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Restorative effects of Rg3-enriched Korean Red Ginseng and Persicaria tinctoria extract on oxazolone-induced ulcerative colitis in mice

  • Ullah, H.M. Arif;Saba, Evelyn;Lee, Yuan Yee;Hong, Seung-Bok;Hyun, Sun-Hee;Kwak, Yi-Seong;Park, Chae-Kyu;Kim, Sung Dae;Rhee, Man Hee
    • Journal of Ginseng Research
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    • v.46 no.5
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    • pp.628-635
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    • 2022
  • Background: Ulcerative colitis (UC) is the large intestine disease that results in chronic inflammation and ulcers in the colon. Rg3-enriched Korean Red Ginseng extract (Rg3-RGE) is known for its pharmacological activities. Persicaria tinctoria (PT) is also used in the treatment of various inflammatory diseases. The aim of this study is to investigate the attenuating effects of Rg3-RGE with PT on oxazolone (OXA)-induced UC in mice. Methods: A total of six groups of mice including control group, OXA (as model group, 1.5%) group, sulfasalazine (75 mg/kg) group, Rg3-RGE (20 mg/kg) group, PT (300 mg/kg) group, and Rg3-RGE (10 mg/kg) with PT (150 mg/kg) group. Data on the colon length, body weight, disease activity index (DAI), histological changes, nitric oxide (NO) assay, Real-time PCR of inflammatory factors, ELISA of inflammatory factors, Western blot, and flow cytometry analysis were obtained. Results: Overall, the combination treatment of Rg3-RGE and PT significantly improved the colon length and body weight and decreased the DAI in mice compared with the treatment with OXA. Additionally, the histological injury was also reduced by the combination treatment. Moreover, the NO production level and inflammatory mediators and cytokines were significantly downregulated in the Rg3-RGE with the PT group compared with the model group. Also, NLR family pyrin domain containing 3 (NLRP3) inflammasome and nuclear factor kappa B (NF-𝛋B) were suppressed in the combination treatment group compared with the OXA group. Furthermore, the number of immune cell subtypes of CD4+ T-helper cells, CD19+ B-cells, and CD4+ and CD25+ regulatory T-cells (Tregs) was improved in the Rg3-RGE with the PT group compared with the OXA group. Conclusion: Overall, the mixture of Rg3-RGE and PT is an effective therapeutic treatment for UC.

Comparison among GGEx16, GGEx18 and gambitongseong-capsule for anti-obesity gene activity (GGEx16, GGEx18과 감비통성교낭(減肥通聖膠囊)의 항비만유전자 활성 비교)

  • Oh, Jaeho;Ahn, Ye Ji;Lee, Hye Rim;Lim, Hyesook;Lee, Hyunghee;Yoon, Michung;Shin, Soon Shik
    • The Korea Journal of Herbology
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    • v.28 no.2
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    • pp.39-44
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    • 2013
  • Objectives : Gambigyeongsinhwan 16 (GGEx16), gambigyeongsinhwan 18 (GGEx18) and gambitongseong capsule are shown to be involved in the regulation of obesity. Therefore, the aim of this study was to compare the reporter activity of anti-obesity genes such as peroxisome proliferator-activated receptor ${\alpha}$ ($PPAR{\alpha}$) and $PPAR{\delta}$ by GGEx16, GGEx18 and gambitongseong capsule. Methods : After NMu2Li liver cells, C2C12 skeletal muscle cells and 3T3-L1 preadipocytes were treated with GGEx16 (1 ${\mu}g/ml$), GGEx18 (1 ${\mu}g/ml$) and different concentrations of gambitongseong capsule, the transactivation of $PPAR{\alpha}$ and $PPAR{\delta}$ was measured by a luciferase reporter gene assay. Results : $PPAR{\alpha}$ reporter gene activity in NMu2Li liver cells and 3T3-L1 preadipocytes was significantly increased by GGEx16, GGEx18 and gambitongseong capsule compared with control, whereas $PPAR{\alpha}$ reporter gene activity in C2C12 skeletal muscle cells was significantly increased by GGEx18 only compared with control. Similarly, $PPAR{\delta}$ reporter gene activity in 3T3-L1 preadipocytes was also significantly increased by GGEx18 compared with control. $PPAR{\delta}$ reporter gene activity in C2C12 skeletal muscle cells was significantly increased by GGEx16 and GGEx18 compared with control although $PPAR{\delta}$ reporter gene activity in NMu2Li liver cells was not changed by these three formulas. Conclusions : These results suggest that all three formulas have the ability to stimulate $PPAR{\alpha}$ and $PPAR{\delta}$ transactivation in animal cell lines with high metabolic rates. In particular, this effects were most prominent in GGEx18-treated cells. In addition, it is likely that GGEx18 may be used as an effective anti-obesity composition.

