• Title/Summary/Keyword: stimulatory effect

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Effect of Kenpaullone, a Specific Inhibitor of GSK3${\beta}$, on Melanin Synthesis in B16 Melanoma and Human Melanocytes (GSK3${\beta}$의 선택적 저해제인 Kenpaullone의 B16 멜라노마 및 인간 멜라노사이트에서의 영향)

  • Kim, Hae-Jong;Lee, You-Ree;Nguyen, Dung Hoang;Lee, Hyang-Bok;Kim, Eun-Ki
    • Journal of the Society of Cosmetic Scientists of Korea
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    • v.37 no.3
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    • pp.211-218
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    • 2011
  • Effects of Kenpaullone, a specific inhibitor of GSK3${\beta}$, on melanin synthesis in B16 melanoma cells and human melanocytes were investigated. Kenpaullone showed a melanogenesis stimulation activity in a concentrationdependent manner in murine B16 melanoma cells and human melanocytes without any significant effects on cell proliferation. Tyrosinase activity was increased 48 h after treatment of B16 cells with Kenpaullone. The protein expression level of tyrosinase was dose-dependently enhanced after the treatment with Kenpaullone. At the same time, the expression level of tyrosinase mRNA was also increased after addition of Kenpaullone. The stimulatory effect of Kenpaullone mainly resulted from increased expression of tyrosinase. These findings suggest that the application of GSK3${\beta}$ inhibitors may be a potential therapeutic agent for the treatment of hypopigmentation disorder.

Plasma Gastrin Concentration after a Carbohydrate Meal and a Protein Meal in Normal Human Subjects (식후 정상 한국인의 혈장 gastrin 농도)

  • Kim, Myung-Suk;Park, Hyoung-Jin;Jo, Yang-Hyeok;Kwon, Kyoung-Ok;Lee, Yoon-Lyeur
    • The Korean Journal of Physiology
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    • v.15 no.2
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    • pp.83-89
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    • 1981
  • This study was conducted to investigate the effect of the ingestion of rice and hamburger meals upon the plasma gastrin concentration in normal human subjects in Korea. Eight normal human subjects including male and female with the mean age of 28 years (range: 20-40 years) were studied. After an overnight(about 15 hrs) fast each subject ingested a rice meal and a hamburger meal on different days. The rice meal consisted of 250 g boiled rice, 50 g vegetables and 200 ml barley tea, corresponding to 6.8 g protein, 0.5 g fat and 81g carbohydrate and the hamburger meal consisted of 200 g hamburger, 50 g vegetables ana 200 ml milk, corresponding to 43 g protein, 43 g fat and 9 g carbohydrate. The venous blood samples were drawn before and after the ingestion of the test meal at the following times: -30, 0, 15, 30, 45, 60, 90, and 120 min, for measurement of gastrin by radioimmunoassay. The following results were obtained : 1) Plasma gastrin concentration in response to the ingestion of the rice or the hamburger meal increased significantly compared with the concentration in fasting state. 2) The increase of the plasma gastrin concentration after the hamburger meal was significantly higher than that after the rice meal. 3) There was a significant linear correlation between the postprandial peak plasma gastrin concentration after the rice meal and the concentration after the hamburger meal in each subject. It is inferred from the above results that a carbohydrate meal as well as a protein meal has a stimulatory effect on gastrin release in normal human subjects.

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Anti-neuroinflammatory effects of cultivated red ginseng with fermented complex mushroom-cereal mycelium on lipopolysaccharide activated BV2 microglial cells (LPS로 인해 활성화된 BV2 Microglia에서 발효 복합버섯-곡물 숙성균주 배양 홍삼(紅蔘)의 뇌신경염증 보호효과)

