Oligonol enhances brain cognitive function in high-fat diet-fed mice.

Oligonol, a low-molecular-weight polyphenol derived from lychee fruit, is well recognized for its antioxidant properties, blood glucose regulation, and fat mass reduction capability. However, its effect on the central nervous system remains unclear. Here, we investigated the effects of oligonol on brain in a high-fat diet (HFD) fed mouse model, and SH-SY5Y neuronal cells and primary cultured cortical neuron under insulin resistance conditions. HFD mice were orally administered oligonol (20 mg/kg) daily, and SH-SY5Y cells and primary cortical neurons were pretreated with 500 ng/mL oligonol under in vitro insulin resistance conditions. Our findings revealed that oligonol administration reduced blood glucose levels and improved spatial memory function in HFD mice. In vitro data demonstrated that oligonol protected neuronal cells and enhanced neural structure against insulin resistance. We confirmed RNA sequencing in the oligonol-pretreated insulin-resistant SH-SY5Y neuronal cells. Our RNA-sequencing data indicated that oligonol contributes to metabolic signaling and neurite outgrowth. In conclusion, our study provides insights into therapeutic potential of oligonol with respect to preventing neuronal cell damage and improving neural structure and cognitive function in HFD mice.