Study of the pharmacokinetic profile of red propolis and its prenylated benzophenones in pre-clinical and clinical models.

• Grant number: 23/15821-1
• Support Opportunities: Scholarships in Brazil - Doctorate (Direct)
• Start date: March 01, 2024
• End date: January 31, 2028
• Field of knowledge: Health Sciences - Pharmacy - Pharmacognosy
• Principal Investigator: Jairo Kenupp Bastos
• Grantee: Matheus Hikaru Tanimoto
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Brazilian red propolis, produced in the coastal region of northeastern Brazil, is a natural productresulting from bees' production of a resinous substance collected from Dalbergiaecastaphyllum and Symphonia globulifera. This product has gained prominence in both thenational and international markets in recent decades due to its numerous pharmacologicalactivities. Among these activities, its cytotoxicity against various cancers, both in vitro and invivo models, has been extensively studied. The obtained results have suggested that this activitymay be partially attributed to the presence of prenylated benzophenones in its composition. Inthis perspective, red propolis can be considered a source of new molecules with potential usein cancer chemoprevention and adjuvant therapies against certain types of cancer. Therefore,chemical and pharmacological studies must ensure safety, efficacy, and quality in developingpotential medications. In this regard, the proposal is to investigate the pharmacokinetic profileof prenylated benzophenones present in red propolis using preclinical and clinical models.Analytical methods will be developed and validated using LC-MS/MS for quantification andobtaining the pharmacokinetic profile of oblongifolin B and guttiferone E benzophenones in amixture with xanthochimol, present in the standardized crude extract of red propolis. In thepreclinical pharmacokinetic assay, 320 male Wistar Hannover rats will be divided into eightgroups (n=40). The compounds will be administered via oral gavage and, subsequently,intravenously. The extracts and isolated substances will be administered as a single dose atconcentrations of 300 mg/kg and 30 mg/kg of body weight, respectively. For the clinical trial,healthy volunteers will visit the Clinical Research Unit (CRU) of HC-FMRP/USP for bloodand urine sample collection. Clinical, physical, and laboratory examinations will be conductedon all volunteers throughout the study period. The benzophenone-rich extract (BRE) dose willbe 10 mg/kg of body weight, administered orally through capsules. The marker fexofenadinewill be administered before and after the last dose of BRE to evaluate its influence on Pglycoprotein (P-gp). If inhibition or induction of this protein is observed, additional studies willbe required. In this case, intestinal permeability assays will be performed using Caco-2 cells toquantify and evaluate the concentrations of benzophenones