Curcumin, Polydatin and Quercetin Synergistic Activity Protects from High-Glucose-Induced Inflammation and Oxidative Stress

Chronic hyperglycemia, the diagnostic biomarker of Type 2 Diabetes Mellitus (T2DM), is a condition that fosters oxidative stress and proinflammatory signals, both involved in the promotion of cellular senescence. Senescent cells acquire a proinflammatory secretory phenotype, called SASP, exacerbating and perpetuating the detrimental effects of hyperglycemia. Bioactive compounds can exert antioxidant and anti-inflammatory properties. However, the synergistic anti-inflammatory and antioxidant effects of the most extensively investigated natural compounds have not been confirmed yet in senescent cells and in hyperglycemic conditions. Here, we exposed young and replicative senescent HUVEC (yHUVEC and sHUVEC) to a high-glucose (HG) condition (45 mM) and treated them with Polydatin (POL), Curcumin (CUR) and Quercetin (QRC), alone or in combination (MIX), to mirror the anti-inflammatory component OxiDef (TM) contained in the novel nutraceutical GlicefenTm (Mivell, Italy). In both yHUVEC and sHUVEC, the MIX significantly decreased the expression levels of inflammatory markers, such as MCP-1, IL-1 beta and IL-8, and ROS production. Importantly, in sHUVEC, a synergistic effect of the MIX was observed, suggesting its senomorphic activity. Moreover, the MIX was able to reduce the expression level of RAGE, a receptor involved in the activation of proinflammatory signaling. Overall, our data suggest that the consumption of nutraceuticals containing different natural compounds could be an adjuvant supplement to counteract proinflammatory and pro-oxidative signals induced by both hyperglycemic and senescence conditions.

Automated summary

Chronic hyperglycemia, a diagnostic biomarker of Type 2 Diabetes Mellitus (T2DM), promotes oxidative stress and proinflammatory signals, which contribute to cellular senescence. Despite extensive research, the synergistic anti-inflammatory and antioxidant effects of natural compounds in senescent cells and hyperglycemic conditions have not been confirmed. In this study, a mixture of natural compounds significantly decreased the expression of inflammatory markers in both young and replicative senescent cells, suggesting a senomorphic activity. This research highlights the potential of nutraceuticals as adjuvant supplements to counteract proinflammatory and pro-oxidative signals induced by hyperglycemia and senescence.