Antidiabetic effects of unripe black raspberry ethanol extracts in C57BL/6N db/db mice (C57BL/6N db/db 생쥐에서 복분자 미숙과 에탄올 추출물의 항당뇨 효과)

  • Choi, Hye Ran;Lee, Su Jung;Ryu, Tae Ho
    • Korean Journal of Food Science and Technology
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    • v.54 no.4
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    • pp.391-397
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    • 2022
  • This study aimed to verify the antidiabetic effects of the unripe black raspberry extract (UBRE) in obese diabetic mice. For the experiment, animal model mice were divided into six groups: normal control, diabetic control, three experimental groups (treated with 75, 150, and 300 mg/kg single dose of UBRE), and a positive control (200 mg/kg metformin). The groups treated with 300 mg/kg UBRE and metformin had significantly reduced blood glucose and triglyceride levels in the diabetic mice compared to those in the vehicle control group. In addition, histopathological evaluation showed that UBRE increased the Langerhans area, cell number, and insulin concentration in the pancreatic islets of db/db mice. Therefore, UBRE exerts significant antidiabetic effects by decreasing the blood glucose and lipid levels, suggesting that it can be consumed as a functional diet for diabetic patients.

Pathophysiological Functions of Deubiquitinating Enzymes in Obesity and Related Metabolic Diseases (탈유비퀴틴화 효소 DUBs의 비만 및 대사 관련 질환에서 병태생리학적 기능)

  • Lee, Seul Gi;Kwon, Taeg Kyu
    • Journal of Life Science
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    • v.32 no.6
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    • pp.476-481
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    • 2022
  • Ubiquitin signaling regulates virtually all aspects of eukaryotic biology and dynamic processes in which protein substrates are modified by ubiquitin. To regulate these processes, deubiquitinating enzymes (DUBs) cleave ubiquitin or ubiquitin-like proteins from these substrates. DUBs have been implicated in the pathogenesis of cancer, leading to the development of increasing numbers of small-molecule DUB inhibitors. On the other hand, recent studies have focused on the function of DUBs in metabolic diseases such as obesity, diabetes, and fatty liver diseases. DUBs play a positive or negative role in the progression and development of metabolic diseases. Their involvement in cell pathology and regulation of major transcription factors in metabolic syndrome has been examined in vitro and in animal and human biopsies. UCH, USP7, and USP19 were linked to adipocyte differentiation, body weight gain, and insulin resistance in genetic or diet-induced obesity. CYLD, USP4, and USP18 were found to be closely associated with fatty liver diseases. In addition, these liver diseases were accompanied by body weight change in certain cases. Collectively, in this review, we discuss the current understanding of DUBs in metabolic diseases with a particular focus on obesity. We also provide basic knowledge and regulatory mechanisms of DUBs and suggest these enzymes as therapeutic targets for metabolic diseases.

