Hong-Yon Cho

Role of the Conjugated Linoleic Acid in the Prevention of Cancer

There are multiple lines of evidence that a variety of natural fatty acids are effective in health promotion. Among these fatty acids, conjugated linoleic acid (CLA)—a collective term referring to a mixture of positional and geometric isomers of linoleic acid (LA, cis-9, cis-12-octadecadienoic acid)—is currently under intensive investigation due to its health-promotion potential. The antitumor activity of CLA is of special interest, since it shows inhibitory effects against multistage carcinogenesis at relatively low dietary levels. Many studies using in vivo and in vitro models have shown that CLA suppresses the development of multistage carcinogenesis at different sites. The research to date on CLA has provided a vast amount of information about the mechanism on how CLA functions in the prevention of cancer. This article discusses characteristics of CLA in the prevention of cancer in both in vivo and in vitro studies and the possible underlying chemoprevention mechanisms.

In vitro and in vivo hepatoprotective effects of the aqueous extract from Taraxacum officinale (dandelion) root against alcohol-induced oxidative stress

The protective effects of Taraxacum officinale (dandelion) root against alcoholic liver damage were investigated in HepG2/2E1 cells and ICR mice. When an increase in the production of reactive oxygen species was induced by 300 mM ethanol in vitro, cell viability was drastically decreased by 39%. However, in the presence of hot water extract (TOH) from T. officinale root, no hepatocytic damage was observed in the cells treated with ethanol, while ethanol-extract (TOE) did not show potent hepatoprotective activity. Mice, which received TOH (1 g/kg bw/day) with ethanol revealed complete prevention of alcohol-induced hepatotoxicity as evidenced by the significant reductions of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase activities compared to ethanol-alone administered mice. When compared to the ethanol-alone treated group, the mice receiving ethanol plus TOH exhibited significant increases in hepatic antioxidant activities, including catalase, glutathione-S-transferase, glutathione peroxidase, glutathione reductase, and glutathione. Furthermore, the amelioration of malondialdehyde levels indicated TOHs protective effects against liver damage mediated by alcohol in vivo. These results suggest that the aqueous extract of T. officinale root has protective action against alcohol-induced toxicity in the liver by elevating antioxidative potentials and decreasing lipid peroxidation.

Angiotensin I-converting enzyme inhibitor from Grifola frondosa

To investigate the hypotensive compounds from edible mushroom, extracts from 10 fruit bodies of mushrooms were screened for the inhibitory activity against angiotensin I converting enzyme (ACE). The most potent ACE inhibitory activity (58.7%) was detected in a cold water extract of Grifola frondosa, with an IC50 of 0.95 mg. The ACE inhibitory activities of the cold and hot water extracts increased as the extraction time increased, but decreased slightly 15 h and 90 min, respectively, after extraction. After the purification of ACE inhibitory peptides with acetone fractionation and column chromatography, we obtained an active fraction with an IC50 of 0.13 mg and a yield of 0.7%. The purified inhibitor showed competitive inhibition on ACE and this peptide maintained inhibitory activity even after digestion by intestinal proteases.

Antioxidant effects of Origanum majorana L. on superoxide anion radicals

A purified compound with antioxidant properties (28 mg), T3b, was isolated from a methanol extract (10 g) of Origanum majorana L. by sequential procedures, with silica gel column, thin-layer, and LH-20 Sephadex gel column chromatographies. The in vitro scavenging activity of T3b on superoxide anion radical (O2−) was investigated and compared to those of seven commercially available synthetic or natural antioxidants. Of those, the strongest scavenging action was observed in T3b with an IC50 of 1.44 μg/ml. The T3b also exhibited significant inhibitory effects on 12-O-tetradecanolyphorbol-13-acetate (TPA)-induced O2− generation and hydrogen peroxide formation in differentiated HL-60 cells, indicating that the isolated compound is a potent chemopreventer. The purified compound from O. majorana L. was shown to possess both O2− scavenging activity and an inhibitory effect against TPA-induced O2− generation.

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.

