Unraveling the mechanism involved in the mucosal healing promoted by Citral: role of tight junctions, cytokines, and growth factors

• Grant number: 24/01427-2
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate
• Start date: May 31, 2024
• End date: May 30, 2025
• Field of knowledge: Biological Sciences - Pharmacology - Ethnopharmacology
• Principal Investigator: Clélia Akiko Hiruma Lima
• Grantee: Felipe Leonardo Fagundes
• Supervisor: Eduardo Villablanca
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil
• Institution abroad: Karolinska Institutet, Sweden
• Associated to the scholarship: 22/02730-5 - Investigation of the pharmacological activity of Citral against TNBS-induced colitis with relapses in male and female rats, BP.DR

Abstract

Inflammatory bowel disease (IBD) is an emergingdisorder characterized by episodes ofremission and relapse that affects around 5 million of people worldwide. The two main forms ofthis disease are Crohn Disease (CD) and Ulcerative Colitis (UC). IBD has multifactorial etiology,but genetic predisposition, dysbiosis and immune cell activation are central events involved in theinitiation and progression of IBD. During IBD course there is a mucosal breakdown that results inepithelial cell death and disruption of tight junction, increasing the paracellular permeability andfavoring the entrance of microbes and luminal prod ucts. These events can be investigatedthrough intestinal organoids , an emerging platform that mimics the complex gut organization. Thepharmacological treatment of IBD is based in disease management using aminosalycilates ,corticoids and monoclonal antibodies, drugs that have several side effects , elevated costs and didnot promote a sustained mucosal healing. Given this, there is necessary search new drugscandidates that reduces inflammation and promotes healing. Citral is a monoterpene present insome vegetal species like Zingiber officinale and Cymbopogon citratus with provenantimicrobial , gastroprotective , and analgesic At the present, Citral treatment waseffective in the remission of colitis induced by trinitrobenzene sulfonic acid (TNBS) in male ratsbased in its anti inflammatory and antioxidant properties. In this sense, this project aims tocomprehend the Citral mechanism of action, addressing the influence in permeability andmucosal repair factors. The data obtained will elucidate the in vitro mechanism of Citral treatmentand generate knowledge about the effects of this monoterpene in IBD , allowing the inclusion ofthis monoterpene as effective and safe option in the colitis management.