Ginsenoside Rg3 ameliorates myocardial glucose metabolism and insulin resistance via activating the AMPK signaling pathway

  • Ni, Jingyu;Liu, Zhihao;Jiang, Miaomiao;Li, Lan;Deng, Jie;Wang, Xiaodan;Su, Jing;Zhu, Yan;He, Feng;Mao, Jingyuan;Gao, Xiumei;Fan, Guanwei
    • Journal of Ginseng Research
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    • v.46 no.2
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    • pp.235-247
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    • 2022
  • Background: Ginsenoside Rg3 is one of the main active ingredients in ginseng. Here, we aimed to confirm its protective effect on the heart function in transverse aortic coarctation (TAC)-induced heart failure mice and explore the potential molecular mechanisms involved. Methods: The effects of ginsenoside Rg3 on heart and mitochondrial function were investigated by treating TAC-induced heart failure in mice. The mechanism of ginsenoside Rg3 for improving heart and mitochondrial function in mice with heart failure was predicted through integrative analysis of the proteome and plasma metabolome. Glucose uptake and myocardial insulin sensitivity were evaluated using micro-positron emission tomography. The effect of ginsenoside Rg3 on myocardial insulin sensitivity was clarified by combining in vivo animal experiments and in vitro cell experiments. Results: Treatment of TAC-induced mouse models with ginsenoside Rg3 significantly improved heart function and protected mitochondrial structure and function. Fusion of metabolomics, proteomics, and targeted metabolomics data showed that Rg3 regulated the glycolysis process, and Rg3 not only regulated glucose uptake but also improve myocardial insulin resistance. The molecular mechanism of ginsenoside Rg3 regulation of glucose metabolism was determined by exploring the interaction pathways of AMPK, insulin resistance, and glucose metabolism. The effect of ginsenoside Rg3 on the promotion of glucose uptake in IR-H9c2 cells by AMPK activation was dependent on the insulin signaling pathway. Conclusions: Ginsenoside Rg3 modulates glucose metabolism and significantly ameliorates insulin resistance through activation of the AMPK pathway.

A Bivalent Inactivated Vaccine Prevents Enterovirus 71 and Coxsackievirus A16 Infections in the Mongolian Gerbil

  • Eun-Je Yi;Young-In Kim;Seung-Yeon Kim;Sung Hyun Ahn;Hyoung Jin Lee;Bohyun Suh;Jaelim Yu;Jeehye Park;Yoon Jung Lee;Eunju Jung;Sun-Young Chang
    • Biomolecules & Therapeutics
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    • v.31 no.3
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    • pp.350-358
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    • 2023
  • Hand-foot-and-mouth disease (HFMD) is a viral infectious disease that occurs in children under 5 years of age. Its main causes are coxsackievirus (CV) and enterovirus (EV). Since there are no efficient therapeutics for HFMD, vaccines are effective in preventing the disease. To develop broad coverage against CV and EV, the development of a bivalent vaccine form is needed. The Mongolian gerbil is an efficient and suitable animal model of EV71 C4a and CVA16 infection used to investigate vaccine efficacy following direct immunization. In this study, Mongolian gerbils were immunized with a bivalent inactivated EV71 C4a and inactivated CVA16 vaccine to test their effectiveness against viral infection. Bivalent vaccine immunization resulted in increased Ag-specific IgG antibody production; specifically, EV71 C4a-specific IgG was increased with medium and high doses and CVA16-specific IgG was increased with all doses of immunization. When gene expression of T cell-biased cytokines was analysed, Th1, Th2, and Th17 responses were found to be highly activated in the high-dose immunization group. Moreover, bivalent vaccine immunization mitigated paralytic signs and increased the survival rate following lethal viral challenges. When the viral RNA content was determined from various organs, all three doses of bivalent vaccine immunization were found to significantly decrease viral amplification. Upon histologic examination, EV71 C4a and CVA16 induced tissue damage to the heart and muscle. However, bivalent vaccine immunization alleviated this in a dose-dependent manner. These results suggest that the bivalent inactivated EV71 C4a/CVA16 vaccine could be a safe and effective candidate HFMD vaccine.

