No abstract

Autophagy flux plays a significant protective role in type 2 diabetes mellitus (T2DM). However, the mechanisms by which autophagy mediates insulin resistance (IR) to ameliorate T2DM remain unclear. This study explored the hypoglycemic effects and mechanisms of walnut-derived peptides (fraction 3−10 kDa and LP5) in streptozotocin and high-fat-diet-induced T2DM mice. Findings revealed that walnut-derived peptides reduced the levels of blood glucose and FINS and ameliorated IR and dyslipidemia. They also increased SOD and GSH-P X activities and inhibited the secretion of TNF-α, IL-6, and IL-1β. Additionally, they increased the levels of ATP, COX, SDH, and MMP of liver mitochondria. Western blotting indicated that walnut-derived peptides upregulated LC3-II/LC3-I and Beclin-1 expression, while they down-regulated p62 expression, which may be associated with the activation of the AMPK/mTOR/ULK1 pathway. Finally, the AMPK activator (AICAR) and inhibitor (Compound C) were used to verify that LP5 could activate autophagy through the AMPK/mTOR/ULK1 pathway in IR HepG2 cells.

This work aimed to investigate whether there are synergistic effects between walnut peptide (WNP) and ginseng extracts (GSE) treatments to ameliorate the memory impairment caused by scopolamine (SCOP). The Morris water maze trial, hippocampal neuron morphology, neurotransmitters, and synaptic ultrastructure were examined, along with brain-derived neurotrophic factor (BDNF)-related signaling pathway proteins. The results of the Morris water maze trial demonstrated that the combined administration of WNP and GSE effectively alleviated memory impairment in C57BL/6 rats caused by SCOP. Improvement in the morphology of hippocampal neurons, dendritic spines, and synaptic plasticity and upregulation of neurotransmitters AChE, ACh, ChAT, Glu, DA, and 5-HT supported the memory improvement effects of WNP + GSE. In addition, compared with the model group, WNP + GSE significantly enhanced the protein levels of VAChT, Trx-1, and the CREB/BDNF/TrkB pathway in hippocampal and PC12 cells induced by SCOP (p < 0.05). Notably, WNP + GSE boosted memory via multiple pathways, not only the BDNF/TrkB/CREB target.