Avaliação do potencial biotecnológico de uma bebida do tipo kombucha a base própolis vermelha amazônica e mel de tiúba in vitro e in vivo

Abstract

Plant-based fermented beverages have gained relevance as functional foods, particularly due to their sensory acceptance and health-promoting potential. In this context, kombucha stands out as a versatile fermentative matrix, whose bioactive metabolites can be enhanced by the incorporation of ingredients with specific therapeutic properties, such as Amazonian red propolis and tiúba honey, both widely recognized in ethnomedicine for their antioxidant, antimicrobial, and immunomodulatory effects. Despite this potential, the synergistic effect of this formulation in modulating immune responses in septic conditions has not yet been elucidated. Therefore, this study aimed to investigate the immunomodulatory, antimicrobial, and anti-inflammatory effects of a kombucha beverage enriched with Amazonian red propolis and tiúba honey, using in vitro assays to assess cytotoxicity and nitric oxide production in macrophages, as well as an in vivo sepsis model to analyze bacterial load, hematological parameters, cytokine profile, and immune phenotyping by flow cytometry. This dissertation was structured into two chapters. Chapter I presents an integrative literature review entitled “Therapeutic Potential of Propolis Against Endotoxemia and infection: Bioactive Properties and in vivo Evidence”. The review discusses the main mechanisms of action and analytical approaches reported in studies indexed in MEDLINE (PubMed), Web of Science, Scopus, ScienceDirect, and Embase. The findings indicate that propolis may represent a promising alternative for modulating the inflammatory response associated with sepsis, as its bioactive compounds have shown potential to reduce pro-inflammatory cytokine production and improve survival in animal models. Chapter II presents the original research article entitled “Evaluation of the Immunomodulatory, Antimicrobial, and Anti-inflammatory Potential of a Kombucha Beverage Based on Amazonian Red Propolis and Tiúba Honey for the Treatment of Sepsis”, which reports the experimental results obtained throughout the project. The kombucha formulation demonstrated low cytotoxicity and a significant reduction in nitric oxide production in vitro. In vivo treatment markedly reduced peritoneal bacterial load and inflammatory cellularity in the bone marrow and peritoneal cavity. Hematological analysis indicated a reduction in total leukocytes and segmented granulocytes. Additionally, the beverage increased levels of IFN-γ, IL-2, IL-4, IL-10, and IL-17A, promoted CD4+ lymphocyte expansion, and modulated CD4+CD3− and CD11c+ subpopulations, suggesting a balanced modulation of innate and adaptive immune responses. Collectively, the findings demonstrate that kombucha enriched with Amazonian red propolis and tiúba honey exerts multifactorial immunomodulatory, antimicrobial, and anti-inflammatory effects in a sepsis model, supporting its potential as an adjuvant therapeutic approach for sepsis management.