NDP Kinases Suppressed Bax-Dependent Apoptosis in Yeast System

  • K. C. Hwang;D. W. Ok;D. N. Kwon;H. K. Shin;Kim, J. H.
    • Proceedings of the KSAR Conference
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    • 2001.03a
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    • pp.52-52
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    • 2001
  • Many nucleoside diphosphate (NDP) kinases are ubiquitous enzymes responsible for the exchange of ${\gamma}$-phosphates between tri- and diphosphonucleosides. The catalytic Many nucleoside diphosphate (NDP) kinases are ubiquitous enzymes responsible for the exchange of ${\gamma}$-phosphates between tri- and diphosphonucleosides. The catalytic reaction follows a ping-pong mechanism in which the enzyme is transiently phosphorylated on a histidine residue conserved in all nucleoside diphosphate kinases. Beside their role in nucleotide synthesis, these enzymes present additional functions, possibly independent of catalysis, in processes such as differentiation, cell growth, tumor progression, metastasis and development. To clone murine nm23-M5, several expressed sequence tags (ESTs) of the GenBank data base, selected according to their homology to nm23-H5 cDNA, reconstituted a complete open reading frame (GenBank AF222750). To test whether murine NDPKs (1, 2, 3, 4, 5, and 6) can inhibit Bax-mediated toxicity in yeast, co-transformation was performed respectively. The yeast S.cerevisiae was transformed with a copy expression plasmid containing the histidine selection marker and expressing murine Bax under the control of a galactose-inducible promoter. Several clones were selected and found to be growth inhibited when Bax expression was induced with galactose. A representative clone was transformed again with a copy expression plasmid containing the tryptophane selection marker and expressing either murine Bcl-xL or NDPK under the control of a galactose-inducible promoter. Several subclones of the double-transformants were selected and characterized. The ability of Bcl-xL and NDPKs to suppress Bax-mediated toxicity was determined by growing yeast cells overnight in galactose media and spot-testing on galactose plates starting with an equal number of yeast cells as determined by taking the OD$_{600}$. Ten-fold serial dilutions were used in the spot-test. Plates were grown at 3$0^{\circ}C$ for 2-3 days. All murine NDPKs suppressed Bax dependent apoptosis. Futher study will be peformed whether Bax-toxicity inhibition was caused by NDP kinase activity or additional function.n.

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Development and Evaluation of Children's Smart Photonic Safety Clothing ( 어린이의 스마트 포토닉 안전의복의 개발 및 평가)

  • Soon-Ja Park;Dae-jin, Ko;Sung-eun, Jang
    • Science of Emotion and Sensibility
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    • v.26 no.2
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    • pp.129-140
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    • 2023
  • Following ISO 20471, in this study, first, two sets of safety clothes and safety vests were made by designing and attaching animal and bird patterns preferred by children to retroreflective films and black fabrics on those fluorescent fabrics and retroreflective materials prescribed by international standards. Second, by mounting a smart photonic device on the safety clothing so that the body can be recognized from a distance even without an ambient light source at night, children can emit three types of light depending on the situation with just one-touch of the button. From a result of comparison with visibility a day and night by dressing a mannequin in the made smart safety clothing, the difference in visibility was evident at night, it was confirmed that we can see the figure of a person even at a distance of approximately 70 m. Therefore, it is expected to contribute to the prevention of traffic and other accidents on the road, as the drivers driving at night or in bad weather can recognize a person from a distance. Third, in case of the energy is exhausted and cannot maintain the stability of the light-emitting function of the optical faber, we can use energy harvesting device, and the light-emitting time will be extended. As a result it comes up to emit light stably for a long time. And this prove that smart photonic safety clothing can also be used for night workers. Therefore, optical fiber safety clothing is expected to be highly wearable not only in real life but also in dark industrial sites due to stable charging by applying the energy harvesting provided by solar cells.

