Anti-amyloidogenic properties of an ethyl acetate fraction from Actinidia arguta in Aß1-42-induced ICR mice.

This study aimed to investigate the ameliorating effect of an ethyl acetate fraction from the fruit Actinidia arguta (EFAA) on amyloid beta (Aß)-induced neurotoxicity and cognitive deficits in ICR mice. EFAA showed potent protective effects against Aß-induced neurotoxicity through 2',7'-dichlorofluorescein diacetate (DCF-DA), 2',3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) and lactate dehydrogenase (LDH) release into the assay medium. EFAA treatment reduced the intracellular ROS level and lactate dehydrogenase (LDH) release in the mitochondria, and increased cell viability in Aß-induced neuroblastoma MC-IXC cells. The administration of EFAA significantly attenuated Aß-induced learning and memory deficits, which were evaluated by Y-maze, passive avoidance, and Morris water maze tests. Furthermore, EFAA showed the ameliorating effect of cholinergic functions by increasing acetylcholine (ACh) levels and decreasing acetylcholinesterase (AChE) activity, and protected antioxidant systems by increasing superoxide dismutase (SOD) and decreasing the oxidized glutathione (GSH)/total GSH and malondialdehyde (MDA) in the brain. Finally, EFAA prevented mitochondrial dysfunction via regulating apoptotic signaling molecules including phosphorylated Akt (p-Akt), phosphorylated tau (p-tau), Bax, and cytochrome c in the brain tissues. Therefore, the present study suggests that EFAA might be a potential source of natural antioxidants with the ability to ameliorate Aß-induced amnesia.

Cognitive Function of Artemisia argyi H. Fermented by Monascus purpureus under TMT-Induced Learning and Memory Deficits in ICR Mice.

The cognitive effect of Artemisia argyi H. under liquid-state fermentation by Monascus purpureus (AAFM), which has cellular antioxidant activity and neuronal cell viability, on trimethyltin- (TMT-) induced learning and memory impairment in Institute of Cancer Research (ICR) mice was confirmed. Tests were conducted to determine the neuroprotective effects against H2O2-induced oxidative stress, and the results showed that AAFM has protective effects through the repression of mitochondrial injury and cellular membrane damage against H2O2-induced neurotoxicity. In animal experiments, such as the Y-maze, passive avoidance, and Morris water maze tests, AAFM also showed excellent ameliorating effects on TMT-induced cognitive dysfunction. After behavioral tests, brain tissues were extracted to assess damage to brain tissue. According to the experimental results, AAFM improved the cholinergic system by upregulating acetylcholine (ACh) contents and inhibiting acetylcholinesterase (AChE) activity. AAFM effectively improved the decline of the superoxide dismutase (SOD) level and the increase of the oxidized glutathione (GSH) ratio and lipid peroxidation (malondialdehyde (MDA) production) caused by TMT-induced oxidative stress. The occurrence of mitochondrial dysfunction and apoptosis was also decreased compared with the TMT group. Finally, quinic acid derivatives were identified as the major phenolic compounds in AAFM using ultra-performance liquid chromatography quadrupole-time-of-flight (UPLC-Q-TOF) MS analysis.

Ginsenoside Re Ameliorates Brain Insulin Resistance and Cognitive Dysfunction in High Fat Diet-Induced C57BL/6 Mice.

The ameliorating effects of ginsenoside Re (G Re) on high fat diet (HFD)-induced insulin resistance in C57BL/6 mice were investigated to assess its physiological function. In the results of behavioral tests, G Re improved cognitive dysfunction in diabetic mice using Y-maze, passive avoidance, and Morris water maze tests. G Re also significantly recovered hyperglycemia and fasting blood glucose level. In the results of serum analysis, G Re decreased triglyceride (TG), total cholesterol (TCHO), low-density lipoprotein cholesterol (LDLC), glutamic-oxaloacetic transaminase (GOT), and glutamic-pyruvic transaminase (GPT) and increased the ratio of high-density lipoprotein cholesterol (HDLC). G Re regulated acetylcholine (ACh), acetylcholinesterase (AChE), malondialdehyde (MDA), superoxide dismutase (SOD), and oxidized glutathione (GSH)/total GSH by regulating the c-Jun N-terminal protein kinase (JNK) pathway. These findings suggest that G Re could be used to improve HFD-induced insulin resistance condition by ameliorating hyperglycemia via protecting the cholinergic and antioxidant systems in the mouse brains.