  • Bitna, Kweon;Jin-Young, Oh;Dong-Uk, Kim;Mi-Kyung, Jang;Jun-Hyoung, Cho;Sung-Joo, Park;Gi-Sang, Bae
    • The Korea Journal of Herbology
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    • v.38 no.1
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    • pp.11-19
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    • 2023
  • Objectives : Neuroinflammation is a common pathological mechanism of neurodegenerative diseases, and the development of therapeutic agents is urgently needed. Red ginseng has been known to be good for the immune stimulation in Eastern Asia. Although the immuno-stimulatory activity of red ginseng are already known, the neuro-protective effects of cultivated red ginseng with fermented complex mushroom-cereal mycelium (RGFM) have not been conducted. Thus, in this study, we tried to investigate the anti-neuroinflammatory effect of RGFM water extract on lipopolysaccharide (LPS) stimulated BV2 cells. Methods : BV2 cells were pretreated with RGFM 1 h prior to LPS exposure. To determine the neuro-protective effects of RGFM water extract, we measured the expression of inflammatory mediators including inducible nitric oxide synthase (iNOS), cyclooxygenase (COX)-2 and nitric oxide (NO) and pro-inflammatory cytokines such as interleukin (IL)-1𝛽, IL-6 and tumor necrosis factor (TNF)-𝛼 in LPS-stimulated BV2 cells. In addition, to find out the regulatory mechanism of RGFM water extract, we assessed the protein levels of mitogen-activated protein kinases (MAPKs) and inhibitory 𝜅B𝛼 (I𝜅B𝛼) by western blotting. Results : In our study, treatment of RGFM reduced the mRNA expression of iNOS and COX-2 and suppressed NO production in LPS-stimulated BV2 cells. Additionally, the secretion of IL-1𝛽 and TNF-𝛼 but not IL-6 was significantly inhibited by RGFM. Furthermore, RGFM water extract inhibited the phosphorylation of c-Jun N-terminal kinase (JNK). Conclusions : Taken together, these findings suggest that RGFM water extract has a protective effect on neuroinflammation through inhibition of JNK.

Effects of $TGF-{\beta}1$ on Cellular Activity of Minocycline-Pretreated Human Periodontal Ligament Cells (($TGF-{\beta}$)이 Minocycline을 전처리한 사람 치주인대세포의 활성에 미치는 영향)

  • Yang, Seung-Oh;You, Hyung-Keun;Shin, Hyung-Shik
    • Journal of Periodontal and Implant Science
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    • v.26 no.2
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    • pp.469-490
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    • 1996
  • The initial events required for periodontal regeneration is the attachment, spreading, and proliferation of appropriated cells at the healing sites. These have been reported that minocycline stimulates the attachment of periodontal ligament cells, and also $TGF-{\beta}1$ enhances the proliferation of periodontal ligament cells. The purpose of the present study was to evaluate the effects of $TGF-{\beta}1$ on the cellular activity of minocycline treated human periodontal ligament cells. Periodontal ligament cells were obtained from the explants of healthy periodontal ligaments of extracted 3rd molars or premolar teeth extracted from the patients for orthodontic treatment. The cells were cultured in minimal essential medium(${\alpha}-MEM$) supplemented with 10.000units/ml penicillin, $10,000{\mu}g/ml$ streptomycin and 10% FBS(fetal bovine serum) at $37^{\circ}C$ in a humidified atmosphere of 5% carbon dioxide and the 5th to the 8th passages of the cells were used. To evaluate the effect of minocycline on cell attachment, the cells were seeded at a cell density of $1.5{\times}10^4$ cells/well in 24-well culture plates and treated with $20{\mu}g/ml$ and $100{\mu}g/ml$ of minocycline for 1.5 h. After trypsinization, the cells were counted with hemocytometer and were taken photographs for observation of cellular morphology. To evaluate the effect of $TGF-{\beta}1$ on minocycline-pretreated periodontal ligament cells, the cells were seeded at a cell density of $1{\times}10^4$ cells/ well in 24-well culture plates and treated with $20{\mu}g/ml$ and $100{\mu}g/ml$ of minocycline for 1.5 h. After incubation, 1 and 10ng/ml of $rh-TGF-{\beta}1$ were also added to the each well and incubated for 1 and 2 days, respectively. Then, MTT assay, DNA synthesis($^3H-thymidine\;assay$), and protein and collagen assay(3H-proline assay) were carried out. In the MIT assay, after 200ul MTT solutionlconeentration of 5mg/ml) were added to the each well of the 24-well plates and incubated for 3 hours, and 200 ul DMSO were added so as to dissolve insoluble blue formazan crystals which was formed in incubated period. Then it read plates on a ELISA reader. For mitogenic assay, 1 uCi/ml $^3H-thymidine$ was added to each well for the final 2 hours of the incubation periods. After labeling, the wells were washed 3 times with ice cold PBS and 4 times with 5% TCA to remove unincorporated label and precipitate the cellular DNA. DNA, with the incorporated $^3H-thymidine$, was solubilized with 500 ul of 0.1% NaOH/0.1% SDS. A 250 ul aliquot was removed from each well and placed in a scintillation vial with 4ml of scintillation cocktail. Using an liguid scintillation counter, counts per minute(CPM) were determined for each samples. 3 uCi/ml $^3H-proline$ was added to each well for the final 4 hours of the incubation periods and total protein and percent collagen synthesis were carried out. The results indicate that minocycline treated group with $100{\mu}g/ml$ concentration for 1.5 hours significantly increased than that of control in cell attachment, and cell process is also evident compared with that of control in cell morphology, and the cellular activity and DNA synthesis rate of cells treated minocycline and $TGF-{\beta}1$ significantly increased than that of control values, but were below to values of the $TGF-{\beta}1$ only treated group in MIT assay and $^3H-thymidine\;assay$, and the total protein synthesis of minocycline and $TGF-{\beta}1$ treated group also significantly increased than that of control values, but the percent collagen synthesis of tested group significantly decreased to compared with control. On the above the findings, the tested group of minocycline and $TGF-{\beta}1$ did not increase the effect on the cell activity than $TGF-{\beta}1$ only tested group and the tested group of minocycline inhibited cell activity. This results indicate that minocycline was effective on cell attachment in early stage, but it is harmful to cell activity, that inhibitory effect of minocycline was compensated with stimulatory effect of $TGF-{\beta}1$.

