• Journal of Microbiology and Biotechnology
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• v.34 no.3
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• pp.606-621
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• 2024

This study evaluated the hepatoprotective effect of fermented Protaetia brevitarsis larvae (FPB) in ethanol-induced liver injury mice. As a result of amino acids in FPB, 18 types of amino acids including essential amino acids were identified. In the results of in vitro tests, FPB increased alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) activities. In addition, FPB treatment increased cell viability on ethanol- and H₂O₂-induced HepG2 cells. FPB ameliorated serum biomarkers related to hepatoxicity including glutamic oxaloacetic transaminase, glutamine pyruvic transaminase, total bilirubin, and lactate dehydrogenase and lipid metabolism including triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. Also, FPB controlled ethanol metabolism enzymes by regulating the protein expression levels of ADH, ALDH, and cytochrome P450 2E1 in liver tissue. FPB protected hepatic oxidative stress by improving malondialdehyde content, reduced glutathione, and superoxide dismutase levels. In addition, FPB reversed mitochondrial dysfunction by regulating reactive oxygen species production, mitochondrial membrane potential, and ATP levels. FPB protected ethanol-induced apoptosis, fatty liver, and hepatic inflammation through p-AMP-activated protein kinase and TLR-4/NF-κB signaling pathways. Furthermore, FPB prevented hepatic fibrosis by decreasing TGF-β1/Smad pathway. In summary, these results suggest that FPB might be a potential prophylactic agent for the treatment of alcoholic liver disease via preventing liver injury such as fatty liver, hepatic inflammation due to chronic ethanol-induced oxidative stress.

• Journal of Life Science
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• v.33 no.4
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• pp.343-348
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• 2023

Acne is one of the most common skin diseases, mainly occurring in adolescence. The pathophysiology of acne involves not only hormonal, genetic and environmental factors, but also other factors including hyperseborrhea, inflammation, over-keratinization of follicular keratinocytes and overgrowth of Cutibacterium acnes (C. acnes). Cannabidiol (CBD) is known to relieve pain, stress and inflammation. Moreover, cannabis extracts containing CBD have been reported to be effective in treating acne. However, the therapeutic effect of CBD on acne remains unclear. Therefore, this study aimed to investigate the effect and mechanism of CBD on lipogenesis in SEB-1 sebocytes. We treated sebocytes with CBD and found that it not only inhibited lipid synthesis, but also inhibited cell proliferation by inducing apoptosis. We then demonstrated that sterol response element-binding protein-1 (SREBP-1) mediates the inhibitory effect of CBD on lipogenesis. Furthermore, Akt and adenosine monophosphate-activated protein kinase (AMPK), upstream regulators of SREBP-1, were regulated by CBD treatment. Taken together, our studies demonstrate that CBD inhibits adipogenesis by regulating the Akt/AMPK-SREBP-1 signaling pathway, providing potential for use as a therapeutic agent for acne. Further research is needed to confirm the effect of CBD on inflammation caused by hyperkeratosis, which will increase the possibility of using CBD for acne treatment.

• Korean Journal of Exercise Nutrition
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• v.16 no.2
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• pp.65-71
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• 2012

Oxygen is the final acceptor of electron transport from fat and carbohydrate oxidation, which is the rate-limiting factor for cellular ATP production. Under altitude hypoxia condition, energy reliance on anaerobic glycolysis increases to compensate for the shortfall caused by reduced fatty acid oxidation [1]. Therefore, training at altitude is expected to strongly influence the human metabolic system, and has the potential to be designed as a non-pharmacological or recreational intervention regimen for correcting diabetes or related metabolic problems. However, most people cannot accommodate high altitude exposure above 4500 M due to acute mountain sickness (AMS) and insulin resistance corresponding to a increased levels of the stress hormones cortisol and catecholamine [2]. Thus, less stringent conditions were evaluated to determine whether glucose tolerance and insulin sensitivity could be improved by moderate altitude exposure (below 4000 M). In 2003, we and another group in Austria reported that short-term moderate altitude exposure plus endurance-related physical activity significantly improves glucose tolerance (not fasting glucose) in humans [3,4], which is associated with the improvement in the whole-body insulin sensitivity [5]. With daily hiking at an altitude of approximately 4000 M, glucose tolerance can still be improved but fasting glucose was slightly elevated. Individuals vary widely in their response to altitude challenge. In particular, the improvement in glucose tolerance and insulin sensitivity by prolonged altitude hiking activity is not apparent in those individuals with low baseline DHEA-S concentration [6]. In addition, hematopoietic adaptation against altitude hypoxia can also be impaired in individuals with low DHEA-S. In short-lived mammals like rodents, the DHEA-S level is barely detectable since their adrenal cortex does not appear to produce this steroid [7]. In this model, exercise training recovery under prolonged hypoxia exposure (14-15% oxygen, 8 h per day for 6 weeks) can still improve insulin sensitivity, secondary to an effective suppression of adiposity [8]. Genetically obese rats exhibit hyperinsulinemia (sign of insulin resistance) with up-regulated baseline levels of AMP-activated protein kinase and AS160 phosphorylation in skeletal muscle compared to lean rats. After prolonged hypoxia training, this abnormality can be reversed concomitant with an approximately 50% increase in GLUT4 protein expression. Additionally, prolonged moderate hypoxia training results in decreased diffusion distance of muscle fiber (reduced cross-sectional area) without affecting muscle weight. In humans, moderate hypoxia increases postprandial blood distribution towards skeletal muscle during a training recovery. This physiological response plays a role in the redistribution of fuel storage among important energy storage sites and may explain its potent effect on changing body composition. Conclusion: Prolonged moderate altitude hypoxia (rangingfrom 1700 to 2400 M), but not acute high attitude hypoxia (above 4000 M), can effectively improve insulin sensitivity and glucose tolerance for humans and antagonizes the obese phenotype in animals with a genetic defect. In humans, the magnitude of the improvementvaries widely and correlates with baseline plasma DHEA-S levels. Compared to training at sea-level, training at altitude effectively decreases fat mass in parallel with increased muscle mass. This change may be associated with increased perfusion of insulin and fuel towards skeletal muscle that favors muscle competing postprandial fuel in circulation against adipose tissues.

