Jong-Heum Park

The procyanidin trimer C1 inhibits LPS-induced MAPK and NF-κB signaling through TLR4 in macrophages

Natural products and dietary components rich in polyphenols have been shown to reduce inflammation; however, the molecular mechanisms underlying this anti-inflammatory activity are not completely characterized, and many features remain to be elucidated. This research was carried out to clarify the potential role of procyanidin trimer C1 in the anti-inflammatory effect of polyphenols. Procyanidin C1 inhibited inducible nitric oxide synthase-mediated nitric oxide production and the release of pro-inflammatory cytokines (interleukin-6 and tumor necrosis factor-α) in lipopolysaccharide (LPS)-induced macrophages. Treatment with procyanidin C1 resulted in a significant decrease in prostaglandin E2 and cyclooxygenase-2 levels, as well as the expression of cell surface molecules (CD80, CD86, and MHC class II), which was induced by LPS. Furthermore, our data demonstrated that the anti-inflammatory effect of procyanidin C1 occurs through inhibition of mitogen-activated protein kinase (p38 and c-Jun N-terminal kinase) and nuclear factor-κB signaling pathways. These 2 factors play a major role in controlling inflammation, through toll-like receptor 4, suggesting that procyanidin C1 plays a potent role in promoting anti-inflammatory activity in macrophages. These results represent a novel and effective therapeutic intervention for the treatment of inflammatory disease.

Effect of gamma irradiation on mistletoe (Viscum album) lectin-mediated toxicity and immunomodulatory activity

This study evaluated the effect of gamma irradiation on the reduction of the toxicity of mistletoe lectin using both in vitro and in vivo models. To extract the lectin from mistletoe, an (NH4)2SO4 precipitation method was employed and the precipitant purified using a Sepharose 4B column to obtain the pure lectin fraction. Purified lectin was then gamma‐irradiated at doses of 0, 5, 10, 15, and 20 kGy, or heated at 100 °C for 30 min. Toxic effects of non‐irradiated, irradiated, and heat‐treated lectins were tested using hemagglutination assays, cytotoxicity assays, hepatotoxicity, and a mouse survival test and immunological response was tested using cytokine production activity. Hemagglutination of lectin was remarkably decreased (P < 0.05) by irradiation at doses exceeding 10 kGy and with heat treatment. However, lectin irradiated with 5 kGy maintained its hemagglutination activity. The cytotoxicity of lectin was decreased by irradiation at doses over 5 kGy and with heat treatment. In experiments using mouse model, glutamate oxaloacetate transaminase (GOT) and glutamic pyruvic transaminase (GPT) levels were decreased in the group treated with the 5 kGy irradiated and heat‐treated lectins as compared to the intact lectin, and it was also shown that 5 kGy irradiated and heat‐treated lectins did not cause damage in liver tissue or mortality. In the result of immunological response, tumor necrosis factor (TNF‐α) and interleukin (IL‐6) levels were significantly (P < 0.05) increased in the 5 kGy gamma‐irradiated lectin treated group. These results indicate that 5 kGy irradiated lectin still maintained the immunological response with reduction of toxicity. Therefore, gamma‐irradiation may be an effective method for reducing the toxicity of lectin maintaining the immune response.

The supplementation of Korean mistletoe water extracts reduces hot flushes, dyslipidemia, hepatic steatosis, and muscle loss in ovariectomized rats

Since Korean mistletoe (Viscum album) has been used for alleviating metabolic diseases, it may also prevent the impairment of energy, glucose, lipid, and bone metabolisms in an estrogen-deficient animal model. We determined that long-term consumption of Korean mistletoe water extract (KME) can alleviate menopausal symptoms such as hot flush, increased abdominal fat mass, dyslipidemia, hyperglycemia, and decreased bone mineral density in ovariectomized (OVX) rats fed a high-fat diet, and explored the mechanisms of the effects. OVX rats were divided into four groups and fed high-fat diets supplemented with either 0.6% dextrin (control), 0.2% lyophilized KME + 0.4% dextrin (KME-L), or 0.6% lyophilized KME (KME-H). Sham rats were fed with the high-fat diets with 0.6% dextrin as a normal-control without estrogen deficiency. After eight weeks, OVX rats exhibited impaired energy, glucose and lipid metabolism, and decreased uterine and bone masses. KME-L did not alleviate energy dysfunction. However, KME-H lowered serum levels of total-, LDL-cholesterol, and triglycerides and elevated serum HDL-cholesterol levels in OVX rats with dyslipidemia, to similar levels as normal-control rats. Furthermore, KME-H improved HOMA-IR, an indicator of insulin resistance, in OVX rats. Surprisingly, KME-H fed rats had greater lean mass in the abdomen and leg without differences in fat mass but neither dosage of KME altered bone mineral density in the lumbar spine and femur. The increased lean mass was related to greater phosphorylation of mTOR and eukaryotic translation initiation factor 4E-binding protein 1 (4E-BP1) in the quadriceps muscles. Hepatic triglyceride contents were lowered with KME-H in OVX rats by increasing carnitine palmitoyltransferase-1 (CPT-1) expression and decreasing fatty acid synthase (FAS) and sterol regulatory element-binding protein-1c (SREBP-1c) expression. In conclusion, KME may be useful for preventing some menopausal symptoms such as hot flushes, dyslipidemia, hepatic steatosis, and loss of muscle mass in post-menopausal women.

