Epiisopiloturina atenua os efeitos pró inflamatórios da colite experimental através do receptor M1.

Abstract

Ulcerative colitis is a chronic disease that affects the colon and rectum, characterized by ulcerations of the mucosa and submucosa of the colon without affecting the deeper layers of the intestinal wall. Currently, the conventional therapies used to treat ulcerative colitis aim to control inflammation, relieve abdominal pain and maintain remission of the disease. However, these therapies are associated with a variety of side effects that hinder their use. An alternative is the use of natural compounds with promising properties for the treatment of this pathology. One of the main alkaloids extracted from jaborandi is epiisopiloturine, which has a chemical structure similar to pilocarpine, and has been shown to be a promising alkaloid in terms of its anti-inflammatory effects demonstrated in previous studies, it is important to study which way this effect happens. Objective: This study aims to evaluate the participation of the muscarinic M1 receptor in the anti-inflammatory response of epiisopiloturine 17 hours after induction of acetic acid-induced colitis. Methods: A molecular docking study of epiisopiloturine with the M1 muscarinic receptor was initially carried out. The anti-inflammatory activity of Epiisopiloturine in the course of colitis induced by acetic acid was evaluated by administering the substance in doses of 0.01; 0.1 and 1.0 mg / kg intraperitoneally. To analyze the participation of the cholinergic system, but specifically of the muscarinic M1 receptor in the mechanism of anti-inflammatory action of epiisopiloturine in acetic acid colitis, its action was blocked using pirenzepine (M1 receptor antagonist). The macroscopic and microscopic scores, the biochemical parameters of the lesion (MPO, MDA, GSH, NO2/NO3) were evaluated, as well as the measurement of cytokines and immunoexpression by western blot. Results and discussion: In the initial study of molecular docking, epiisopiloturine demonstrated a link affinity with the muscarinic receptor M1. Epiisopiloturine at a dose of 0.1 mg / kg showed a better anti-inflammatory effect by decreasing inflammatory parameters, in the course of colitis induced by acetic acid. The groups of animals treated simultaneously with epiisopiloturine at a dose of 0.1 mg / kg and co-treated with the cholinergic antagonist pirenzepine, showed a reduction in the anti-inflammatory effects of epiisopiloturine, thus demonstrating the blocking of its action by pirenzepine. Conclusion: Based on the results obtained, the present study infers that epiisopiloturine has its anti-inflammatory action through the M1 muscarinic receptor, since blocking the receptor with the pharmacological antagonist reduced the anti- inflammatory effects of the drug in the course of experimental colitis, pointing out that the molecule is a promising alternative for the treatment of ulcerative colitis.