BIOATIVIDADE DA PUNICALAGINA (Punica granatum) EM MODELO DE SEPSE INDUZIDA EM CAMUNDONGO

Abstract

Sepsis consists of an organic dysfunction arising from an infection that causes an inflammatory response throughout the body. It is considered a serious health problem and one of the 10 most responsible for the number of deaths worldwide. Alternative ways to treat diseases have been studied, such as herbal medicine, which consists of the use of medicines from vegetables or medicinal plants. Punica granatum L., popularly known as Pomegranate, is used as a vermifuge, anthelmintic, antiallergic and in the treatment of urinary tract infections, syphilis, ulcers, diarrhea, among other clinical manifestations. Among its phenolic compounds, punicalagin is largely responsible for these effects. Objectives: to investigate the infant mortality rate due to sepsis in Brazil and the bioactivity of Punica granatum and punicalagin on in vivo sepsis models. Methods: Chapter I – an ecological time series study was carried out and the trend in infant mortality due to sepsis was analyzed using the International Classification of Diseases (ICD10) according to place of residence (North, Northeast, Southeast, South and Central-West ); Chapter II – lethal polymicrobial sepsis was induced in mice using cecal ligation and puncture (CLP), the animals were divided into three groups (Sham – sham-operated, CLP-control – PBS and CLP-HCEPg – single dose, 5 mg /kg, subcutaneous administration), treatment was started immediately after sepsis induction and survival was assessed every 12 hours for five days. Serum levels of cytokines, the number of colony forming units (CFU), as well as such as the number of cells in lymphoid organs and their activation markers; Chapter III - an investigation of punicalagin was carried out in the sepsis infection model and the hematological, histopathological parameters, colony forming units (CFU), cellularity in the blood, lymphoid organs, peritoneal cavity and bronchoalveolar lavage (BAL), production of IL-2, IL-4, IL-6, IFN-γ, TNF-α, IL-17 and IL-10, nitric oxide and statistical differences from all analyzes were considered significant when p < 0.05. Results: Chapter I – most regions showed a decreasing trend in sepsis mortality rates across all age groups, despite regional differences; Chapter II – P. granatum improved the life expectancy of septic mice, possibly due to its antimicrobial, anti-inflammatory and immunomodulatory effects, thus regulating bacterial load and translocation, as well as controlling sepsis-induced systemic inflammation; Chapter III – punicalagin associated with an antibiotic exerted an antimicrobial and immunomodulatory effect on mice with sepsis. Conclusions: mortality rates from sepsis are mostly decreasing in Brazil, P. granatum and punicalagin associated with antibiotics are interesting alternatives for the treatment of septic individuals.