• Journal of the Korean Society of Food Science and Nutrition
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• v.43 no.6
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• pp.829-835
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• 2014

This study investigated the neuroprotective effects of bread containing extract from Cirsium setidens (CS) or Aster scaber (AS) against $H_2O_2$-induced death of human brain neuroblastoma SK-N-SH cells. Treatment with bread containing extract from CS (CSB) or AS (ASB) reduced $H_2O_2$ cytotoxicity in SK-N-SH cells, the intracellular ROS level, and the phospho-p38 mitogen-activated protein kinase (MAPK) level. In the sensory evaluation, wild vegetable flavor scores of CSB were higher than those of ASB and bread containing 0% CS or AS (NB). In terms of appearance, color, flavor, softness, and overall acceptability, CSB and ASB showed higher scores than NB, but no differences were observed between CSB and ASB. These results indicate that CSB and ASB have potent health benefits in terms of neuroprotection against oxidative stress mediated through antioxidant activity and inhibition of p38 phosphorylation in brain neural cells. Thus, CS and AS could be considered as a health functional material.

• Journal of Life Science
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• v.32 no.11
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• pp.865-871
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• 2022

Tenebrio molitor larvae is well known as edible insect. Then, although it has been widely studied that Tenebrio molitor larvae has various bioactive functions such as antioxidant, anti-wrinkle, and anticancer. Nevertheless, antioxidant effects of Tenebrio molitor larvae water extract (TMH) has not been well described in Adult Retina Pigment Epithelial cell line (ARPE-19). In this study, we demonstrated that antioxidant effects of TMH against H₂O₂-induced oxidative stress in ARPE-19. Thus, we selected for our studies and performed a series of dose-response assay to determine the working concentration that lead to a consistent and high degree of cytotoxicity, which we defined as the level of H₂O₂ that killed 40% of the ARPE-19 cells. ARPE-19 cells were pre-treated with various concentrations of TMH (0.1 up to 2 mg/ml) before exposure to 300 µM H₂O₂. As we expected, TMH effectively prevented ARPE-19 cells from 300 µM H₂O₂-induced cell death in a dose-dependent manner. Furthermore, TMH inhibited the phosphorylation of mitogen-activated protein kinases (MAPKs) such as extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and p38. Overall, the inhibitory effects of TMH on H₂O₂-induced apoptosis and oxidative stress were associated with the protection cleaved caspase-3, Bax, Bcl-2, and HO-1. The TMH suppressed H₂O₂-induced cell membrane leakage and oxidative stress in ARPE-19 cells. Thus, these results suggest that the TMH plays an important role in antioxidant effect in ARPE-19.

• Journal of the Korean Society of Food Science and Nutrition
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• v.46 no.8
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• pp.910-918
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• 2017

Hyperlipidemia is known as a glucose and lipid metabolism-related disorder that is increasing in incidence in modern society. Red ginseng (RG) is a natural herb candidate with a positive effect on regulation of cholesterol and lipids. To observe the effects of RG on regulation of lipids, cholesterol, glucose, and oxidative stress, we examined the in vitro and in vivo effects of Chamdahan RG on differentiated 3T3-L1 adipocytes and high-fat diet-fed mice. RG ($50{\mu}g/mL$) significantly inhibited lipid synthesis in 3T3-L1 cells. In addition, a low concentration of RG (880 mg/kg/d) resulted in the lowest total blood cholesterol level. Moreover, high density lipoprotein-cholesterol quantity increased in RG-treated groups, consequently lowering the cardiovascular risk factor and atherosclerosis index. Moreover, RG increased activity of AMP-activated protein kinase, as a regulator of lipid and cholesterol synthesis, in adipose and liver tissues. Cumulatively, this paper suggests that RG has a positive effect on reducing the amounts of cholesterol and lipids and may be a good candidate for treating hyperlipidemia.

