Huperzine A Ameliorates Cognitive Deficits in Streptozotocin-Induced Diabetic Rats

Abstract

The present study was designed to probe the effects of Huperzine A (HupA) on diabetes-associated cognitive decline (DACD) using a streptozotocin (STZ)-injected rat model. Diabetic rats were treated with HupA (0.05 and 0.1 mg/kg) for seven weeks. Memory functions were evaluated by the water maze test. Nissl staining was selected for detecting neuronal loss. Protein and mRNA levels of brain-derived neurotrophic factor (BDNF) were analyzed by ELISA and real-time PCR, respectively. The activities of choline acetylase (ChAT), Acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), catalase (CAT), NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 were measured using corresponding kits. After seven weeks, diabetic rats exhibited remarkable reductions in: body weight, percentage of time spent in target quadrant, number of times crossing the platform, ChAT and BDNF levels, SOD, GSH-Px and CAT accompanied with increases in neuronal damage, plasma glucose levels, escape latency, mean path length, AChE, MDA level as well as CAT, NF-κB p65 unit, TNF-α, IL-1β, IL-6 and caspase-3 in cerebral cortex and hippocampus. Supplementation with HupA significantly and dose-dependently reversed the corresponding values in diabetes. It is concluded that HupA ameliorates DACD via modulating BDNF, oxidative stress, inflammation and apoptosis.

Edaravone injection ameliorates cognitive deficits in rat model of Alzheimer’s disease

“…These data indicate that edaravone inhibits AChE and ChAT to modulate cholinergic dysfunction and improve cognitive deficits. Consistent with our results, recent studies suggested that the improvement of cognitive deficits was associated the inhibition of AChE in the mouse and rat models [15,16]. In addition, a recent study demonstrated that oxidative stress was involved in the cognitive impairment in AD [17].…”

Programming Apoptosis and Autophagy with Novel Approaches for Diabetes Mellitus

“…Advanced glycation end products (AGEs), entities that promote complications in DM (32, 36), also result in the release of reactive oxygen species (ROS) and caspase activation (74). In experimental cell models, exposure to elevated glucose levels foster oxidant stress mechanisms that lead to cell injury in cardiomyocytes (35, 39, 102), neurons (55, 63, 69, 103, 104), and endothelial cells (62, 65–68, 105). Elevations in serum glucose also can increase antioxidant enzyme levels in human endothelial cells, suggesting that some cells can attempt a reparative process during oxidative stress exposure (106).…”

“…Since the early phase of apoptosis with membrane PS externalization alerts inflammatory cells to engulf and remove injured cells, prevention of membrane PS externalization is vital to block the loss of functional cells that may become temporarily disabled (21). In DM, apoptosis can lead to neuronal injury (60, 103, 104, 133), cardiomyocyte destruction (34, 35, 38), pancreatic β-cell loss (134–136), endothelial cell injury (25, 26, 67, 105, 137), and renal cell dysfunction (138–140). …”

“…As a result, recent investigations have concentrated upon pathways that involve anti-oxidant therapies (3, 23, 27, 30, 53, 71, 75), mammalian forkhead transcription factors (9, 37, 47, 150, 151), protein tyrosine phosphatases (6, 15, 152), and growth factors (11–13, 50, 65, 70, 104). In addition, new therapeutic strategies are now focusing upon the role of extracellular matrix associated proteins such as the CCN family of proteins (153, 154).…”

Meta-analysis on the association between CYP2D6*10 gene polymorphism and disease free survival of breast cancer patients receiving tamoxifen treatment in Asia

“…15 studies were eliminated for duplicated publications. Finally full-text papers of 9 studies (Cai et al, 2014;Huang et al, 2013;Malarde et al, 2014;Mao et al, 2014;Saracoglu et al, 2012;Wang et al, 2014;Wang et al, 2013;Zhu et al, 2007) were searched from all the citations. A flow chart described the search method and study chose ( Figure 1).…”