Investigation of the pharmacological activity of Citral against TNBS-induced colitis with relapses in male and female rats

• Grant number: 22/02730-5
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: November 01, 2022
• End date: June 01, 2026
• Field of knowledge: Biological Sciences - Pharmacology - Ethnopharmacology
• Principal Investigator: Clélia Akiko Hiruma Lima
• Grantee: Felipe Leonardo Fagundes
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Associated scholarship(s): 24/01427-2 - Unraveling the mechanism involved in the mucosal healing promoted by Citral: role of tight junctions, cytokines, and growth factors, BE.EP.DR

Abstract

Inflammatory bowel disease (IBD), which includes Crohn's disease (CD) and ulcerative colitis (UC) is a chronic and recurrent disease of the gut, characterized by lifelong illness in men and women. Patients abandon treatment due to side effects caused by the available drugs. In this sense, new biomolecules with potential for the treatment of IBDs are sought in natural products. Citral is a monoterpene present on essential oils of medicinal plants, such as Cymbopogon citratus, which has anti-inflammatory and antioxidant action in peptic ulcer models. In addition to antimicrobial, antipyretic, and antihyperlipidemic actions, without their effects having been investigated in colitis. Thus, this project seeks to evaluate the healing potential of Citral in the colitis induced by 2,4,6 trinitrobenzene sulfonic acid (TNBS) in Wistar rats (male and female), as well as to characterize the mechanisms of antioxidant action (superoxide dismutase, catalase, and glutathione reduced), inflammatory (myeloperoxidase and eosinophilic peroxidase activity), production of pro-inflammatory and anti-inflammatory cytokines (IL-1b, IL-6, TNF-a e IL-10), gene expression of factors involved in the immune system activation and intestinal repair (MCP-1, TLR4, TFF3, MUC2 e MUC3) and protein expression from intestinal tight junctions (ZO-1, CLND-4, OCLN) and analysis of fecal microbiome. The results obtained with this proposal will provide information about the Citral mechanism considering the sexes, in addition to providing information for future incorporation of monoterpene in the treatment of IBD.