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Adhesion-induced generation of oxygen free radical from human alveolar macrophages and its mechanisms (폐포대식세포의 부착에 의한 산소유리기 분비능 활성화 및 그 기전)

  • Chung, Man-Pyo;Yoo, Chul-Gyu;Kim, Young-Whan;Han, Sung-Koo;Shim, Young-Soo;Han, Yong-Chol
    • Tuberculosis and Respiratory Diseases
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    • v.43 no.2
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    • pp.210-220
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    • 1996
  • Background : Neutrophils or monocytes separated in vitro by the adherence to plastic surface are known to be activated by surface adherence itself and subsequent experimental data might be altered by surface adherence. In the process of surface adherence, adhesion molecules have a clear role in intracellular signal pathway of cellular activation. Human alveolar macrophages(HAM) are frequently purified by the adherence procedure after bronchoalveolar lavage. But the experimental data of many reports about alveolar macrophages have ignored the possibility of adhesion-induced cellular activation. Method : Bronchoalveolar lavage was performed in the person whose lung of either side was confirmed to be normal by chest CT. With the measurement of hydrogen peroxide release from adherent HAM to plastic surface and non-adherent HAM with or without additional stimulation of phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine (fMLP), we observed the effect of the adherence to plastic surface. We also evaluated the effect of various biological surfaces on adhesion-induced activation of HAM. Then, to define the intracellular pathway of signal transduction, pretreatment with cycloheximide, pertussis toxin and anti-CD11/CD18 monoclonal antibody was done and we measured hydrogen peroxide in the culture supernatant of HAM. Results : 1) The adherence itself to plastic surface directly stimulated hydrogen peroxide release from human alveolar macrophages and chemical stimuli such as phorbol myristate acetate(PMA) or N-formyl-methionyl-leucyl-phenylalanine(fMLP) colud not increase hydrogen peroxide release in these adherent macrophages which is already activated. 2) PMA activated human alveolar macrophages irrespective of the state of adhesion. However, fMLP stimulated the release of hydrogen peroxide from the adherent macrophages, but not from the non-adherent macrophages. 3) HAM adherent to A549 cell(type II alveolar epithelium-like human cell line) monolayer released more hydrogen peroxide in response to both PMA and fMLP. This adherence-dependent effect of fMLP was blocked by pretreatment of macrophages with cycloheximide, pertussis toxin and anti-CD18 monoclonal antibody, Conclusion : These results suggest that the stimulatory effect of PMA and fMLP can not be found in adherent macrophage because of the activation of human alveolar macrophage by the adherence to plastic surface and the cells adhered to biologic surface such as alveolar epithelial cells are appropriately responsive to these stimuli. It is also likely that the effect of fMLP on the adherent macrophage requires new protein synthesis via G protein pathway and is dependent on the adhesion between alveolar macrophages and alveolar epithelial cells by virtue of CD11/CD18 adhesion molecules.

