Synthetic antioxidants are widely used in the food industry. However, the potential toxicity, carcinogenic effects, and possible health damage caused by the ingestion of synthetic compounds, and also consumer concern about the safety of such additives has motivated the food industry to search for natural alternatives. Natural compounds with antioxidant properties are able to retard or prevent lipid oxidation in food. Animal sources like fish, eggs, meats, and dairy products are essential foods for human health due to their lipid fraction with high contents of unsaturated compounds, such as polyunsaturated fatty acids and cholesterol. However, these unsaturated lipids when exposed to favorable factors can become oxidized, which leads to sensory and nutritional losses as well as the formation of oxidized compounds known as cholesterol oxidation products or COPs. COPs are associated with deleterious health effects, such as inflammation, cytotoxicity, atherogenesis, carcinogenesis, and alterations in cell membrane properties, as well as the development of degenerative diseases such as Alzheimer's, Parkinson's, Huntington's, and other chronic diseases. Thus, the use of natural antioxidants can be an alternative to synthetics to prevent the formation of COPs and extend the shelf life of foods susceptible to oxidative deterioration. This review brings together information concerning the use of natural antioxidants as a strategy to control cholesterol oxidation.

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The repurposing strategy was applied herein to evaluate the effects of lopinavir, an aspartic protease inhibitor currently used in the treatment of HIV-infected individuals, on the globally widespread opportunistic human fungal pathogen Candida albicans by using in silico, in vitro and in vivo approaches in order to decipher its targets on fungal cells and its antifungal mechanisms of action. Secreted aspartic proteases (Saps) are the obviously main target of lopinavir. To confirm this hypothesis, molecular docking assays revealed that lopinavir bound to the Sap2 catalytic site of C. albicans as well as inhibited the Sap hydrolytic activity in a typically dose-dependent manner. The inhibition of Saps culminated in the inability of C. albicans yeasts to assimilate the unique nitrogen source (albumin) available in the culture medium, culminating with fungal growth inhibition (IC50 = 39.8 µM). The antifungal action of lopinavir was corroborated by distinct microscopy analyses, which evidenced drastic and irreversible changes in the morphology that justified the fungal death. Furthermore, our results revealed that lopinavir was able to (i) arrest the yeasts-into-hyphae transformation, (ii) disturb the synthesis of neutral lipids, including ergosterol, (iii) modulate the surface-located molecules, such as Saps and mannose-, sialic acid- and N-acetylglucosamine-containing glycoconjugates, (iv) diminish the secretion of hydrolytic enzymes, such as Saps and esterase, (v) negatively influence the biofilm formation on polystyrene surface, (vi) block the in vitro adhesion to epithelial cells, (vii) contain the in vivo infection in both immunocompetent and immunosuppressed mice and (viii) reduce the Sap production by yeasts recovered from kidneys of infected animals. Conclusively, the exposed results highlight that lopinavir may be used as a promising repurposing drug against C. albicans infection as well as may be used as a lead compound for the development of novel antifungal drugs.

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