Ho Jin Heo

Naringenin from Citrus junos has an inhibitory effect on acetylcholinesterase and a mitigating effect on amnesia.

This study was performed to identify safe and more effective acetylcholinesterase (AChE) inhibitors in the treatment of Alzheimer’s disease. The total methanol extract of Citrus junos had a significant inhibitory effect on AChE in vitro. By sequential fractionation of C. junos, the active component was finally identified as naringenin. Naringenin inhibited AChE activity in a dose-dependent manner. In this study, we also evaluated the anti-amnesic activity of naringenin, a major flavanone constituent isolated from C. junos, in vivo using ICR mice with amnesia induced by scopolamine (1 mg/kg body weight). Naringenin, when administered to mice at 4.5 mg/kg body weight, significantly ameliorated scopolamine-induced amnesia as measured in both the passive avoidance and the Y-maze test. These results suggest that naringenin may be a useful chemopreventive agent against Alzheimer’s disease.

Neuroprotective and anti-oxidant effects of caffeic acid isolated from Erigeron annuus leaf

BackgroundSince oxidative stress has been implicated in a neurodegenerative disease such as Alzheimers disease (AD), natural antioxidants are promising candidates of chemopreventive agents. This study examines antioxidant and neuronal cell protective effects of various fractions of the methanolic extract of Erigeron annuus leaf and identifies active compounds of the extract.MethodsAntioxidant activities of the fractions from Erigeron annuus leaf were examined with [2,2-azino-bis(3-ethylbenz thiazoline-6-sulfonic acid diammonium salt)] (ABTS) and ferric reducing antioxidant power (FRAP) assays. Neuroprotective effect of caffeic acid under oxidative stress induced by H2O2 was investigated with [3-(4,5-dimethythiazol-2-yl)-2,5-diphenyl tetrazolium bromide] (MTT) and lactate dehydrogenase (LDH) assays.ResultsThis study demonstrated that butanol fraction had the highest antioxidant activity among all solvent fractions from methanolic extract E. annuus leaf. Butanol fraction had the highest total phenolic contents (396.49 mg of GAE/g). Caffeic acid, an isolated active compound from butanol fraction, showed dose-dependent in vitro antioxidant activity. Moreover, neuronal cell protection against oxidative stress induced cytotoxicity was also demonstrated.ConclusionErigeron annuus leaf extracts containing caffeic acid as an active compound have antioxidative and neuroprotective effects on neuronal cells.

Ferulic Acid Supplementation Prevents Trimethyltin-Induced Cognitive Deficits in Mice

This study’s objective was to clarify the ameliorative effects ferulic acid (4-hydroxy-3-methoxycinnamic acid) has against cognitive deficits and ChAT activation in trimethyltin (TMT) induced, memory injured mice following a 28-d ferulic acid treatment. After administering TMT for 3 d, each mouse performed Y-maze and passive avoidance tests to check immediate working memory performance and cognitive function. The results showed that ferulic acid administration attenuated TMT-induced memory injury and a decline in ChAT activity in the mice. This suggests that ferulic acid might be useful for preventing cognitive dysfunction as well as for boosting the activation of ChAT in dementia.

Ameliorative effect of 1,2-benzenedicarboxylic acid dinonyl ester against amyloid beta peptide-induced neurotoxicity.

Amyloid beta peptide (Aβ)-induced oxidative stress may be linked to neurodegenerative disease. Ethanol extracts of Rosa laevigata protected PC12 cells from hydrogen peroxide-induced oxidative stress. (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) reduction assays revealed a significant increase in cell viability when oxidatively stressed PC12 cells were treated with R. laevigata extract. The effect of R. laevigata on oxidative stress-induced cell death was further investigated by lactate dehydrogenase release assays and trypan blue exclusion assays. Administration of 1,2-benzenedicarboxylic acid dinonyl ester from R. laevigata extract to mice infused with Aβ significantly reversed learning and memory impairment in behavioural tests. After behavioural testing, the mice were sacrificed and brains were collected for the examination of lipid peroxidation, catalase activity and acetylcholinesterase (AchE) activity. These results suggest that 1,2-benzenedicarboxylic acid dinonyl ester from R. laevigata extract may be able to reduce Aβ-induced neurotoxicity, possibly by reducing oxidative stress. Therefore, R. laevigata extract may be useful for the prevention of oxidative stress-induced neurodegenerative disorders.

