EFFECT OF A GREEN BRAZILIAN PROPOLIS EXTRACT ON THE INHIBITION OF NLRP3 AND NLRP6 INFLAMMASOMES IN STIMULATED HEPATIC STELLATE CELLS WITH SOLUBLE ANTIGENS FROM Schistosoma mansoni EGGS

• Grant number: 24/03616-7
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): July 01, 2024
• Effective date (End): June 30, 2025
• Field of knowledge: Biological Sciences - Parasitology - Helminthology of Parasites
• Principal Investigator: Lizandra Guidi Magalhães
• Grantee: Larissa Crystine Ferreira Costa
• Host Institution: Pró-Reitoria Adjunta de Pesquisa e Pós-Graduação. Universidade de Franca (UNIFRAN). Franca , SP, Brazil

Abstract

Schistosomiasis, caused by the parasite Schistosoma mansoni, is an acute and chronic disease that leads to the continuous formation of granulomas in response to soluble antigens from the parasite's eggs (SEA - soluble egg antigens) in the host's liver. The activation of NLRP3 and NLRP6 inflammasomes (nucleotide-binding domain and leucine-rich repeat receptors) in hepatic cells, notably hepatic stellate cells (HSCs), results in increased regulation of transcription factors such as TGF-1² and NF-ºB, promoting collagen accumulation and the release of inflammatory cytokines such as IL-1² and IL-18, which are crucial for fibrinogenesis processes. In the therapeutic context, Brazilian green propolis (BGP) stands out for its anti-inflammatory and hepatoprotective properties. Previous studies have demonstrated the ability of Brazilian green propolis extract (BGP extract) to inhibit NLRP3, TGF-1², and IL-1² in murine macrophages.Therefore, this study proposes to evaluate in vitro the inhibitory potential of BGP extract on NLRP3 and NLRP6 inflammasomes in the GRX cell line, representative of murine HSCs, after stimulation with SEA. To achieve this, the cytotoxic evaluation of the BGP extract on the GRX cell line will be conducted to determine the concentrations to be assessed. Subsequently, GRX cells will be stimulated with SEA, incubated with or without BGP extract, and the inhibitory effect will be assessed by measuring cytokine levels in the culture supernatant, as well as determining the expression of NLRP3 and NLRP6 proteins, caspase-1, and IL-1² in the cell lysate