Walnut Prevents Cognitive Impairment by Regulating the Synaptic and Mitochondrial Dysfunction via JNK Signaling and Apoptosis Pathway in High-Fat Diet-Induced C57BL/6 Mice

Abstract

This study was conducted to evaluate the protective effect of Juglans regia (walnut, Gimcheon 1ho cultivar, GC) on high-fat diet (HFD)-induced cognitive dysfunction in C57BL/6 mice. The main physiological compounds of GC were identified as pedunculagin/casuariin isomer, strictinin, tellimagrandin I, ellagic acid-O-pentoside, and ellagic acid were identified using UPLC Q-TOF/MS analysis. To evaluate the neuro-protective effect of GC, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), 2′,7′-dichlorodihydrofluorecein diacetate (DCF-DA) analysis were conducted in H2O2 and high glucose-induced neuronal PC12 cells and hippocampal HT22 cells. GC presented significant cell viability and inhibition of reactive oxygen species (ROS) production. GC ameliorated behavioral and memory dysfunction through Y-maze, passive avoidance, and Morris water maze tests. In addition, GC reduced white adipose tissue (WAT), liver fat mass, and serum dyslipidemia. To assess the inhibitory effect of antioxidant system deficit, lipid peroxidation, ferric reducing antioxidant power (FRAP), and advanced glycation end products (AGEs) were conducted. Administration of GC protected the antioxidant damage against HFD-induced diabetic oxidative stress. To estimate the ameliorating effect of GC, acetylcholine (ACh) level, acetylcholinesterase (AChE) activity, and expression of AChE and choline acetyltransferase (ChAT) were conducted, and the supplements of GC suppressed the cholinergic system impairment. Furthermore, GC restored mitochondrial dysfunction by regulating the mitochondrial ROS production and mitochondrial membrane potential (MMP) levels in cerebral tissues. Finally, GC ameliorated cerebral damage by synergically regulating the protein expression of the JNK signaling and apoptosis pathway. These findings suggest that GC could provide a potential functional food source to improve diabetic cognitive deficits and neuronal impairments.

Ellagitannins from Eucalyptus camaldulensis and their potential use in the food industry

“…Within the Eucalyptus genus, it has been mentioned that they are high in ellagitannins among they are tellimagrandin I, with high antioxidant potential, as is E. globulus with extracts, where the presence of ellagitannins is higher and gives it activity [76]. Furthermore, in extracts of Plinia cauliflora, showed a DPPH inhibitory concentration (IC 50 ) of 1.45 µg/mL ± 0.02 µg/mL, as well as a peroxidation inhibition greater than 70% [77].…”

Editorial: A Feasible Approach for Natural Products to Treatment of Diseases

“…In another combined in vivo and in vitro experiment, Moon et al [4] showed that walnuts (Juglans regia) could be a potential functional food to improve diabetic cognitive deficits and neuronal impairments. The study found evidence that walnuts inhibit reactive oxygen species production in high-glucose-induced neuronal and hippocampal cells and ameliorate behavioral and memory dysfunction in mice with cognitive impairment induced by a high fat diet.…”