Chen_2021_Nutr.Neurosci__1

OBJECTIVES: Literature findings have instituted the role of hyperglycemia-induced oxidative stress and inflammation in the pathogenesis of cognitive derangement in diabetes mellitus (DM). Hyperoside (HYP) is a flavanone glycoside reported to possess diverse pharmacological benefits such as antioxidant and anti-inflammatory properties. The study explored whether HYP could mitigate DM-induced cognitive dysfunction and further elucidate on potential molecular mechanism in rats. METHODS: Streptozotocin/high-fat diet-induced diabetic rats were treated orally with HYP (50, 200 and 400mg/kg/day) for six consecutive weeks. The blood glucose and serum insulin levels, Morris water maze test, intraperitoneal glucose tolerance test, and brain acetylcholinesterase (AChE) activity were determined. The brain expression of inflammatory nuclear factor-kappa B (NF-kappaB), tumour necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta) and interleukin-6 (IL-6), as well as superoxide dismutase (SOD), catalase (CAT), reduced glutathione (GSH), total antioxidant capacity (TAC), malondialdehyde (MDA), lipid profile and caspase-3 activity were estimated. RESULTS: DM evoked hyperlipidemia, hypoinsulinemia, cognitive dysfunction by markedly increased AChE and reduction in learning and memory capacity. Brain activities of SOD and CAT, and levels of TAC and GSH were considerably depressed, whereas levels of IL-1beta, IL-6, TNF-alpha, NF-kappaB, caspase-3 and MDA were prominently increased. Interestingly, the HYP treatment dose-dependently abrogated the altered cognitive and biochemical parameters. DISCUSSION: The results suggested that hyperoside prevents DM-induced cognitive dysfunction, neuroinflammation and oxidative stress via antioxidant, anti-inflammatory and antiapoptotic mechanisms in rats.