Rutin attenuates ethanol-induced neurotoxicity in hippocampal neuronal cells by increasing aldehyde dehydrogenase 2.

Rutin is derived from buckwheat, apples, and black tea. It has been shown to have beneficial anti-inflammatory and antioxidant effects. Ethanol is a central nervous system depressant and neurotoxin. Its metabolite, acetaldehyde, is critically toxic. Aldehyde dehydrogenase 2 (ALDH2) metabolizes acetaldehyde into nontoxic acetate. This study examined rutins effects on ALDH2 activity in hippocampal neuronal cells (HT22 cells). Rutins protective effects against acetaldehyde-based ethanol neurotoxicity were confirmed. Daidzin, an ALDH2 inhibitor, was used to clarify the mechanisms of rutins protective effects. Cell viability was significantly increased after rutin treatment. Rutin significantly reversed ethanol-increased Bax, cytochrome c expression and caspase 3 activity, and decreased Bcl-2 and Bcl-xL protein expression in HT22 cells. Interestingly, rutin increased ALDH2 expression, while daidzin reversed this beneficial effect. Thus, this study demonstrates rutin protects HT22 cells against ethanol-induced neurotoxicity by increasing ALDH2 activity.

Procyanidin C1 Causes Vasorelaxation Through Activation of the Endothelial NO/cGMP Pathway in Thoracic Aortic Rings

The aim of this study was to clarify the efficacy of procyanidin C1 (Pro C1) for modulating vascular tone. Pro C1 induced a potent vasorelaxant effect on phenylephrine-constricted endothelium-intact thoracic aortic rings, but had no effect on denuded thoracic aortic rings. Moreover, Pro C1 caused a significant increase in nitric oxide (NO) production in endothelial cells. Pro C1-induced vasorelaxation and Pro C1-induced NO production were significantly decreased in the presence of a nonspecific potassium channel blocker (tetraethylammonium chloride [TEA]), an endothelial NO synthase inhibitor (N(G)-monomethyl-L-arginine [L-NMMA]), and a store-operated calcium entry inhibitor (2-aminoethyl diphenylborinate [2-APB]). Pro C1-induced vasorelaxation was also completely abolished by an inhibitor of soluble guanyl cyclase, which suggests that the Pro C1 effects observed involved cyclic guanosine monophosphate (cGMP) production. Interestingly, Pro C1 significantly enhanced basal cGMP levels. Taken together, these results indicate that Pro C1-induced vasorelaxation is associated with the activation of the calcium-dependent NO/cGMP pathway, involving potassium channel activation. Thus, Pro C1 may represent a novel and potentially therapeutically relevant compound for the treatment of cardiovascular diseases.

Viscothionin Isolated from Korean Mistletoe Improves Nonalcoholic Fatty Liver Disease via the Activation of Adenosine Monophosphate-Activated Protein Kinase

The present study investigated the effects of viscothionin, a compound isolated from Korean mistletoe (Viscum album coloratum), on nonalcoholic fatty liver disease (NAFLD) in both in vitro and in vivo models. A connection was discovered between viscothionin and the adenosine monophosphate-activated protein kinase (AMPK) signaling pathway, which is involved in lipid metabolism. Viscothionin was shown to significantly attenuate lipid accumulation in HepG2 cells treated with oleic acid, which induces lipid accumulation. Moreover, the phosphorylation of AMPK and acetyl-coenzyme A carboxylase in HepG2 cells was increased by viscothionin treatment. Viscothionin was orally administered to high fat diet-induced obese mice and subsequently histopathological analysis associated with AMPK signaling pathways was evaluated. A significant reduction in the extent of hepatic steatosis was revealed in viscothionin-treated obese mice. Thus, viscothionin mediates its beneficial effects on NAFLD via AMPK signaling pathways, suggesting that it may be a potential target for novel NAFLD treatments.

