Caracterização e avaliação do potencial antioxidante e hepatoprotetor da castanha, do açaí e da bergenina em modelos in vitro e in vivo

Abstract

Chronic liver diseases, especially Metabolic Fatty Liver Disease-Associated Dysfunction (MASLD), represent one of the major global public health challenges, strongly related to obesity, insulin resistance, and metabolic disorders. Oxidative stress plays a central role in its pathophysiology and progression, promoting inflammation, cell damage, and liver dysfunction. In this context, natural products rich in bioactive compounds have attracted increasing interest due to their ability to modulate oxidative and inflammatory processes. Considering the Amazonian biodiversity as a promising source of these compounds, this study aimed to characterize and evaluate the antioxidant and hepatoprotective potential of Brazil nut (Bertholletia excelsa), açaí (Euterpe precatoria Mart.), and bergenin, alone and in combination with selenium, using in vitro and in vivo experimental models of liver injury and steatosis. To this end, physicochemical analyses, antioxidant assays, cytotoxicity tests, and hepatotoxicity and steatosis models in HEPG-2 cells were performed, in addition to in vivo experiments with liver injury induced by carbon tetrachloride (CCL₄). The extract obtained from Brazil nut kernel residues showed a high content of phenolic compounds (98.3 mg GAE/g) and flavonoids (45.7 mg QE/g), with high antioxidant capacity (DPPH 85.4% and ABTS 88.9%) and absence of significant cytotoxicity in HEPG-2 and MRC-5 cell lines. In a CCL₄ -induced hepatotoxicity model, the extract significantly reduced AST, ALT, ALP, and LDH enzymes, and malondialdehyde (MDA) levels. The lyophilized extract of açaí pulp showed physicochemical properties compatible with amorphous phenolic compounds and good thermal stability. Significant antioxidant activity was demonstrated by DPPH (48.6%), ABTS (59.9%), and ORAC (1122.65 μmol TE/g) assays, without showing relevant cellular toxicity. In fatty acid- induced hepatic steatosis models in HEPG-2 cells, the extract reduced intracellular lipid accumulation in both the prevention and treatment protocols, achieving reductions greater than 50% compared to the control group. Bergenin and selenium were investigated for their antioxidant and hepatoprotective potential, evaluated in relevant experimental models. Analyses indicated positive effects on biochemical and cellular parameters associated with oxidative stress and hepatic steatosis, highlighting the biological potential of the studied compounds. The results obtained reinforce the relevance of these substances as promising candidates for future therapeutic applications, especially in the context of the development of nutraceuticals and phytotherapeutics aimed at preventing liver diseases related to oxidative stress. The study also highlights the importance of Amazonian biodiversity as a strategic source for pharmaceutical innovation.