Protective effect of Rosa laevigata against amyloid beta peptide-induced oxidative stress.

The amyloid beta (Aβ) peptide is known to increase free radical production in nerve cells, leading to cell death. To investigate the effect of Rosa laevigata against Aβ-induced oxidative damage, in vitro assays and in vivo behavioral tests were performed. R. laevigata showed cell protective effects against oxidative stress-induced cytotoxicity. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) reduction assay exhibited significant increase in cell viability when rat pheochromocytoma (PC 12) cells were treated with R. laevigata extracts. Administration of R. laevigata extracts to mice significantly reversed the Aβ-induced learning and memory impairment in in vivo behavioral tests. These results suggest that R. laevigata extracts can reduce the cytotoxicity of Aβ in PC 12 cells, possibly by the reduction of oxidative stress, and these extracts may be useful in the prevention of Alzheimers disease.

Punica granatum Protects Against Oxidative Stress in PC12 Cells and Oxidative Stress-Induced Alzheimer's Symptoms in Mice

Alzheimers disease (AD) is a progressive degenerative brain disorder that is characterized by neuronal loss, neurofibrillary tangles, and the abnormal deposition of senile plaque and amyloid β peptide (Aβ). The brains of AD patients are under intense oxidative stress. The overproduction of Aβ leads to Aβ-associated free radical oxidative stress. In this study, the antioxidative and neuronal protective effects of Punica granatum extract were investigated against oxidative stress-induced cytotoxicity in PC12 cells. The ethanol extracts of P. granatum protected PC12 cells from hydrogen peroxide (H₂O₂-induced oxidative stress. 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assays revealed a significant increase in cell viability when oxidatively stressed PC12 cells were treated with the P. granatum extract. To examine the effects of P. granatum on Aβ₁₋₄₂-induced learning and memory impairment in mice, in vivo behavioral tests were performed. Treatment with the extract of P. granatum increased step-through latency in mice injected with Aβ₁₋₄₂. The results of this study suggest that the ethanol extract of P. granatum mitigated H₂O₂-induced oxidative stress in PC12 cells. In addition, the extract inhibited neuronal cell death caused by Aβ-induced oxidative stress and Aβ-induced learning and memory deficiency.

Anthocyanins in the ripe fruits of Rubus coreanus Miquel and their protective effect on neuronal PC-12 cells

Phenolics of the fresh ripe fruits of Rubus coreanus Miquel were extracted and separated into anthocyanin and the non-anthocyanin fractions, which were used for the evaluation for antioxidant capacity and neuroprotective effects. The anthocyanin fraction accounted for approximately 47-55% of the total antioxidant capacity of the whole extract and had significantly higher free radical-scavenging capacity than the non-anthocyanin fraction. Furthermore, the anthocyanins alleviated intracellular oxidative stress, as assayed by in vitro fluorescent measurements. The anthocyanins showed neuroprotective effects on PC-12 cells in vitro against oxidative stress in a dose-dependent manner. Triple quadrupole LC/MS and Q-TOF LC/MS analyses revealed four major anthocyanins; cyanidin 3-O-sambubioside, cyanidin 3-O-glucoside, cyanidin 3-O-xylosylrutinoside, and cyanidin 3-O-rutinoside in increasing order of amounts. These results demonstrated that anthocyanins are the major components and contributors to the antioxidant capacity of ripe R. coreanus Miquel fruits. Further studies are warranted to determine whether consumption of the fruits reduces oxidative stress in the brain and promotes health.

