ANTIFIBROTIC POTENTIAL OF DRUGS AND POLYPHENOLS COMBINATIONS.

• Grant number: 22/11204-5
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: January 01, 2023
• End date: December 31, 2023
• Field of knowledge: Biological Sciences - Pharmacology - General Pharmacology
• Principal Investigator: Alessandra Gambero
• Grantee: Maria Carolina Ximenes de Godoy
• Host Institution: Escola de Ciências da Vida (ECV). Pontifícia Universidade Católica de Campinas (PUC-CAMP). Campinas , SP, Brazil

Abstract

The aging of the population is at an accelerated rate and there is an increase in diseases such as idiopathic pulmonary fibrosis, which is a disease that affects more the elderly population. Idiopathic pulmonary fibrosis is caused by the deposition of extracellular matrix in the interstitial space and the loss of epithelial cells from the alveoli. Since this disease manifests itself more frequently between the sixth and seventh decades of life, the role of senescent cells in pathophysiology has been discussed. Senescent cells produce a secretome that induces changes in neighboring cells and the extracellular matrix around them, leading to pulmonary fibrosis. The senescent fibroblasts of the lung are disease-associated cells. There are currently no effective treatment options for fibrosis. Two drugs are approved to treat pulmonary fibrosis: pirfenidone and nintedanib, which act by interfering with fibroblast proliferation and signaling pathways in the fibrosis process. If senescent cells may play a key role in the establishment of fibrosis, anti-senescence compounds have been studied. Senotherapeutics can be divided into senolytics and senostatics, with the first desatinib+quercetin being the most efficient in leading senescent cells to apoptosis (senolysis). Other drugs have demonstrated the ability to control the profibrotic secretome (senostatics), such as rapamycin and metformin. Some polyphenols such as mangiferin and resveratrol showed antifibrotic effects when used alone, and as the combination dasatinib+quercetin was a successful case for presenting synergistic actions, we hypothesized that polyphenols could have synergistic actions if added to the antifibrotics and senostatics. This study aims to evaluate the antifibrotic potential of senostatics or antifibrotic drugs in combination with polyphenols (chlorogenic acid, gallic acid, resveratrol, epicatechin and quercetin) for possible use in the management of pulmonary fibrosis using in vitro assays with senescent lung fibroblasts cells.