New formulations of green propolis extracts: comparative studies of bioaccessibility, intestinal permeability and biotransformation of their bioactive constituents.

• Grant number: 24/05555-5
• Support Opportunities: Regular Research Grants
• Start date: April 01, 2025
• End date: March 31, 2027
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Niege Araçari Jacometti Cardoso Furtado
• Grantee: Niege Araçari Jacometti Cardoso Furtado
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated researchers: Andresa Aparecida Berretta e Silva

Abstract

The studies proposed in this project on bioaccessibility, intestinal permeability and biotransformation of the bioactive constituents of new formulations of green propolis extracts are unprecedented and are expected to add value to these products of Brazilian biodiversity, bringing to light knowledge that will enable the filling of gaps aimed at developing of standardized medicines of natural origin with quality, safety and efficacy. One of the major bottlenecks in research in Brazil is the lack of studies on the absorption, distribution, metabolism and excretion of natural bioactive compounds. Considering that the export of raw green propolis is one of the pillars of the Brazilian beekeeping economy, the development of products with greater added value, based on our biodiversity, constitutes an immense possibility for generating foreign currency for the country. Therefore, the aim of this project is to carry out bioaccessibility studies of the bioactive constituents p-coumaric acid, artepillin C, baccharin and drupanin of three patented formulations of green propolis extracts, through in vitro tests that are based on the physiology of the gastrointestinal tract and simulate the conditions of human digestion. Next, studies will be carried out to evaluate the intestinal permeability of these constituents in the three formulations in a Caco-2 cell model, recognized by ANVISA as an in vitro method that can replace clinical trials (RDC N¿ 749 of September 5, 2022). In this model, it will also evaluate the effect of the constituents of the formulations on the expression of P-glycoprotein, a plasma membrane protein that may limit oral absorption and cause variability in pharmacokinetic parameters. The occurrence of intestinal metabolism of the bioactive compounds in the formulations will also be investigated and, if metabolites are detected, the compounds that produce metabolites will be submitted to biotransformation studies. Bacteria from the intestinal microbiota and filamentous fungi will be used, aiming to select one or two processes that mimic intestinal metabolism to isolate the metabolites and determine their chemical structures. (AU)