hyperoside and Cognitive-Dysfunction

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.. Streptozotocin/high-fat diet-induced diabetic rats were treated orally with HYP (50, 200 and 400 mg/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-κB), tumour necrosis factor-alpha (TNF-α), interleukin-1β (IL-1β) 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.. 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-1β, IL-6, TNF-α, NF-κB, caspase-3 and MDA were prominently increased. Interestingly, the HYP treatment dose-dependently abrogated the altered cognitive and biochemical parameters.. The results suggested that hyperoside prevents DM-induced cognitive dysfunction, neuroinflammation and oxidative stress via antioxidant, anti-inflammatory and antiapoptotic mechanisms in rats.

Topics: Acetylcholinesterase; Animals; Anti-Inflammatory Agents; Antioxidants; Caspase 3; Cognitive Dysfunction; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Hippocampus; Interleukin-6; Neuroinflammatory Diseases; NF-kappa B; Oxidative Stress; Quercetin; Rats; Superoxide Dismutase; Tumor Necrosis Factor-alpha

Alzheimer's disease (AD) is a highly prevalent neurodegenerative disorder characterized by the pathological hallmarks of β-amyloid plaque deposits, tau pathology, inflammation, and cognitive decline. Hyperoside, a flavone glycoside isolated from Rhododendron brachycarpum G. Don (Ericaceae), has neuroprotective effects against Aβ both in vitro and in vivo. However, whether hyperoside could delay AD pathogenesis remains unclear. In the present study, we observed if chronic treatment with hyperoside can reverse pathological progressions of AD in the APP/PS1 transgenic mouse model. Meanwhile, we attempted to elucidate the molecular mechanisms involved in regulating its effects. After 9 months of treatment, we found that hyperoside can improve spatial learning and memory in APP/PS1 transgenic mice, reduce amyloid plaque deposition and tau phosphorylation, decrease the number of activated microglia and astrocytes, and attenuate neuroinflammation and oxidative stress in the brain of APP/PS1 mice. These beneficial effects may be mediated in part by influencing reduction of BACE1 and GSK3β levels. Hyperoside confers neuroprotection against the pathology of AD in APP/PS1 mouse model and is emerging as a promising therapeutic candidate drug for AD.

Topics: Alzheimer Disease; Amyloid beta-Peptides; Amyloid Precursor Protein Secretases; Animals; Aspartic Acid Endopeptidases; Cognitive Dysfunction; Disease Models, Animal; Mice, Transgenic; Neuroprotective Agents; Plaque, Amyloid; Quercetin; Time