Identification of red pepper powder irradiated with different types of radiation using luminescence methods: A comparative study

The purpose of this study was to verify the reliability of photostimulated luminescence (PSL) and thermoluminescence (TL) methods for identifying irradiated foods, described in the European standards EN 13751:2002 and EN 1788:2001, respectively, which were established solely through interlaboratory studies on gamma-irradiated food. Red pepper powder samples irradiated with electron-beams (e-beams), gamma rays and high-energy X-rays were used as model foods. Samples irradiated with each radiation type at ⩾4 kGy could be correctly identified by the PSL method, whereas samples irradiated at ⩾0.5 kGy with each radiation type could be correctly recognized by the TL method when e-beams, gamma rays, or high-energy X-rays were used as normalization sources. However, different TL intensities were observed for minerals separated from red pepper powder for different irradiation sources, which was confirmed using pure quartz and K-feldspar minerals. Further interlaboratory studies are required to verify this phenomenon.

Comparison of the isolation rates and characteristics of Salmonella isolated from antibiotic-free and conventional chicken meat samples

&NA; Salmonella contamination in chicken samples can cause major health problems in humans. However, not only the effects of antibiotic treatment during growth but also the impacts of the poultry slaughter line on the prevalence of Salmonellae in final chicken meat sold to consumers are unknown. In this study, we compared the isolation rates and antimicrobial resistance of Salmonellae among antibiotic‐free, conventional, conventional Korean native retail chicken meat samples, and clonal divergence of Salmonella isolates by multilocus sequence typing. In addition, the distribution of extended‐spectrum &bgr;‐lactamase (ESBL) genes in ESBL‐producing Salmonella isolates was analyzed. A total of 72 retail chicken meat samples (n = 24 antibiotic‐free broiler [AFB] chickens, n = 24 conventional broiler [CB] chickens, and n = 24 conventional Korean native [CK] chickens) was collected from local retail markets in Seoul, South Korea. The isolation rates of Salmonellae were 66.6% in AFB chickens, 45.8% in CB chickens, and 25% in CK chickens. By analyzing the minimum inhibitory concentrations of &bgr;‐lactam antibiotics with the disc‐diffusion test, we found that 81.2% of Salmonella isolates from AFB chickens, 63.6% of isolates from CB chickens, and 50% of isolates from CK chickens were ESBL producers; all ESBL‐positive isolates had the CTX‐M‐15 genotype. Interestingly, all ESBL‐producing Salmonellae were revealed as ST16 by multilocus sequence typing and had the genetic platform of blaCTX‐M gene (IS26‐ISEcp1‐blaCTX‐M‐15‐IS903), which was first reported in Salmonellae around the world. The Salmonella ST33 strain (S. Hadar) isolated in this study has never been reported in South Korea. In conclusion, our findings showed that antibiotic‐free retail chicken meat products were also largely contaminated with ESBL‐producing Salmonellae and that their ESBL genes and genetic platforms were the same as those isolated from conventional retail chicken meat products.

Low molecular weight β-glucan stimulates doxorubicin-induced suppression of immune functions in mice

The aim of this study was to evaluate the protective effect of low molecular weight β-glucan (LMG) against doxorubicin (DOX)-induced immune suppression of tumor-bearing mice. The tumor size and spleen cell functions such as spleen cell proliferation, cytokine production (interferon-γ and interleukin-2), and the population of CD4+ and CD8+ T cells were estimated. In the tumorbearing mice, the tumor size was significantly (p<0.05) decreased by DOX treatment. However, there was no significant difference between mice treated with high molecular weight β-glucan (HMG) and mice treated with LMG. Spleen cell proliferation and cytokine production were significantly (p<0.05) decreased in only DOX treated group, but increased in all β-glucan treated groups with DOX. Moreover, the populations of CD4+ and CD8+ T cells were also increased in the LMG-treated group. It appears that LMG effectively reduces the DOX-induced immune toxicity through activation of immune cells such as splenocytes.

Toxicological evaluation of 2-dodecylcyclobutanone, a unique radiolytic compound of palmitic acid

This study was conducted to evaluate the toxic effects and potency of 2-dodecylcyclobutanone (2-dDCB), a unique compound derived from palmitic acid via irradiation. In a series of assays of bacterial reverse-mutation, in vitro chromosomal aberration, and in vivo micronucleus, negative responses were found by the treatment of 2-dDCB comparing vehicle control, dimethyl sulfoxide or corn oil. In the acute oral toxicity test, all of the mice administrated 2-dDCB survived, and there were no clinical and necropsy signs observed at any doses (0, 300, and 2000 mg/kg body weight) during the experimental period of 14 days. These results suggested that 2-dDCB is a relatively non-toxic substance with median lethality dose higher than 2000 mg/kg body weight. Moreover, there were no adverse effects noted in rats orally administrated 2-dDCB everyday via gavage for 28 days, even at the highest dose (2.0 mg/kg body weight/day) tested, which is 1000-times higher than the human daily intake of 2-dDCB estimated through an extreme exposure scenario. Overall, these results indicate that 2-dDCB is not likely to raise any human health concerns and irradiated foods containing palmitic acid can be recognized as safe for human consumption under the current international regulation systems for food irradiation.