Ghasemzadeh_2024_Iran.J.Basic.Med.Sci_27_1492

Juglans regia L. (walnut) has a rich history in traditional medicine due to its various medicinal properties, including its neuroprotective effects on nervous system disorders. This updated review sheds light on the therapeutic potential of walnuts in nervous system disorders such as Alzheimer's disease, Parkinson's disease, depression, epilepsy, and pain, supported by evidence from in vivo and in vitro studies. These beneficial effects are attributed to the walnut's rich composition of bioactive compounds, including gallic acid, protocatechuic acid, ferulic acid, sinapate, ellagic acid, p-hydroxybenzoic acid, p-coumaric acid, quercetin 3-galactoside, juglone, vanillic acid, quercetin, myricetin, kaempferol, apigenin, luteolin, daidzein, and others. The mechanisms underlying the neuroprotective effects of walnuts include decreasing oxidative stress, inflammation, apoptosis, proteolysis, beta-amyloid plaque accumulation, acetylcholinesterase (AChE) activity, phosphorylated-c-Jun N-terminal kinase (p-JNK) levels, increasing adenosine triphosphate (ATP) levels, mitochondrial homeostasis, expression of mitophagy-related proteins, and activating the nuclear factor erythroid 2-related factor 2 (Nrf2)/Kelch-like ECH-associated protein 1 (KEAP1)/heme oxygenase-1 (HO-1) pathway. Although walnuts hold great promise in managing nervous system disorders and their complications, further preclinical and clinical investigations are necessary to consolidate these findings. This comprehensive review highlights the potential of walnuts as a natural therapeutic agent and encourages future research to unlock their full neuroprotective potential.