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Effects of Pesticides on Soil Microflora -III. Effects of Pesticides on Microorganisms Related to the Nitrogen Cycle in the Submerged Soil (농약(農藥)이 토양미생물상(土壤微生物相)에 미치는 영향(影響)에 관(關)한 연구(硏究) -III. 농약(農藥)이 담수토양(湛水土壤)의 질소순환(窒素循環)에 관여(關與)하는 미생물(微生物)에 미치는 영향(影響))

  • Lee, Kyung-Bo;Kim, Yong-Woong;Kim, Kwang-Sik
    • Korean Journal of Soil Science and Fertilizer
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    • v.21 no.2
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    • pp.149-159
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    • 1988
  • This study was made to investigate the effect of pesticides on microflora to nitrogen metabolism, nitrification and nitrogen fixing activity in the submerged soil. The results are summarized as follows; Pesticides treatment leaded to the inhibition of $NH_4{^-}$-oxdizers, $NO_3{^-}$-reducer, and denitrifying bacteria population. $NO_2{^-}$-oxdizers were inhibited by cabamate compounds, carbofuran and MIPC. Simetryne seemed to stimulate the denitrifying bacteria at 60 days after incubation. Generally, formation of $NO_2{^-}$ and $NO_3{^-}$ tended to decrease by pesticides application. Pesticides application stimulated Azotobacter and Clostridia populations, while simetryne inhibited Athiorhodaceae and Thiorhodaceae. However acephate seemed to be stimulatory to blue-geen algae. $C_2H_2$-reducing activity by acephate was clearly appeared. The change of $C_2H_2$-reducing activity did not seems to be affected by pesticides application.

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Bioequivalence of Tofim Tablet to Grandaxin Tablet (Tofisopam 50 mg) (그란닥신 정(토피소팜 50 mg)에 대한 토핌 정의 생물학적 동등성)

  • Cho, Hea-Young;Jeong, Hyun-Cheol;Her, Su-Hi;Lim, Dong-Gu;Moon, Jai-Dong;Lee, Yong-Bok
    • Journal of Pharmaceutical Investigation
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    • v.31 no.2
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    • pp.131-136
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    • 2001
  • Tofisopam is a new type of tranquilizer valuable for the relief of anxiety and tension in a wide range of emotional disorders. Tofisopam has the therapeutic characteristics of a minor tranquilzer and a mild stimulatory effect. The purpose of the present study was to evaluate the bioequivalence of two tofisopam tablets, $Grandaxin^{TM}$ (Hwan In Pharmaceutical Co., Ltd.) and $Tofim^{TM}$ (Kyung Dong Pharmaceutical Co., Ltd.), according to the guidelines of Korea Food and Drug Administration (KFDA). Eighteen normal male volunteers, $23.11\;{\pm}\;2.83$ years in age and $65.43\;{\pm}\;7.64\;kg$ in body weight, were divided into two groups and a randomized $2{\times}2$ cross-over study was employed. After one tablet containing 50 mg of tofisopam was orally administered, blood was taken at predetermined time intervals and the concentrations of tofisopam in serum were determined using HPLC method with UV detector. The pharmacokinetic parameters such as $AUC_t$, $C_{max}\;and\;T_{max}$ were calculated and ANOVA test was utilized for the statistical analysis of the parameters. The results showed that the differences in $AUC_t$, C_{max}\;and\;T_{max}$ between two tablets based on the $Grandaxin^{TM}$ were -5.59%, 2.22% and -13.18%, respectively. Minimum detectable differences $({\Delta})$ at ${\alpha}=0.10$ and $1-{\beta}=0.8$ were less than 20% (e.g., 14.95% and 19.34% for $AUC_t\;and\;C_{max}$, respectively). The powers $(1-{\beta})$ at ${\alpha}=0.10$, ${\Delta}=0.2$ for $AUC_t$ and $C_{max}$ were 95.21% and 81.93%, respectively. The 90% confidence intervals were within {\pm}20%$ (e.g., $-15.64{\sim}4.45$ and $-10.77{\sim}15.21$ for $AUC_t\;and\;C_{max}$, respectively). Two parameters met the criteria of KFDA for bioequivalence, indicating that $Tofim^{TM}$ tablet is bioequivalent to $Grandaxin^{TM}$ tablet.

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Effects of Leucine on in Vivo Protein Synthesis in Skeletal Muscles of Fed and Food-Deprived Rats (Leucine이 정상 또는 굶게 된 쥐의 골격근육의 단백질 생합성에 미치는 영향)

