Evaluation of the synergistic effect of 4-methylesculetin and piperine on DSS-induced intestinal inflammation in mice

• Grant number: 23/15202-0
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: March 01, 2024
• End date: December 31, 2024
• Field of knowledge: Biological Sciences - Pharmacology - Ethnopharmacology
• Principal Investigator: Luiz Claudio Di Stasi
• Grantee: Juliana Saraiva Zanelato Andrade
• Host Institution: Instituto de Biociências (IBB). Universidade Estadual Paulista (UNESP). Campus de Botucatu. Botucatu , SP, Brazil

Abstract

Inflammatory Bowel Disease (IBD) is a chronic non-communicable disease, categorized in Crohn's Disease (CD) and Ulcerative Colitis (UC), depending on the patient's inflammation. IBD etiology is not clear, but it involves genetic factors, lifestyle, environmental factors, dysregulation of the immune response, among others. However, previous studies indicate that intestinal inflammation is directly related to increased oxidative stress, resulting from excessive amounts of reactive oxygen species (ROS) and reactive nitrogen species (RNS), which induce the degradation of proteins and cell membranes, displaying spread and advancement of the disease. 4-methylesculetin (4-ME), a coumarin derivative with antioxidant and intestinal anti-inflammatory activity, acting through different antioxidant mechanisms, especially sequestering reactive oxygen species, modulating oxidative stress through reducing glutathione depletion and reducing myeloperoxidase. Piperine (PP) is a piperine alkaloid that acts as an intestinal anti-inflammatory agent, activating pregnane X receptor and modulating NF- ºB and Toll-like receptor (TLR4). Piperine is widely used as a product that facilitates the absorption processes and availability of other chemical compounds. The intestinal anti-inflammatory effects of 4-methylesculetin and piperine previously described in different experimental models indicate that these compounds act through different mechanisms, indicating the possibility that, when administered in combination, their effects can be enhanced via synergistic action, generating a product with potential applications in preventing and controlling the progression of IBD.