• Title/Summary/Keyword: Sirt 1

검색결과 129건 처리시간 0.028초

Ginsenoside Rb2: A review of pharmacokinetics and pharmacological effects

  • Miao, Longxing;Yang, Yijun;Li, Zhongwen;Fang, Zengjun;Zhang, Yongqing;Han, Chun-chao
    • Journal of Ginseng Research
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    • 제46권2호
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    • pp.206-213
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    • 2022
  • Ginsenoside Rb2 is an active protopanaxadiol-type saponin, widely existing in the stem and leave of ginseng. Rb2 has recently been the focus of studies for pharmaceutical properties. This paper provides an overview of the preclinical and clinical pharmacokinetics for Rb2, which exhibit poor absorption, rapid tissue distribution and slow excretion through urine. Pharmacological studies indicate a beneficial role of Rb2 in the prevention and treatment of diabetes, obesity, tumor, photoaging, virus infection and cardiovascular problems. The underlying mechanism is involved in an inhibition of oxidative stress, ROS generation, inflammation and apoptosis via regulation of various cellular signaling pathways and molecules, including AKT/SHP, MAPK, EGFR/SOX2, TGF-β1/Smad, SIRT1, GPR120/AMPK/HO-1 and NF-κB. This work would provide a new insight into the understanding and application of Rb2. However, its therapeutic effects have not been clinically evaluated. Further studies should be aimed at the clinical treatment of Rb2.

초음파 tomography를 응용한 콘크리트 구조물의 비파괴 시험에 관한 연구 (Application of Ultrasound Tomography for Non-Destructive Testing of Concrete Structure)

  • 김영기;윤영득;윤종열;김정수;김운경;송문호
    • 대한전자공학회논문지SP
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    • 제37권1호
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    • pp.27-36
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    • 2000
  • 본 연구에서는 초음파와 tomography 기법을 기반으로 콘크리트 구조물의 비파괴 시험에 대한 방법론을 정립하고 검증하였다 일반적인 X-ray tomography에서는 물체를 통과하는 파동의 감쇠(attenuation) 데이터에 기초를 두고있는 반면에, 본 연구에서는 time-of-flight(TOF) 데이터를 사용하여 매질의 굴절률(refractive index)을 포괄적으로 표현하는 단층영상을 복원한다 X-ray tomography에서는 측정된 감쇠 데이터를 영상복원(Image reconstruction) 알고리즘에 의해서 처리하며, 파동의 굴절은 고려할 필요가 없다 그러나 초음파는 매질(medium)의 굴절률(refractive index)에 따라 초음파의 경보가 변경되므로 초음파 tomography에서는 초음파 경로의 연산이 선행되어야만 단층영상을 복원할 수 있게 된다 초음파 정보의 연산은 가하광학(Geometrical Optic)에서 사용되는 굴절률과 경로의 관계에 기초를 둔다 영상 복원은 대수학적 접근 방법인 ART (algebraic reconstruction technique) 또는 SIRT(simultaneous iterative reconstruction technique)를 기초로 연산된 초음파의 경로를 따라 선적분한 TOF 값과 측정된 TOF 값의 차이를 기반으로 수행된다 실제 구현에서는 초음파가 직진한다는 가정하에 영상을 복원하고, 이를 기반으로 초음파의 경로를 연산하였다 본 논문에서는 이들 두 과정(경로연산 및 영상복원)의 반복연산을 통하여 영상을 복원하였다. 세안하는 알고리즘을 모의실험으로 평가하였고, 실제 콘크리트 구조물에 적용하여 본 방법론의 무한한 가능성을 입증하였다.

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지반침하지역에서의 탄성파 굴절법 탐사 적용사례 (Case Study on the Seismic Refraction Survey in a Subsidence Area)

  • 윤상호;지준;이두성
    • 한국지반공학회:학술대회논문집
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    • 한국지반공학회 2000년도 가을 학술발표회 논문집
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    • pp.577-584
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    • 2000
  • Seismic refraction survey was peformed for 10 lines along NE-SW and NW-SE directions above Nampoong gallery at Makyo-ri, Dogye, Samcheok, Kangwon-do. 48 geophones were laid in line with the interval of 1m, and a 5Kg hammer was used as a source at 5 points for each line. Data processing was done using reciprocal time method, GRM, and traveltime tomography which utilizes wavefront expansion method for forward process and SIRT for inversion. The result shows that the first layer has its lower boundary between 3.49m and 8.88m. The P-wave velocity of the first and the second layer were estimated as 270 360m/s and 1550 1940m/s respectively. When the boundary of the first and second layer is smooth enough and the velocity difference is large enough, GRM has little advantage over reciprocal time method. The result of reciprocal method and traveltime tomography shows consistency. The northeast part of the boundary has syncline structure, which is similar to the topography above. This implies that the collapse of the cavities of Nampoong gallery result in the subsidence of the ground surface. The subsidence is in progress across the Youngdong railroad, therefore a proper reinforcement work is required.

