Effects of different doses of resveratrol on central carbon metabolic pathways and cytokine-mediated signaling networks in rats

Resveratrol, as a popular research substance, is favoured for its health-promoting, anti-aging and immunomodulatory properties. In order to further reveal the immune function of resveratrol as well as the immunomodulatory mechanism, in the present study, formulated low, medium and high doses of resveratrol solutions were administered by gavage to healthy male rats. Twenty-seven serum cytokines, glucose, lactate, nicotinamide adenine dinucleotide (NADH) and 13 metabolic enzymes were detected, and the cytokine-mediated signaling network and metabolic network were constructed and the correlation analysis between the two networks was performed. The results showed that the two experimental groups of low and medium resveratrol presented the results of reduced catabolism and enhanced anabolism, which were most significant in the low-dose group and enhanced catabolism in the high-dose group. Among them, the low dose of resveratrol significantly increased the rate of change in the concentration of pro-inflammatory cytokines IL-1β and chemokine LIX, significantly decreased the rate of change in the concentration of chemokine MCP-1, and significantly decreased the rate of change in the concentration of phosphofructokinase (PFK), glyceraldehyde dehydrogenase 3-phosphate (GAPDH), pyruvate dehydrogenase complex (PDHC), α-keto glutarate dehydrogenase (α-KGDHC), and very significantly elevated the expression of isocitrate dehydrogenase (IDH) and malate dehydrogenase (MDH). Overall, low dose of resveratrol may be more beneficial in combating metabolic disorders. Moreover, multiple cytokines and enzymes showed significant strong correlations, i.e., different doses of resveratrol regulated the entire metabolic network by altering the rate of synthesis and secretion of cytokines/chemokines, which in turn altered the transcription and expression of enzymes in the central carbon metabolic pathway.