  • 장순옥
    • Journal of Nutrition and Health
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    • v.21 no.4
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    • pp.242-252
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    • 1988
  • In vivo effects of leucine on skeletal muscle protein synthesis in fed and I-day food deprived young rats were examined. Animals assigned to leucine group were given a single i.p. injection of 80 or 160flmoles of leucine while control group animals were saline sham injected. The rate of protein synthesis was measured by the amount of $^{14}\textrm{C} incorporated into muscle protein after a single injection of $^{14}\textrm{C}-tyrosine, IO$\mu$ Ci/l00g B.W. Examined muscles were two different types of hind limb muscles. the oxidative solues and the glycolytic EDL and plantaris. Administered leucine elevated the concentration of free leucine in soleus muscles by 4-6.8 times the normal level. A massive dose of leucine, 160 flmoles, stimulated protein synthesis in the EDL and plantaris by 24 %, 29 % respectively of straved rats. The soleus of I-day food deprived rats and both types of muscles in fed rats did not respond to the injected leucine. The synthesis rate of the EDL and plantaris was supressed to one-half of the normal while the soleus that was not stimulated by leucine maintained a relatively normal rate, 78 %, of protein synthesis after I-day of food deprivation. Thus, in vivo stimulatory effect of leucine appears to be not a general phenomenon but to be related to the degree of catabolic condition developed by stress such as food deprivation. Although anabolic effects of leucine observed in this study was limited, any applicability of this special property of leucine to human subjects for the purpose of protein sparing in skeletal muscles remains to be examined.

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Activation Mechanism of Arachidonic Acid in Human Neutrophil Function (사람 중성호성 백혈구의 기능에 있어서 Arachidonic Acid의 활성화 기전)

  • Sim, Jae-Kun;Lee, Chung-Soo;Shin, Yong-Kyoo;Lee, Kwang-Soo
    • The Korean Journal of Pharmacology
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    • v.28 no.1
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    • pp.91-102
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    • 1992
  • In $Ca^{++}$ containing media, arachidonic acid markedly stimulated superoxide and $H_2O_2$ generation and activated NADPH oxidase. In $Ca^{++}$ free media, stimulatory action of arachidonic acid on NADPH oxidase was not detected. Arachidonic acid-stimulated respiratory burst was inhibited by EGTA, TMB-8, verapamil, diltiazem, nifedipine, dibucaine, lidocaine, CCCP, 2,4-dinitrophenol, sodium arsenate, chlorpromazine, theophylline, $HgCl_2$, PCMB and PCMBSA but not affected by tetrodotoxin, tetraethylammonium chloride and procaine. EGTA almost completely inhibited release of ${\beta}-glucuronidase$ by arachidonic acid and verapamil, CCCP and theophylline slightly inhibited it, whereas dibucaine did not show any significant effect. Arachidonic acid induced $Ca^{++}$ release from intact neutrophils and it was decreased by TMB-8. Arachidonic acid-induced elevation of intracellular free $Ca^{++}$ level was inhibited by EGTA and CCCP and slightly inhibited by TMB-8. Amount of intracellular free $Ca^{++}$ increased by either arachidonic acid plus verapamil or arachidonic acid plus dibucaine was greater than that by arachidonic acid alone. These results suggest that various changes of biochemical events may be implicated in the functional expression in neutrophils activated by arachidonic acid. Arachidonic acid appears to elevate cytosolic free $Ca^{++}$ level by stimulating $Ca^{++}$ release from intracellular $Ca^{++}$ storage sites. During activation of neutrophils, $Ca^{++}$ influx and efflux may be accomplished, simultaneously.

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Ashitaba and red ginseng complex stimulates exercise capacity by increasing mitochondrial biogenesis (미토콘드리아 생합성 촉진을 통한 신선초와 홍삼 복합물의 운동수행능력 증가 효과)

  • Kim, Changhee;Kim, Mi-Bo;Lee, Seung-Ho;Kim, Ye-Jin;Hwang, Jae-Kwan
    • Korean Journal of Food Science and Technology
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    • v.49 no.6
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    • pp.685-692
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    • 2017
  • Mitochondrial biogenesis-a process that leads to an increment in the number and density of mitochondria, improves physical performance and body health by enhancing exercise capacity. In the present study, we investigated the stimulatory effect of Ashitaba and red ginseng complex (ARC) on exercise capacity in L6 skeletal muscle cells and mice. In L6 skeletal muscle cells, ARC increased the mitochondrial contents and ATP production by activating AMP-activated protein kinase (AMPK), sirtuin 1 (SIRT1), and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-$1{\alpha}$) and up-regulating the mRNA expression of nuclear respiratory factor-1 (NRF-1) and mitochondrial transcription factor A (TFAM). In the animal experiments, mice treated with ARC showed an increment in exercise capacity as compared with mice treated with Ashitaba extract or red ginseng extract alone. These studies indicate that ARC might serve as a potential natural candidate for enhancing exercise capacity by stimulation of mitochondrial biogenesis.