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균사체 생물전환기술을 이용한 리퀘리티게닌 생산과 항노화 활성 (Production of Liquiritigenin with Cell-based Biotransformation and Its Anti-Aging Activity)

  • 황혜진;정상철;박종필
    • KSBB Journal
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    • 제30권4호
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    • pp.166-174
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    • 2015
  • In this study, an efficient whole cell-based biotransformation for the production of liquiritigenin was developed using Laetiporus sulphureus CS0218 as biocatalyst and aqueous extracts of Glycyrrhiza uralensis as co-substrate, respectively. In order to determine the efficacy of this method, the optimal bioconversion conditions including mycelial growth, three important enzyme activities (${\beta}$-glucosidase, ${\alpha}$-rhamnosidase and ${\beta}$-xylosidase), and apparent viscosity of culture broth were monitored. After optimization, aqueous extracts of G. uralensis were added to the culture medium to directly produce algycone liquiritigenin. By applying this strategy, 67.5% of liquiritin was converted to liquiritigenin at pH 3.0 after 9 days of incubation and finally liquiritigenin was purified from the reaction mixture. And then, their biological activities including anti-oxidant and superoxide dismutase were observed. In fact, purified liquiritigenin was capable of bi-directional functions (i.e., either up-regulation or down-regulation of SIRT1 which is associated with aging). The results indicate that this strategy would be beneficial to produce biologically active liquiritigenin and could be used in pharmaceutical, cosmetic and food applications.

Recombinant Human HAPLN1 Mitigates Pulmonary Emphysema by Increasing TGF-β Receptor I and Sirtuins Levels in Human Alveolar Epithelial Cells

  • Yongwei Piao;So Yoon Yun;Zhicheng Fu;Ji Min Jang;Moon Jung Back;Ha Hyung Kim;Dae Kyong Kim
    • Molecules and Cells
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    • 제46권9호
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    • pp.558-572
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    • 2023
  • Chronic obstructive pulmonary disease (COPD) will be the third leading cause of death worldwide by 2030. One of its components, emphysema, has been defined as a lung disease that irreversibly damages the lungs' alveoli. Treatment is currently unavailable for emphysema symptoms and complete cure of the disease. Hyaluronan (HA) and proteoglycan link protein 1 (HAPLN1), an HA-binding protein linking HA in the extracellular matrix to stabilize the proteoglycan structure, forms a bulky hydrogel-like aggregate. Studies on the biological role of the full-length HAPLN1, a simple structure-stabilizing protein, are limited. Here, we demonstrated for the first time that treating human alveolar epithelial type 2 cells with recombinant human HAPLN1 (rhHAPLN1) increased TGF-β receptor 1 (TGF-β RI) protein levels, but not TGF-β RII, in a CD44-dependent manner with concurrent enhancement of the phosphorylated Smad3 (p-Smad3), but not p-Smad2, upon TGF-β1 stimulation. Furthermore, rhHAPLN1 significantly increased sirtuins levels (i.e., SIRT1/2/6) without TGF-β1 and inhibited acetylated p300 levels that were increased by TGF-β1. rhHAPLN1 is crucial in regulating cellular senescence, including p53, p21, and p16, and inflammation markers such as p-NF-κB and Nrf2. Both senile emphysema mouse model induced via intraperitoneal rhHAPLN1 injections and porcine pancreatic elastase (PPE)-induced COPD mouse model generated via rhHAPLN1-containing aerosols inhalations showed a significantly potent efficacy in reducing alveolar spaces enlargement. Preclinical trials are underway to investigate the effects of inhaled rhHAPLN1-containing aerosols on several COPD animal models.

