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Abstract Diabetic neuropathy (DN) is a common complication that is associated with diabetic patients. Multiple mechanisms were proposed to have role in the pathophysiology of DN including oxidative stress, inflammation and recently autophagy. Arctigenin (ARC) is a natural lignan isolated from some plants of the Asteraceae family that shows antioxidant property.The present study showed deterioration of the function and structure of neurons as a result of hyperglycaemia. Arctigenin improved the behavioural and histopathological changes of diabetic mice. Arctigenin combated oxidative stress through diminishing lipid peroxidation and improving the activity of antioxidant enzymes. This was concomitant by reducing the biomarkers of apoptosis, activation of autophagy and AMPK pathway. Key words:diabetic neuropathy, AMPK, Arctigenin, Autophagy |