Atherosclerosis and cognitive impairment are both influenced by hyperlipidemia. Due to their high margin of safety and low cost, natural chemicals have recently attracted particular attention in the context of the treatment of disease. Hence, the purpose of this study was to investigate the possible amendatory impact of ethanol extract walnut (Juglans regia) seed coat (E‐WSC) on some metabolic enzymes (glutathione reductase (GR), paraoxonase‐1 (PON1), aldose reductase (AR), sorbitol dehydrogenase (SDH), acetylcholinesterase (AChE), glutathione S‐transferase (GST), and butyrylcholinesterase (BChE)) activity in the liver, kidney, and heart of rats with Triton WR‐1339‐induced hyperlipidemia. Rats were divided into five groups: control group, HL‐Control group (Triton WR‐1339 400 mg/kg, i.p administered group), E‐ WSC + 150 (150 mg/kg,o.d given group), E‐ WSC + 300 (E‐ WSC 300 mg/kg, o.d given group) and HL+ E‐WSC + 300 (Group receiving E‐ WSC 300 mg/kg, o.d 30 min prior to administration of Triton WR‐1339 400 mg/kg, i.p). In HL‐Control, AR, SDH, and BChE enzyme activity was significantly increased in all tissues compared to the control, while the activity of other studied enzymes was significantly decreased. The effects of hyperlipidemia on balance were improved and alterations in the activity of the investigated metabolic enzymes were prevented by E‐WSC. As a result, promising natural compounds that can be used as adjuvant therapy in the treatment of cognitive disorders and hyperlipidemia may be found in E‐WSC powder.

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Reactive oxygen species (ROS) including free radicals such as hydroxyl radicals (OH • ), singlet oxygen ( 1 O 2 ), superoxide anion radicals (O 2•-), and non-free radical species such as hydrogen peroxide (H 2 O 2 ) are diverse kinds of activated oxygen and mostly produced by exogenous factors or oxidation product of biological reactions [1][2][3] . ROS have created considerable interest among scientists in the recent years [4][5][6] . Their wide range of effects that are of medicinal and biological interest have led to several experimental studies [7][8][9] . Additionally, it is well-known that ROS induce oxidative damage to biomolecules such as lipids, proteins, carbohydrates and deoxyribonucleic acids [10][11][12] , which might induce cancer, ageing, and other multitude of diseases [13][14][15][16] . In addition, ROS has also been implicated in more than 100 diseases such as heart disease, acquired immunodeficiency syndrome, malaria, stroke, diabetes, arteriosclerosis, and cancer [17][18][19][20] .The plant kingdom, including medicinal and dietary plants, offers many natural phytochemicals that include phenolic diterpenes, triterpenes, flavonoids, phenolic acids and sterols [21][22][23] . Antiinflammatory, antioxidant and anticancer activities reported to be possessed by these compounds might have resulted from prevention of oxidative damage [24,25] . There is rising interest in endemic species because these can be used for preparing phytopharmaceuticals with considerable antioxidant potential or for the production of raw materials and health confidants [26][27][28] . Antioxidant compounds are molecules that can inhibit or delay the oxidation of lipids or other biomolecules by inhibiting the initiation and propagation of oxidative chain reactions [29] . Some plants synthesize large amounts of vitamin C, vitamin E, and carotenoids, which are well-known antioxidants [30][31][32][33] . Phenolic compounds are also widely distributed in plants and have been found to possess antioxidative potential as well [34] . Natural