Extracts of abalone intestine regulates fat metabolism in 3T3-L1 adipocytes and high fat diet-induced zebrafish larvae

  • Laxmi Sen Thakuri;Chul Min Park;Jin Yeong Choi;Hyeon-A Kim;Han Kyu Lim;Jin Woo Park;Dong Wook Kim;Dong Young Rhyu
    • Fisheries and Aquatic Sciences
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    • 제27권2호
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    • pp.122-135
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    • 2024
  • Obesity is a disease involving mechanisms of fat accumulation, low-grade inflammatory cytokine release, and mitochondrial dysfunction. The aim of the current study was to investigate the effects of abalone intestine extract on fat metabolism in 3T3-L1 adipocytes and high fat diet-induced zebrafish larvae. The total phenol content was highest in subcritical water extract at 210℃ (SW210) among hot water, ethanol, and subcritical water extracts of abalone intestine. In addition, SW210 of male abalone intestine (MASW210) most effectively controlled the lipid accumulation and expression of adipogenic or lipogenic regulators (PPAR-γ, C/EBPα, SREBP-1c, and FAS) in 3T3-L1 adipocytes. Likewise, in zebrafish larvae fed high fat, MASW210 significantly suppressed body weight, glucose levels, and lipid accumulation. The mRNA expression related to adipogenesis (PPAR-γ and C/EBPα), lipogenesis (SREBP-1c and FAS), inflammatory cytokines (TNF-α and IL-6), energy m/;.etabolism (AMPK, lepr, SIRT1, and adiponectin), and mitochondrial biogenesis (PGC-1α and CPT-1) were significantly regulated by treatment with MASW210. These results suggest that abalone intestine extract such as MASW210, are useful biomaterials for improving obesity and metabolic diseases.

Korean Red Ginseng attenuates ethanol-induced steatosis and oxidative stress via AMPK/Sirt1 activation

  • Han, Jae Yun;Lee, Sangkyu;Yang, Ji Hye;Kim, Sunju;Sim, Juhee;Kim, Mi Gwang;Jeong, Tae Cheon;Ku, Sae Kwang;Cho, Il Je;Ki, Sung Hwan
    • Journal of Ginseng Research
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    • 제39권2호
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    • pp.105-115
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    • 2015
  • Background: Alcoholic steatosis is the earliest and most common liver disease, and may precede the onset of more severe forms of liver injury. Methods: The effect of Korean Red Ginseng extract (RGE) was tested in two murine models of ethanol (EtOH)-feeding and EtOH-treated hepatocytes. Results: Blood biochemistry analysis demonstrated that RGE treatment improved liver function. Histopathology and measurement of hepatic triglyceride content verified the ability of RGE to inhibit fat accumulation. Consistent with this, RGE administration downregulated hepatic lipogenic gene induction and restored hepatic lipolytic gene repression by EtOH. The role of oxidative stress in the pathogenesis of alcoholic liver diseases is well established. Treatment with RGE attenuated EtOH-induced cytochrome P450 2E1, 4-hydroxynonenal, and nitrotyrosine levels. Alcohol consumption also decreased phosphorylation of adenosine monophosphate-activated protein kinase, which was restored by RGE. Moreover, RGE markedly inhibited fat accumulation in EtOH-treated hepatocytes, which correlated with a decrease in sterol regulatory element-binding protein-1 and a commensurate increase in sirtuin 1 and peroxisome proliferator-activated receptor-a expression. Interestingly, the ginsenosides Rb2 and Rd, but not Rb1, significantly inhibited fat accumulation in hepatocytes. Conclusion: These results demonstrate that RGE and its ginsenoside components inhibit alcoholic steatosis and liver injury by adenosine monophosphate-activated protein kinase/sirtuin 1 activation both in vivo and in vitro, suggesting that RGE may have a potential to treat alcoholic liver disease.

Ursolic acid improves the indoxyl sulfate-induced impairment of mitochondrial biogenesis in C2C12 cells

  • Sasaki, Yutaro;Kojima-Yuasa, Akiko;Tadano, Hinako;Mizuno, Ayaka;Kon, Atsushi;Norikura, Toshio
    • Nutrition Research and Practice
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    • 제16권2호
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    • pp.147-160
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    • 2022
  • BACKGROUND/OBJECTIVES: Patients with chronic kidney disease (CKD) have a high concentration of uremic toxins in their blood and often experience muscle atrophy. Indoxyl sulfate (IS) is a uremic toxin produced by tryptophan metabolism. Although an elevated IS level may induce muscle dysfunction, the effect of IS on physiological concentration has not been elucidated. Additionally, the effects of ursolic acid (UA) on muscle hypertrophy have been reported in healthy models; however, it is unclear whether UA ameliorates muscle dysfunction associated with chronic diseases, such as CKD. Thus, this study aimed to investigate whether UA can improve the IS-induced impairment of mitochondrial biogenesis. MATERIALS/METHODS: C2C12 cells were incubated with or without IS (0.1 mM) and UA (1 or 2 μM) to elucidate the physiological effect of UA on CKD-related mitochondrial dysfunction and its related mechanisms using real-time reverse transcription-polymerase chain reaction, western blotting and enzyme-linked immunosorbent assay. RESULTS: IS suppressed the expression of differentiation marker genes without decreasing cell viability. IS decreased the mitochondrial DNA copy number and ATP levels by downregulating the genes pertaining to mitochondrial biogenesis (Ppargc1a, Nrf1, Tfam, Sirt1, and Mef2c), fusion (Mfn1 and Mfn2), oxidative phosphorylation (Cycs and Atp5b), and fatty acid oxidation (Pdk4, Acadm, Cpt1b, and Cd36). Furthermore, IS increased the intracellular mRNA and secretory protein levels of interleukin (IL)-6. Finally, UA ameliorated the IS-induced impairment in C2C12 cells. CONCLUSIONS: Our results indicated that UA improves the IS-induced impairment of mitochondrial biogenesis by affecting differentiation, ATP levels, and IL-6 secretion in C2C12 cells. Therefore, UA could be a novel therapeutic agent for CKD-induced muscle dysfunction.