Anti-amnesic effect of Dendropanax morbifera via JNK signaling pathway on cognitive dysfunction in high-fat diet-induced diabetic mice.

The ameliorating effects of the ethyl acetate fraction from Dendropanax morbifera (EFDM) on cognitive impairment in high-fat diet (HFD)-induced diabetic mice were examined by measuring its possible pharmacological activities. Administration of EFDM (20 and 50mg/kg body weight) in HFD-induced diabetic mice significantly improved glucose tolerance status in the intraperitoneal glucose tolerance test (IPGTT). In animal experiments using Y-maze, passive avoidance and Morris water maze tests, the cognitive and behavioral disorders in HFD-induced diabetic mice were considerably recovered by regulating cholinergic systems, including acetylcholine (ACh) levels and acetylcholinesterase (AChE) inhibition, and antioxidant systems, including superoxide dismutase (SOD), glutathione (GSH), oxidized GSH, and malondialdehyde (MDA) levels. Furthermore, HFD-induced abnormal activity of mitochondria were also significantly protected by the improvement of the c-Jun N-terminal protein kinase (JNK) signaling pathway with phosphorylated JNK (p-JNK), phosphorylated insulin receptor substrate (p-IRS), serine/threonine protein kinase (Akt), phosphorylated Akt (p-Akt), and phosphorylated tau (p-tau). Finally, rutin, orientin, isoorientin, and luteolin-7-O-rutinoside as the main phenolics of EFDM were identified using ultra-performance liquid chromatography/quadrupole time of flight tandem mass spectrometry (UPLC-QTOF/MS(2)). These findings suggest that EFDM may have an effect as a multiple preventive substances to reduce diabetes-associated cognitive dysfunction.

Antiamnesic Effect of Broccoli (Brassica oleracea var. italica) Leaves on Amyloid Beta (Aß)1-42-Induced Learning and Memory Impairment.

To examine the antiamnesic effects of broccoli (Brassica oleracea var. italica) leaves, we performed in vitro and in vivo tests on amyloid beta (Aß)-induced neurotoxicity. The chloroform fraction from broccoli leaves (CBL) showed a remarkable neuronal cell-protective effect and an inhibition against acetylcholinesterase (AChE). The ameliorating effect of CBL on Aß1-42-induced learning and memory impairment was evaluated by Y-maze, passive avoidance, and Morris water maze tests. The results indicated improving cognitive function in the CBL group. After the behavioral tests, antioxidant effects were detected by superoxide dismutase (SOD), oxidized glutathione (GSH)/total GSH, and malondialdehyde (MDA) assays, and inhibition against AChE was also presented in the brain. Finally, oxo-dihydroxy-octadecenoic acid (oxo-DHODE) and trihydroxy-octadecenoic acid (THODE) as main compounds were identified by quadrupole time-of-flight ultraperformance liquid chromatography (Q-TOF UPLC-MS) analysis. Therefore, our studies suggest that CBL could be used as a natural resource for ameliorating Aß1-42-induced learning and memory impairment.

Reversal of Trimethyltin-Induced Learning and Memory Deficits by 3,5-Dicaffeoylquinic Acid.

The antiamnesic effect of 3,5-dicaffeoylquinic acid (3,5-diCQA) as the main phenolic compound in Artemisia argyi H. extract on cognitive dysfunction induced by trimethyltin (TMT) (7.1 µg/kg of body weight; intraperitoneal injection) was investigated in order to assess its ameliorating function in mice. In several behavioral tests, namely, the Y-maze, passive avoidance, and Morris water maze (MWM) test, 3,5-diCQA significantly ameliorated learning and memory deficits. After the behavioral tests, brain tissues from the mice were analyzed to characterize the basis of the neuroprotective effect. Acetylcholine (ACh) levels increased, whereas the activity of acetylcholinesterase (AChE) decreased upon administration of 3,5-diCQA. In addition, 3,5-diCQA effectively protected against an increase in malondialdehyde (MDA) content, an increase in the oxidized glutathione (GSH) ratio, and a decline of total superoxide dismutase (SOD) level. 3,5-diCQA may prevent neuronal apoptosis through the protection of mitochondrial activities and the repression of apoptotic signaling molecules such as p-Akt, BAX, and p-tau (Ser 404).