Sphingolipid Levels and Signaling via Resveratrol and Antioxidant Actions in Cardiometabolic Risk and Disease

Resveratrol (RSV) is a phenolic compound with strong antioxidant activity, which is generally associated with the beneficial effects of wine on human health. All resveratrol-mediated benefits exerted on different systems and pathophysiological conditions are possible through resveratrol's interactions with different biological targets, along with its involvement in several key cellular pathways affecting cardiometabolic (CM) health. With regard to its role in oxidative stress, RSV exerts its antioxidant activity not only as a free radical scavenger but also by increasing the activity of antioxidant enzymes and regulating redox genes, nitric oxide bioavailability and mitochondrial function. Moreover, several studies have demonstrated that some RSV effects are mediated by changes in sphingolipids, a class of biolipids involved in a number of cellular functions (e.g., apoptosis, cell proliferation, oxidative stress and inflammation) that have attracted interest as emerging critical determinants of CM risk and disease. Accordingly, this review aimed to discuss the available data regarding the effects of RSV on sphingolipid metabolism and signaling in CM risk and disease, focusing on oxidative stress/inflammatory-related aspects, and the clinical implications of this relationship.

Automated summary

Resveratrol, a phenolic compound found in wine, exhibits strong antioxidant activity and has beneficial effects on human health. Its interactions with various biological targets and involvement in key cellular pathways affecting cardiometabolic (CM) health contribute to these benefits. Resveratrol functions as an antioxidant by scavenging free radicals, increasing antioxidant enzyme activity, regulating redox genes, nitric oxide bioavailability, and mitochondrial function. Additionally, studies have shown that resveratrol affects sphingolipid metabolism and signaling, which play critical roles in CM risk and disease by influencing apoptosis, cell proliferation, oxidative stress, and inflammation. This review focuses on discussing the effects of resveratrol on sphingolipids in CM and explores the clinical implications of this relationship.