• Journal of Life Science
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• v.28 no.11
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• pp.1369-1378
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• 2018

Prunus mume Siebold & Zucc., a member of the Rosaceae family (called Maesil in Korea), has been widely distributed in East Asia, e.g. Korea, Japan and China, and its fruit has been used as a traditional drug and health food. In this study, we evaluated physicochemical properties and physiological activities of condensed Prunus mume juice treated with pectinase (PJ). The values of total acidity, pH, sugar contents, turbidity moisture content of the PJ were 35.81%, 2.73, $54.36^{\circ}Brix$, 2.75 and 51.32%, respectively. The PJ had effective DPPH radical scavenging activity, reducing power effect, $H_2O_2$ scavenging activity and ${\beta}$-carotene bleaching effect. DPPH radical scavenging activities of PJ was 46.31%; their reducing power ($OD_{700}$) was 1.80; $H_2O_2$ scavenging activity of PJ was 91.62%; and ${\beta}$-carotene bleaching effect of PJ was 73.02%. Also, PJ showed effective levels of ${\alpha}$-glucosidase inhibition activity. The cell viability was measured by SRB assay. The PJ significantly decreased the cell viability of mouse melanoma cells (B16) and human melanoma cells (SK-MEL-2 and SK-MEL-28) in a dose-dependent manner, however, there was no effect on human keratinocyte HaCaT. In morphological study, PJ-treated SK-MEL-2 cells showed distorted and shrunken cell masses. Total polyphenol contents and total flavonoid contents of PJ were 588.31 mg% (gallic acid equivalent) and 860.45 mg% (rutin equivalent). The antiproliferative effect of PJ seems to be associated with the antioxidant activity of its flavonoid and polyphenol contents. In conclusion, PJ may be beneficial in development of a functional food material.

• Journal of Life Science
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• v.29 no.4
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• pp.484-491
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• 2019

Proanthocyanidins are naturally occurring polyphenolic compounds abundant in many vegetables, plant skins (rind/bark), seeds, flowers, fruits, and nuts. Numerous in vitro and in vivo studies have demonstrated myriad effects potentially beneficial to human health, such as antioxidation, immunomodulation, DNA repair, and antitumor activity. Among immune cells, macrophages are crucial players in a variety of inflammatory responses to environmental conditions. However, it has been widely reported that macrophages cause chronic inflammation and are involved in a variety of diseases, such as obesity, diabetes, metabolic syndrome, and cancer. In this study, we report the suppressive effect of proanthocyanidins via the heme oxygenase-1 (HO-1)-related system, on the immune response of the LPS-stimulated mouse macrophage cell line RAW264.7. Increased HO-1 expression at mRNA and protein levels were found in proanthocyanidins-treated RAW264.7 cells. Further, proanthocyanidins enhanced nuclear factor-erythroid 2-related factor 2 translocation into the nucleus. RAW264.7 cells were treated with lipopolysaccharide (LPS) with or without proanthocyanidins, and inflammatory mediator expression levels were assessed. Proanthocyanidins treatment resulted in the attenuation of nitric oxide production and inducible nitric oxide synthase expression in LPS-stimulated RAW264.7 cells. In addition, mRNA and protein expression of proinflammatory cytokines, such as tumor necrosis factor-${\alpha}$ and interleukin-6, was inhibited by proanthocyanidins treatment in LPS-stimulated RAW264.7 cells. These findings support proanthocyanidins as a promising anti-inflammatory agent.