Evaluation of Biological Activity of Veronica incana Extracts (Veronica incana 추출물의 생물학적 활성 평가)

  • Mi-Rae Shin;Mi Yeong Yoon;Min Ju Kim;Il-Ha Jeong;Hui Yeon An;Ji-Won Jung;Seong-Soo Roh
    • The Korea Journal of Herbology
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    • v.39 no.3
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    • pp.57-67
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    • 2024
  • Objectives : The aim of this study is to evaluate the potential biological activity of Veronica incana extracts (VIE) through in vitro, ex vivo, and in vivo experiments. Methods : In vitro, we conducted analyses on the total polyphenol (TP) and total flavonoid (TF) levels, alongside DPPHand ABTS radical scavenging activities. Ex vivo evaluations on adipose tissue measured glycerol release as a marker of lipolysis. In LPS-induced RAW 264.7 cells, we quantified nitric oxide (NO) production. Following H2O2 induction in U2OS cells, we performed mitochondrial assays such as MitoSox and MitoTracker. Moreover, Bodipy assays were conducted in 3T3-L1 cells. In vivo, we performed anti-osteoarthritis effect of VIE against monosodium iodoacetate (MIA)-induced osteoarthritis in rats. Results : The results presented encompass a myriad of models, from cell culture to animal experiments as well as ex vivo studies. VIE demonstrated high TP and TF contents, potent DPPH and ABTS scavenging activities, and regulated glycerol release. Moreover, the inhibition of NO production in LPS-induced inflammation was notably confirmed and the reduction of lipid droplets was distinctly shown. Furthermore, in H2O2-induced U2OS cells, MitoSox was effectively reduced while MitoTracker noticeably increased. In vivo assays confirmed a significant increase in hindpaw weight distribution (HWD) decreased by MIA after VIE treatment. Additionally, VIE inhibited serum inflammatory cytokines (TNF-𝛼, IL-6, and IL-1𝛽) and MDA levels in joint tissue. Conclusion : In conclusion, Veronica incana exhibited various pharmacological effects including antioxidant, anti-obesity, and anti-inflammatory properties.

Requirement of β subunit for the reduced voltage-gated Na+ current of a Brugada syndrome patient having novel double missense mutation (p.A385T/R504T) of SCN5A

  • Na Kyeong Park;Seong Woo Choi;Soon-Jung Park;JooHan Woo;Hyun Jong Kim;Woo Kyung Kim;Sung-Hwan Moon;Hun-Jun Park;Sung Joon Kim
    • The Korean Journal of Physiology and Pharmacology
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    • v.28 no.4
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    • pp.313-322
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    • 2024
  • Mutations within the SCN5A gene, which encodes the α-subunit 5 (NaV1.5) of the voltage-gated Na+ channel, have been linked to three distinct cardiac arrhythmia disorders: long QT syndrome type 3, Brugada syndrome (BrS), and cardiac conduction disorder. In this study, we have identified novel missense mutations (p.A385T/R504T) within SCN5A in a patient exhibiting overlap arrhythmia phenotypes. This study aims to elucidate the functional consequences of SCN5A mutants (p.A385T/R504T) to understand the clinical phenotypes. Whole-cell patch-clamp technique was used to analyze the NaV1.5 current (INa) in HEK293 cells transfected with the wild-type and mutant SCN5A with or without SCN1B co-expression. The amplitude of INa was not altered in mutant SCN5A (p.A385T/R504T) alone. Furthermore, a rightward shift of the voltage-dependent inactivation and faster recovery from inactivation was observed, suggesting a gain-of-function state. Intriguingly, the co-expression of SCN1B with p.A385T/R504T revealed significant reduction of INa and slower recovery from inactivation, consistent with the loss-of-function in Na+ channels. The SCN1B dependent reduction of INa was also observed in a single mutation p.R504T, but p.A385T co-expressed with SCN1B showed no reduction. In contrast, the slower recovery from inactivation with SCN1B was observed in A385T while not in R504T. The expression of SCN1B is indispensable for the electrophysiological phenotype of BrS with the novel double mutations; p.A385T and p.R504T contributed to the slower recovery from inactivation and reduced current density of NaV1.5, respectively.