Effects of Oleamide on Choline Acetyltransferase and Cognitive Activities

We screened 50 Korean traditional natural plants to measure the activation effect on choline acetyltransferase and attenuation of scopolamine-induced amnesia. The methanolic extracts from Zizyphus jujuba among the tested 50 plants, showed the highest activatory effect (34.1%) on choline acetyltransferase in vitro. By sequential fractionation of Zizyphus jujuba, the active component was finally identified as cis-9-octadecenoamide (oleamide). After isolation, oleamide showed a 65% activation effect. Administration of oleamide (0.32%) to mice significantly reversed the scopolamine-induced memory and/or cognitive impairment in the passive avoidance test and Y-maze test. Injection of scopolamine to mice impaired performance on the passive avoidance test (31% decrease in step-through latency), and on the Y-maze test (16% decrease in alternation behavior). In contrast, mice treated with oleamide before scopolamine injection were protected from these changes (12–25% decrease in step-through latency; 1–10% decrease in alternation behavior). These results suggest that oleamide should be a useful chemo-preventive agent against Alzheimers disease.

Neurotoxic Effects of Alcohol and Acetaldehyde During Embryonic Development

Alcohol drinking during pregnancy results in abnormal fetal development, including fetal alcohol syndrome (FAS) in humans and experimental animals. FAS is characterized by two major effects, including central nervous system (CNS) dysfunction and multiple anomalies recognizable mainly as a typical face. However, the mechanisms of alcohol-induced embryotoxicity have not been clearly demonstrated. The aim of the present study was to investigate the possible mechanisms underlying ethanol-induced FAS in the developing embryo. First, ethanol-induced developmental abnormalities were investigated in vitro. Postimplantation embryos at gestation day (GD) 9.5 were cultured for 48 h and observed for morphological changes. Ethanol-mediated changes in proteins regulated apoptosis (p53 and bcl-2), antioxidant (vitamin E and catalase) activities, generation of reactive oxygen species (ROS), and oxidative DNA damage shown as 8-hydroxy-2′-deoxyguanosine (8-OHdG) were measured in embryonic midbrain cells. Alcohol or acetaldehyde significantly induced cytotoxicity in cultured rat embryonic midbrain cells. The levels of p53, bcl-2, and 8-OHdG were concomitantly changed by alcohol and acetaldehyde treatment in midbrain cells. Injured cells induced by ROS were increased by alcohol or acetaldehyde treatment in midbrain cells. Cotreatment with alcohol or acetaldehyde and catalase decreased cytotoxicity in midbrain cells. In postimplantation embryo culture, alcohol or acetaldehyde-treated embryos showed retardation of embryonic growth and development in a concentration-dependent manner. These results indicate that alcohol and its metabolite acetaldehyde induce fetal developmental abnormalities by disrupting cellular differentiation and growth. Data demonstrate that some antioxidants can partially protect against the alcohol-induced embryonic developmental toxicity.

Protective Effects of Kaempferol (3,4',5,7-tetrahydroxyflavone) against Amyloid Beta Peptide (Aβ)-Induced Neurotoxicity in ICR Mice

To determine the effects of kaempferol, rat pheochromocytoma cells (PC12) and Institute of Cancer Research (ICR) mice were utilized as neuronal models. Using in vitro assays, kaempferol was shown to have protective effects against oxidative stress-induced cytotoxicity in PC12 cells. Administration of kaempferol also significantly reversed amyloid beta peptide (Aβ)-induced impaired performance in a Y-maze test. Taken altogether, the results reported here suggest that further investigation is warranted of the influence of kaempferol on pathways related to Alzheimer’s disease.

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.

Inhibitory effect of Poncirus trifoliate on acetylcholinesterase and attenuating activity against trimethyltin-induced learning and memory impairment.

Various native Korean plants were screened to find an effective acetylcholinesterase (AChE) inhibitor for the treatment of Alzheimer’s disease (AD). Among these plants, the ethanol extract of Poncirus trifoliate was selected for isolating the AChE inhibitor because it exhibited the highest inhibitory activity (47.31%). To separate the active compound from Poncirus trifoliate, solvent partition, open column chromatography, thin-layer chromatography (TLC), and high-performance liquid chromatography (HPLC) were utilized. The putative chemical structure of the AChE inhibitor was identified as methoxsalen by successive analysis with electron ionization mass spectrometry (EI-MS) and 13C/1H-nuclear magnetic resonance (NMR). To confirm the attenuating effect of the Poncirus trifoliate extract against trimethyltin (TMT)-induced neurotoxicity, in vivo behavior tests were carried out. Our findings suggest that the Poncirus trifoliate extract significantly reversed TMT-induced learning and memory impairment. These results demonstrate that the Poncirus trifoliate extract could possess a wide range of beneficial activities for neurodegenerative disorders, notably AD.