• Journal of Nutrition and Health
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• v.51 no.6
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• pp.489-497
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• 2018

Purpose: Obesity is often associated with disturbances in the mineral metabolism. The purpose of this study was to investigate the effects of high-fat diet-induced obesity on tissue zinc concentrations and zinc transporter expressions in mice. Methods: C57BL/6J male mice were fed either a control diet (10% energy from fat, control group) or a high-fat diet (45% energy from fat, obese group) for 15 weeks. The zinc concentrations in the serum, stool, and various tissues were measured by inductively coupled plasma (ICP)-atomic emission spectrophotometry or ICP-mass spectrophotometry. The levels of zinc transporter mRNAs in the liver, duodenum, and pancreas were measured by real-time RT-PCR. The levels of serum adipokines, such as leptin and IL-6, were determined. Results: The total body weight, adipose tissue weight, and hepatic TG and cholesterol concentrations were significantly higher in the obese group, as compared to the control group. The obese group had significantly higher levels of serum leptin and pro-inflammatory IL-6 concentrations, and had significantly lower levels of serum alkaline phosphatase activity. The zinc concentrations of the liver, kidney, duodenum, and pancreas were all significantly lower in the obese group than in the control group. On the other hand, the fecal zinc concentrations were significantly higher in the obese group than in the control group. The serum zinc concentrations were not significantly different between the two groups. The ZnT1 mRNA levels of the liver and the pancreas were significantly higher in the obese group, as compared to the control group. Hepatic Zip10 mRNA was also increased in the obese group. Conclusion: Our study findings suggest that obesity increases fecal zinc excretion and lowers the tissue zinc concentrations, which may be associated with alterations in the zinc transporter expressions.

• Korean Journal of Food Science and Technology
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• v.51 no.1
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• pp.81-89
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• 2019

This study was performed to confirm the influence of chlorogenic acid (CGA) and 3,5-dicaffeyolquinic acid (3,5-diCQA) intake on problems caused by high-fat diet. CGA was more effective in suppressing weight gain than 3,5-diCQA. In contrast, 3,5-diCQA was more effective in improving glucose tolerance than CGA. In the biopsy, it was confirmed that CGA inhibited visceral fat and liver fat accumulation. 3,5-diCQA also inhibited visceral fat accumulation, but 3,5-diCQA increased liver fat accumulation. The liver fat accumulation induced oxidative stress, but 3,5-diCQA reduced oxidative damage through its antioxidant activity. The increased liver fat accumulation was because a 3,5-diCQA greatly increased Akt phosphorylation and decreased AMPK phosphorylation in the liver. Consequently, CGA was effective in alleviating the problems caused by high-fat diets, while maintaining normal balance. 3,5-diCQA also showed a positive effect on problems caused by high-fat diets, but it increased liver fat accumulation and thereby had negative consequences.

• Korean Journal of Food Science and Technology
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• v.51 no.4
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• pp.379-392
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• 2019

The current study investigated the effect of Gabjubaekmok (Diospyros kaki) ethanolic extract (GEE) on $H_2O_2$-induced human neuroblastoma MC-IXC cells and amyloid beta $(A{\beta})_{1-42}$-induced ICR (Institute of Cancer Research) mice. GEE showed significant antioxidant activity that was evaluated based on ABTS, DPPH scavenging activity, and inhibition of malondialdehyde (MDA) and acetylcholinesterase activity. Further, GEE inhibited ROS production and increased cell viability in $H_2O_2$-induced MC-IXC cells. Administration of GEE ameliorated the cognitive dysfunction on $A{\beta}$-induced ICR mice as evaluated using Y-maze, passive avoidance, and Morris water maze tests. Results of ex vivo test using brain tissues showed that, GEE protected the cholinergic system and mitochondrial functions by increasing the levels of antioxidants such as ROS, mitochondrial membrane potential (MMP), and adenosine triphosphate (ATP) against $A{\beta}$-induced cognitive dysfunction. Moreover, GEE decreasd the expression levels of apoptosis-related proteins such as $TNF-{\alpha}$, p-JNK, p-tau, BAX and caspase 3. While, expression levels of p-Akt and $p-GSK3{\beta}$ increased than $A{\beta}$ group. Finally, gallic acid was identified as the main compound of GEE using high performance liquid chromatography.

