Walnut Oil Reduces Aβ Levels and Increases Neurite Length in a Cellular Model of Early Alzheimer Disease

Abstract

(1) Background: Mitochondria are the cells’ main source of energy. Mitochondrial dysfunction represents a key hallmark of aging and is linked to the development of Alzheimer’s disease (AD). Maintaining mitochondrial function might contribute to healthy aging and the prevention of AD. The Mediterranean diet, including walnuts, seems to prevent age-related neurodegeneration. Walnuts are a rich source of α-linolenic acid (ALA), an essential n3-fatty acid and the precursor for n3-long-chain polyunsaturated fatty acids (n3-PUFA), which might potentially improve mitochondrial function. (2) Methods: We tested whether a lipophilic walnut extract (WE) affects mitochondrial function and other parameters in human SH-SY5Y cells transfected with the neuronal amyloid precursor protein (APP695). Walnut lipids were extracted using a Soxhlet Extraction System and analyzed using GC/MS and HPLC/FD. Adenosine triphosphate (ATP) concentrations were quantified under basal conditions in cell culture, as well as after rotenone-induced stress. Neurite outgrowth was investigated, as well as membrane integrity, cellular reactive oxygen species, cellular peroxidase activity, and citrate synthase activity. Beta-amyloid (Aβ) was quantified using homogenous time-resolved fluorescence. (3) Results: The main constituents of WE are linoleic acid, oleic acid, α-linolenic acid, and γ- and δ-tocopherol. Basal ATP levels following rotenone treatment, as well as citrate synthase activity, were increased after WE treatment. WE significantly increased cellular reactive oxygen species but lowered peroxidase activity. Membrane integrity was not affected. Furthermore, WE treatment reduced Aβ1–40 and stimulated neurite growth. (4) Conclusions: WE might increase ATP production after induction of mitochondrial biogenesis. Decreased Aβ1–40 formation and enhanced ATP levels might enhance neurite growth, making WE a potential agent to enhance neuronal function and to prevent the development of AD. In this sense, WE could be a promising agent for the prevention of AD.

Linolenic acid ameliorates sarcopenia in C. elegans by promoting mitophagy and fighting oxidative stress

“…21,22 In addition, some studies have found that linolenic acid also played a positive role in protecting mitochondrial function, such as regulating mitochondrial biology and mitochondrial dynamics, restoring mitochondrial quality control to improve mitochondrial dysfunction and structural damage. 23–27…”

“…21,22 In addition, some studies have found that linolenic acid also played a positive role in protecting mitochondrial function, such as regulating mitochondrial biology and mitochondrial dynamics, restoring mitochondrial quality control to improve mitochondrial dysfunction and structural damage. [23][24][25][26][27] Based on previous studies, the hypothesis of this study was that the amelioration of sarcopenia by linolenic acid is related to mitochondrial function and oxidative stress. C. elegans is a model animal for screening bioactive components due to its simple feeding, short growth cycle and rapid reproduction.…”

Natural product-based pharmacological studies for neurological disorders

“…The water extract of walnut ( Juglandis semen ) has exhibited pivotal neuroprotective action in various research studies. This extract was found to deplete ROS and NO (nitric oxide) growth, further blocking the loss of DA, thus showing exceptional recovery in patients with PD ( Esselun et al, 2022 ). In another investigation by Yang et al, the walnut-derived polypeptide (TW-7) observed antioxidant action simultaneously initiating autophagy.…”

Caenorhabditis elegans as a Model for the Effects of Phytochemicals on Mitochondria and Aging

“…In addition, polyphenols have protective effects on blood vessels and the heart and can prevent thrombosis [ 122 ]. Anti-cancer and neuroprotective effects have also been described [ 123 , 124 , 125 ] ( Table 1 ).…”