In this study, the potential of whey protein hydrolysate (WPH) containing LDIQK peptide and treadmill exercise to prevent cognitive decline was investigated along with the neuroprotective mechanisms. Cognitive dysfunction was induced in mice by 1 mg/kg scopolamine, followed by administration of WPH at 100 and 200 mg/kg and/or treadmill exercise at 15 m/min for 30 min five days per week. Both WPH administration and treadmill exercise significantly improved memory in mice with scopolamine-induced cognitive impairment, which was attributed to several key mechanisms, including a reduction in oxidative stress based on decreased levels of reactive oxygen species and malondialdehyde in the brain tissue and an increase in acetylcholine by increasing choline acyltransferase and decreasing acetylcholine esterase levels. Exercise and WPH also exerted neuroprotective effects by inhibiting the hyperphosphorylation of tau protein, enhancing the expression of brain-derived neurotrophic factor, and inhibiting apoptosis by reducing the Bax/Bcl2 ratio in conjunction with downregulation of the mitogen-activated protein kinase pathway. Moreover, the impact of WPH and treadmill exercise extended to the gut microbiome, suggesting a potential link with cognitive improvement. These findings suggest that both WPH intake and treadmill exercise are effective strategies for mitigating cognitive impairment, providing promising avenues for treating neurodegenerative diseases.

To understand the mechanisms involved in the anti-obesity effects Centella asi-atica (CA), we examined body weight, serum levels, white adipose tissue (WAT) weight, histological analysis, and the expression of cholesterol homeostasis- and lipid metabolism-related genes in mice with high-fat, high-sugar diet (HFHSD)-induced obesity that were orally treated with CA for 12 weeks. Eight-week-old, male C57BL/6J mice were assigned to the following four groups (eight mice/group): NOR, normal diet; Control, HFHSD; CA-L, HFHSD+CA 300 mg/kg; CA-H, HFHSD+CA 600 mg/kg. CA treatment signifi-cantly attenuated HFHSD-induced increase in body weight gain, serum glucose, serum triacylglycerol, and WAT weight (p < 0.05). Compared to that in Control group, adipocyte diameter and macrovesicular area of epididymal WAT signif-icantly decreased with CA treatment (p < 0.05). The mRNA expression levels of peroxisome proliferator-activated receptor gamma (PPARγ), fatty acid synthase (FAS), cluster of differentiation 36 (CD36), 3- hydroxyl-3-methylglutaryl CoA reductase (HMGCR), and stearoyl CoA desaturase 1 (SCD 1) were significantly downregulated in the CA-H group compared to the Control group (p < 0.05). CA exerts anti-obesity effects by lowering body fat accumulation via regulat-ing gene expression in the liver and thus, is a potential lipid-lowering agent.