• Journal of Life Science
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• v.30 no.12
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• pp.1092-1100
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• 2020

The six-transmembrane epithelial antigen of prostate 4 (Steap4) is a metalloreductase that plays a role in intracellular iron and cupper homeostasis, inflammatory response, and glucose and lipid metabolism. Previously, Steap4 has been reported to stimulate adipocyte differentiation; however, the underlying mechanisms of this action remain unexplored. In the present study, we investigated the molecular mechanisms involved in Steap4-induced adipocyte differentiation using 3T3-L1 cells, immortalized brown adipocyte (iBA) cells, and mouse embryonic fibroblast C3H10T1/2 cells. The knockdown of Steap4 using adenovirus-containing shRNA attenuated mitotic clonal expansion (MCE), as evidenced by the impaired proliferation of 3T3-L1 cells, iBA cells, and C3H10T1/2 cells within 48 hr after adding the differentiation medium. Steap4 knockdown downregulated G1/S phase transition-related cell cycle regulators (including cyclin A and cyclin D) and upregulated cell cycle inhibitors (including p21 and p27). Furthermore, Steap4 knockdown inhibited the phosphorylation of p38 mitogen-activated protein kinase, extracellular signal-regulated kinase, and Akt. Moreover, Steap4 knockdown repressed the expression of early adipogenic activators, such as CCAAT-enhancer-binding protein β (C/EBPβ) and Kruppel-like factor family factor 4 (KLF4). On the other hand, Steap4 knockdown stimulated the expression of adipogenic inhibitors, including KLF2, KLF3, and GATA2. The overexpression of Steap4 using an adenovirus removed the repressive histone marks H3K9me2 and H3K9me3 on the promoter of C/EBPβ. These results indicate that Stepa4 stimulates adipocyte differentiation through the induction of MCE and the modulation of early adipogenic transcription factors, including C/EBPβ, during the early phase of adipocyte differentiation.

• Journal of Life Science
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• v.32 no.7
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• pp.532-541
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• 2022

Obesity induced by high-fat diet (HFD) is verified as a strong risk factor and negative prognostic factor for prostate cancer in several genetically engineered mice although it was not examined in the normal mice. To investigate whether HFD-induced obesity can affect the development and progression of cancer in the prostate of normal mice, alterations in the weight and histological structure of the prostate as well as the expression of cancer-related proteins were analyzed in obese C57BL/6N mice fed with 60% HFD for 16 weeks. First, HFD-induced obesity, including an increase in organ weight, body weight, fat accumulation, and serum lipid profile, was successfully induced in C57BL/6N mice after HFD treatment. The total weight of the prostate significantly increased HFD-induced obesity in the model mice compared with the control group. Among the four lobes of the prostate, the weight of the ventral prostate (VP) and anterior prostate (AP) were higher in HFD-induced obesity model mice than in the control group, although the weights of the lateral prostate (DLP) and seminal vesicle (SV) were constantly maintained. In addition, the incidences of hyperplasia and non-hodgkin's lymphoma (NHL) in the histological structure were remarkably increased in HFD-induced obesity model mice, while the epithelial thickness was higher in the same group. A significant increase in the phosphorylation levels of key proteins in the AKT (protein kinase B) signaling pathway was detected in HFD-induced obesity model mice. Therefore, these results suggest that HFD-induced obesity can promote hyperplasia and NHL in the prostates of C57BL/6N mice through the activation of the AKT signaling pathway.

• Journal of Food Hygiene and Safety
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• v.37 no.3
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• pp.189-197
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• 2022