모과추출물의 C2C12 근육세포에서 근분화 및 에너지대사조절인자 발현 증진 효과 연구 (Effects of Chaenomelis Fructus Extract on the regulation of myoblasts differentiation and the expression of biogenetic factors in C2C12 myotubes)

  • 강석용;현선영;권예담;박용기;정효원
    • 대한본초학회지
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    • 제34권6호
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    • pp.99-107
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    • 2019
  • Objective : The present study was conducted to investigate the effects of Chaenomelis Fructus (CF) on the regulation of biogenesis in C2C12 mouse skeletal muscle cells. Methods : C2C12 myoblasts were differentiated into myotubes in 2% horse serum-containing medium for 5 days, and then treated with CF extract at different concentrations for 48 hr. The expression of muscle differentiation markers, myogenin and myosin heavy chain (MHC) and mitochondrial biogenesis-regulating factors, peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC1α), sirtuin1 (Sirt1), nuclear respiratory factor1 (NRF1) and transcription factor A, mitochondrial (TFAM), and the phosphorylation of AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) were determined in C2C12 myotubes by reverse transcriptase (RT)-polymerase chain reaction (RT-PCR) and western blot, respectively. The cellular glucose levels and total ATP contents were measured by cellular glucose uptake and ATP assays, respectively. Results : Treatment with CF extract (0.01, 0.02, and 0.05 mg/㎖) significantly increased the expression of MHC protein in C2C12 myotubes compared with non-treated cells. CF extract significantly increased the expression of PGC1α and TFAM in the myotubes. Also, CF extract significantly increased glucose uptake levels and ATP contents in the myotubes. Conclusion : CF extract can stimulate C2C12 myoblasts differentiation into myotubes and increase energy production through upregulation of the expression of mitochondrial biogenetic factors in C2C12 mouse skeletal muscle cell. This suggests that CF can help to improve skeletal muscle function with stimulation of the energy metabolism.

Resveratrol attenuates 4-hydroxy-2-hexenal-induced oxidative stress in mouse cortical collecting duct cells

  • Bae, Eun Hui;Joo, Soo Yeon;Ma, Seong Kwon;Lee, JongUn;Kim, Soo Wan
    • The Korean Journal of Physiology and Pharmacology
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    • 제20권3호
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    • pp.229-236
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    • 2016
  • Resveratrol (RSV) may provide numerous protective effects against chronic inflammatory diseases. Due to local hypoxia and hypertonicity, the renal medulla is subject to extreme oxidative stress, and aldehyde products formed during lipid peroxidation, such as 4-hydroxy-2-hexenal (HHE), might be responsible for tubular injury. This study aimed at investigating the effects of RSV on renal and its signaling mechanisms. While HHE treatment resulted in decreased expression of Sirt1, AQP2, and nuclear factor erythroid 2-related factor 2 (Nrf2), mouse cortical collecting duct cells (M1) cells treated with HHE exhibited increased activation of p38 MAPK, extracellular signal regulated kinase (ERK), c-Jun N-terminal kinase (JNK), and increased expression of NOX4, $p47^{phox}$, Kelch ECH associating protein 1 (Keap1) and COX2. HHE treatment also induced $NF-{\kappa}B$ activation by promoting $I{\kappa}B-{\alpha}$ degradation. Meanwhile, the observed increases in nuclear $NF-{\kappa}B$, NOX4, $p47^{phox}$, and COX2 expression were attenuated by treatment with Bay 117082, N-acetyl-l-cysteine (NAC), or RSV. Our findings indicate that RSV inhibits the expression of inflammatory proteins and the production of reactive oxygen species in M1 cells by inhibiting $NF-{\kappa}B$ activation.