EFEITOS ANTIOXIDANTES DOS COMPOSTOS FENÓLICOS E INVESTIGAÇÃO DO POTENCIAL ANTIOXIDANTE DE Zingiber officinale EM Caenorhabditis elegans: revisão sistemática e análise in vivo.

Abstract

Natural products are increasingly being studied for the treatment and prevention of various pathologies, such as those involving redox imbalance. In this context, Zingiber officinale (ginger) stands out. It is a plant species widely used worldwide and included in the National List of Medicinal Plants of Interest to the Unified Health System (SUS), due to its high pharmacological potential (antioxidant, anti-inflammatory, and antiemetic activities already described). These properties have been associated with the rich phytochemical composition of this species, particularly its rhizome, which is composed of bioactive compounds, particularly gingerols. Traditionally, preclinical studies of these products are conducted in rodents. However, considering the need to comply with the bioethical principles of the 3Rs, alternative methods for conducting experimental studies are necessary. Thus, Caenorhabditis elegans has proven to be a powerful tool for conducting various studies, as it exhibits genes and signaling pathways similar to those of humans. Therefore, the objective of this project is to compile evidence of the antioxidant effect of phenolic compounds and evaluate the antioxidant activity of Z. officinale in C. elegans. In the systematic review, 37 studies testing the antioxidant activity of phenolic compounds using this alternative model were selected. Among the studies, 61 substances were tested, and 46 showed promise, with reduced ROS and/or increased antioxidant enzymes. The most frequently mentioned larval stage was L4, with chronic exposure. The tests to determine the antioxidant activity of the compounds included determination of reactive oxygen species (ROS) and quantification of the antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GSH), and malonaldehyde (MDA). In the experimental phase, ginger was purchased at a street market to obtain the crude extract by liquid-liquid partitioning, the gingerol-rich fraction by thin-layer chromatography, and 6-gingerol by high-performance liquid chromatography coupled to a mass spectrometer and nuclear magnetic resonance. To evaluate antioxidant activity, C. elegans were exposed to the gingerol-rich fraction (0.25, 0.5, 1, 2, and 4 mg/mL) and subjected to determination of survival rate, heat stress, and ROS generation. The worms survived at all predefined concentrations of the gingerol-rich fraction. Furthermore, greater resistance to heat stress and a decrease in ROS were observed in the worms exposed to the substrate compared to the unexposed control group. Thus, the results obtained suggest that phenolic compounds exhibit antioxidant activity in C. elegans, and consequently, ginger also exhibits such activity. Thus, phenolic compounds and gingerols can influence/improve various pathologies that are related to redox imbalance.