Asthma is a chronic inflammatory disease characterized by recurring symptoms, airflow obstruction, and bronchial hyper-responsiveness. The onset of asthma for most patients begins early in life, and current asthma treatment with anti-inflammatory agents can have adverse effects, eventually leading to impaired quality of life. In the pathogenesis of asthma, macrophages and basophils play a vital role during progression. Macrophages not only induce inflammation by secreting inflammatory cytokines but also promote DNA damage and mucus production through nitric oxide (NO) production. Basophils enhance eosinophil recruitment and aggravate asthma through the FcεRIα receptor with high affinity for histamine and IgE. Therefore, in this study, we investigated whether the activation of macrophages and basophils is suppressed by the individual extracts of 28 natural products. RAW 264.7 cells (mouse macrophages) were treated with the natural products in LPS, and 4 natural product extracts resulted in decreased NO production. In β-hexosaminidase assay using RBL-2H3 cells (rat basophils), 19 natural product extracts decreased β-hexosaminidase production. In NO production and β-hexosaminidase assay using macrophages and basophils, 3 natural product extracts (Plantago asiatica, Centella asiatica, and Perilla frutescens var. japonica) significantly inhibited NO production and β-hexosaminidase release. Overall, we examined the inhibitory effects of 28 natural product extracts on macrophage and basophil activity, and the findings demonstrated the potential of natural product extracts for treating asthma and macrophage- and basophil-related diseases.

• Journal of Life Science
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• v.32 no.12
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• pp.919-928
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• 2022

As seen in the COVID-19 pandemic, unexpected emergence of new viruses presents serious concern on public health. Especially, the absence of effective vaccines or antiviral drugs against emerging viruses significantly increases the severity of disease and duration of viral circulation among population. Natural products have served as a major source for safe and effective antiviral drugs. In this study, we examined the virucidal activity of medical herb extracts with a view to discover novel antiviral agents with desired levels of safety and antiviral efficacy. Ethanol extracts of ten selected medical herbs were tested for antioxidant activity and in-vitro cytotoxicity in various animal cell lines. Of note, the herbal extracts showed broad and potent virucidal activities against rotavirus, hepatitis A virus, and influenza A virus. The extracts of Sorbus commixta and Glycyrrhiza uralensis showed strong virucidal activities against influenza A virus. We also examined whether the extracts of Sorbus commixta and Glycyrrhiza uralensis can be used as inactivating agents to prepare an inactivated viral vaccine. In a mouse model, influenza A virus inactivated by the extracts elicited high levels of neutralizing antibodies, and the vaccination provided complete protection against lethal challenge. These results suggest that herb-derived natural products can be developed to antiviral drugs as well as inactivating agents for preparation of inactivated viral vaccines.

• Journal of Life Science
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• v.32 no.8
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• pp.601-610
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• 2022

P. tenebrifer (PT) belongs to the Diptera order and Stratiomyidae family. Recently, insect industry have been focused as food, animal feed and environmental advantages. γ-aminobutyric acid (GABA) and melatonin have been associated with regulating sleep and depression. GABA is the primary inhibitory neurotransmitter and is synthesized via biotransformation of monosodium glutamate (MSG) to GABA by lactic acid bacteria. In this study, we first used a GABA-enhanced PT extract, wherein GABA was enhanced by feeding MSG to PT. The underlying mechanisms preventing stress and insomnia were investigated in a corticosterone (CORT)-induced endoplasmic reticulum (ER) stress and chronic restraint stress (CRS)-exposed mouse model, as well as in pentobarbital (45 mg/kg)-induced sleep behaviors in mice. In the present study, the GABA peak was detected in high-performance liquid chromatography-evaporative light scattering detector (HPLC-ELSD) analysis and showed in Ptecticus tenebrifer water extract (PTW) but not in non-PTW extract. The results showed that PTW and Ptecticus tenebrifer with 70% ethanol extract (PTE) exerted neuroprotective effects by protecting against CORT-induced downregulation of phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) and cAMP-response element binding protein (CREB) expression. In addition, PTW (300 mg/kg) significantly reduced CORT levels in CRS-exposed mice. Furthermore, PTW (100 and 300 mg/kg) significantly reduced sleep latency and increased total sleep duration in pentobarbital (45 mg/kg)-induced sleeping behaviors, which was related to serum melatonin levels. In conclusion, our results suggest that PTW exerts anti-stress and sleep-enhancing effects by regulating serum CORT and melatonin levels.