluid was evaluated for leukocyte migration and glutathione (GSH) levels. The animals treated with An 0.1 mg/kg showed relevant and statistically significant results in the reduction of edema caused by Cg, as well as in the vascular response due to the reduction of vascular edema caused by histamine and serotonin. Furthermore, said compound was effective in reducing microscopic lesions of the paw tissue, MPO enzyme levels and cell migration to the peritoneal cavity, as well as increasing GSH levels. The results obtained allow us to infer that the compound derived from C. ampla An at a dose of 0.1 mg/kg has an anti-inflammatory effect and attenuates oxidative

stress, revealing a pharmacological potential of the compound as a promising anti- inflammatory agent.