• The Journal of Internal Korean Medicine
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• v.25 no.4
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• pp.324-336
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• 2004

Objectives : The purpose of this investigation is to evaluate the effects of Scutellaria baicalensis GEORGI on alteration in gene expression in a hypoxia model using cultured rat cortical cells. Methods : E18 rat cortical cells were grown in a Neurobasal medium containing B27 supplement. On 12 DIV, Scutellaria baicalensis GEORGI(20 ug/ml) was added to the culture media and left for 24 hrs. On 11 DIV, cells were given a hypoxic insult $(2%\;O_2/5%\;CO_2,\;37^{\circ}C,\;3\;hrs)$, returned to normoxia and cultured for another 24 hrs. Total RNA was prepared from Scutellaria baicalensis GEORGI-untreated (control) and -treated cultures and alteration in gene expression was analysed by microarray using rat 5K-TwinChips. Results : For most of the genes altered in expression, the Global M values were between -0.5 to +0.5. Among these, 1143 genes increased in their expression by more than Global M +0.1, while 1161 genes decreased by more than Global M -0.1. Effects on some of the genes whose functions are implicated in neural viability are as follows: 1) The expression of apoptosis-related genes such as Bad (Global M = 0.39), programmed cell death-2(Pdcd2) (Global M = 0.20) increased, while Purinergic receptor P2X(P2rxl) Global M = -0.22), Bc12-like1(Bc1211)(Global M = -0.19) decreased. 2) The expression of 'response to stress-related genes such as antioxidation-related AMP-activated protein kinase subunit gamma 1 gene (Prkag1) (Global M = 0.14), catalase gene (Global M = 0.14) and Heme Oxygenase(Hmoxl) increased. 3) The expression of Fos like antigen 2 (Fos12) expressed in neurons that survive ischemic insult increased (Global M = 0.97). Conclusions : these data suggest that Scutellaria baicalensis GEORGI increases the expression of antiapoptosis- and antioxidation- related genes in a way that can not yet be explained.

• Biomolecules & Therapeutics
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• v.28 no.5
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• pp.443-455
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• 2020

The thioredoxin (Trx) system plays critical roles in regulating intracellular redox levels and defending organisms against oxidative stress. Recent studies indicated that Trx reductase (TrxR) was overexpressed in various types of human cancer cells indicating that the Trx-TrxR system may be a potential target for anti-cancer drug development. This study investigated the synergistic effect of auranofin, a TrxR-specific inhibitor, on sulforaphane-mediated apoptotic cell death using Hep3B cells. The results showed that sulforaphane significantly enhanced auranofin-induced apoptosis by inhibiting TrxR activity and cell proliferation compared to either single treatment. The synergistic effect of sulforaphane and auranofin on apoptosis was evidenced by an increased annexin-V-positive cells and Sub-G1 cells. The induction of apoptosis by the combined treatment caused the loss of mitochondrial membrane potential (ΔΨm) and upregulation of Bax. In addition, the proteolytic activities of caspases (-3, -8, and -9) and the degradation of poly (ADP-ribose) polymerase, a substrate protein of activated caspase-3, were also higher in the combined treatment. Moreover, combined treatment induced excessive generation of reactive oxygen species (ROS). However, treatment with N-acetyl-L-cysteine, a ROS scavenger, reduced combined treatment-induced ROS production and apoptosis. Thereby, these results deduce that ROS played a pivotal role in apoptosis induced by auranofin and sulforaphane. Furthermore, apoptosis induced by auranofin and sulforaphane was significantly increased through inhibition of the phosphoinositide 3-kinase (PI3K)/Akt pathway. Taken together, the present study demonstrated that down-regulation of TrxR activity contributed to the synergistic effect of auranofin and sulforaphane on apoptosis through ROS production and inhibition of PI3K/Akt signaling pathway.

• Journal of Life Science
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• v.26 no.1
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• pp.34-41
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• 2016

Black chokeberries (scientific name Aronia melanocarpa) have been reported to have major effects due to anti-oxidant, anti-inflammatory, and anti-cancer capabilities. In this study, we investigated the anti- wrinkle effects of A. melanocarpa, including collagenase inhibition effects and their molecular biological mechanisms, such as oxidative stress-induced matrix metalloproteinase (MMP), mitogen-activated protein (MAP) kinase, and activator protein (AP)-1 expression and/or phosphorylation. In collagenase inhibition activity, the ethyl acetate fraction of black chokeberry (AE) was 77.2% at a concentration of 500 μg/ml, which was a significant result compared to that of Epigallocatechin gallate (positive control, 83.9% in 500 μg/ml). In the reactive oxygen species (ROS) assay, the AE produced 78% of ROS in 10 μg/ml and 70% of ROS in 75 μg/ml, which was a much lower percentage than the ROS production of H₂O₂-induced CCRF S-180II cells. In the MTT assay, cell viability was increased dose-dependently with AE in H₂O₂-induced cells. In protein expression by western blot assay, the AE suppressed the expression and phosphorylation of MMPs (MMP-1, -3, -9), MAPK (ERK, JNK, and p38), and AP-1 (c-Fos and c-Jun), and expressed the pro-collagen type I in H₂O₂-induced cells. These results suggest that black chokeberries have anti-wrinkle and collagen-production effects, and they may be used in applications for material development in the functional food and cosmetic industries.