Antineurodegenerative Effect of Phenolic Extracts and Caffeic Acid Derivatives in Romaine Lettuce on Neuron-Like PC-12 Cells

In recent decades, romaine lettuce has been one of the fastest growing vegetables with respect to its consumption and production. An understanding is needed of the effect of major phenolic phytochemicals from romaine lettuce on biological protection for neuron-like PC-12 cells. Phenolics in fresh romaine lettuce were extracted, and then its total phenolics and total antioxidant capacity were measured spectrophotometrically. Neuroprotective effects of phenolic extract of romaine lettuce and its pure caffeic acid derivatives (caffeic, chicoric, chlorogenic, and isochlorogenic acids) in PC-12 cells were evaluated using two different in vitro methods: lactate dehydrogenase release and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide reduction assays. Total phenolics and total antioxidant capacity of 100 g of fresh romaine lettuce averaged 22.7 mg of gallic acid equivalents and 31.0 mg of vitamin C equivalents, respectively. The phenolic extract of romaine lettuce protected PC-12 cells against oxidative stress caused by H(2)O(2) in a dose-dependent manner. Isochlorogenic acid, one of the phenolics in romaine lettuce, showed stronger neuroprotection than the other three caffeic acid derivatives also found in the lettuce. Although romaine lettuce had lower levels of phenolics and antioxidant capacity compared to other common vegetables, its contribution to total antioxidant capacity and antineurodegenerative effect in human diets would be higher because of higher amounts of its daily per capita consumption compared to other common vegetables.

Daidzein Activates Choline Acetyltransferase from MC-IXC Cells and Improves Drug-Induced Amnesia

The choline acetyltransferase (ChAT) activator, which enhances cholinergic transmission via an augmentation of the enzymatic production of acetylcholine (ACh), is an important factor in the treatment of Alzheimer’s disease (AD). Methanolic extracts from Pueraria thunbergiana exhibited an activation effect (46%) on ChAT in vitro. Via the sequential isolation of Pueraria thunbergiana, the active component was ultimately identified as daidzein (4′,7-dihydroxy-isoflavone). In order to investigate the effects of daidzein from Pueraria thunbergiana on scopolamine-induced impairments of learning and memory, we conducted a series of in vivo tests. Administration of daidzein (4.5 mg/kg body weight) to mice was shown significantly to reverse scopolamine-induced amnesia, according to the results of a Y-maze test. Injections of scopolamine into mice resulted in impaired performance on Y-maze tests (a 37% decreases in alternation behavior). By way of contrast, mice treated with daidzein prior to the scopolamine injections were noticeably protected from this performance impairment (an approximately 12%–21% decrease in alternation behavior). These results indicate that daidzein might play a role in acetylcholine biosynthesis as a ChAT activator, and that it also ameliorates scopolamine-induced amnesia.

Zeatin Prevents Amyloid β-Induced Neurotoxicity and Scopolamine-Induced Cognitive Deficits

The antioxidative and protective effects of zeatin against amyloid beta-protein (Abeta)-induced neurotoxicity were investigated using PC12 cells. Zeatin showed antioxidative and cell protective effects against Abeta-induced neurotoxicity. In this study, we also evaluated the effect of zeatin on learning and memory capacity in vivo using ICR mice with amnesia induced by scopolamine (1 mg/kg of body weight). Zeatin, when administered to mice at 4.5 mg/kg of body weight, significantly ameliorated scopolamine-induced amnesia as measured in both the passive avoidance test and Y-maze test. Injecting mice with scopolamine impaired performance on the passive avoidance test (48 +/- 4.5% decrease) and on the Y-maze test (12 +/- 1.3% decrease). In contrast, mice treated with zeatin before scopolamine injections were protected from these changes (5-34% decrease in step-through latency; 1-4% decrease in alternation behavior). The present results suggest a possible chemopreventive role of zeatin in Alzheimers disease.