• Title/Summary/Keyword: p-AMPK

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Effects of Essential Oils Extracted from Cnidii Rhizoma on Differentiation and Adipogenesis in 3T3-L1 Adiopocytes (천궁(川芎)의 정유 추출물이 3T3-L1 세포의 분화 및 지방 생성에 미치는 영향)

  • Choi, Soo-Min;Kim, So-Young;Park, Na-Ri;Kim, Jung-Min;Yang, Doo-Hwa;Woo, Chang-Hoon;Kim, Mi-Ryeo;An, Hee-Duk
    • Journal of Korean Medicine Rehabilitation
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    • v.28 no.3
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    • pp.13-25
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    • 2018
  • Objectives We investigated anti-obesity effects of essential oils extracted from Cnidii Rhizoma (CR) in immature adipocytes to magnify it's clinical therapeutic usage. Methods Essential oil of CR was extracted with ethyl acetate or petroleum ether and through steam distillation, respectively. Oil red-O staining for monitoring its inhibition effect on adipogenesis and differentiation in murine 3T3-L1 adipocytes and 3-(4,5-methylthiazol-2-yl)-2,5-diphenyletetra zolium bromide (MTT) assay for cell safety were done. Also phospho-adenosine monophosphate (AMP)-activted protein kinase (P-AMPK), AMP-activated protein kinase, phospho-acetyl-CoA carboxylase (P-ACC), acetyl-CoA carboxylase, peroxisome proliferator-activated receptor-${\alpha}$ (PPAR-${\alpha}$), peroxisome proliferator-activated receptor-${\gamma}$ (PPAR-${\gamma}$) and CCAAT/enhancer binding protein ${\alpha}$ (C/EBP-${\alpha}$) expressions as obesity-related factors were measured by western blot analysis. Results Protein expressions of P-AMPK, P-ACC and PPAR-${\alpha}$ were increased in essential oils-treated adipocytes compared to those of control group, respectively. Furthermore, protein expressions of PPAR-${\gamma}$ and C/EBP-${\alpha}$ were decreased in essential oils-treated adipocytes compared to those of control group, respectively. Conclusions These results demonstrate that essential oils of CR inhibit adipogenesis and differentiation. Also they promote the oxidation of fatty acids in adipocytes. Thus, results suggest that essential oils of CR could be used as a valuable material for anti-obesity therapeutics via control of lipid metabolism.

Effects of steamed Polygonatum odoratum extract on inhibition of adipocyte differentiation and lowing lipid in 3T3-L1 adipocytes (증자 둥굴레 추출물의 3T3-L1 지방세포에서 분화억제 및 지질강하 효과)

  • Kang, Byung Tae;Choe, Won Kyung;Park, Dong Cheol;Kim, Jong Kuk;Park, Mora;Kim, Sung Ok;Kim, Mi Ryeo
    • The Korea Journal of Herbology
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    • v.29 no.2
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    • pp.15-21
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    • 2014
  • Objectives : The purpose of this study was to investigate inhibitory effects of steamed Polygonatum odoratum extract (POE) on differentiation and adipogenesis in 3T3-L1 adipocytes. Methods : Polygonatum odoratum (P. odoratum) extract was extracted with ethyl acetate. Total phenolic and flavonoid contents in POE were measured for antioxidant activity. The spectrophotometric method was used to determine the DPPH and ABTS radical scavenging activity and ferric-reducing antioxidant potential (FRAP). MTT assay was examined for cell toxicity, oil red O staining was performed for intracelluar adipogenesis in differentiated 3T3-L1 adipocytes. Western blot analysis for measurement of CCAAT/enhancer-binding protein ${\alpha}$ ($C/EBP{\alpha}$), peroxisome proliferator-activated receptor${\gamma}$ ($PPAR{\gamma}$) and AMP-activated protein kinase (AMPK) expressions were performed. Results : The results revealed that POE has antioxidant activities. Contents of total polyphenolics and flavonoids were $50.83{\pm}1.52$ GAE mg/100g dry weight of POE and $17.05{\pm}2.47$ RE mg/100g dry weight of POE, respectively. DPPH radical scavenging activity, and FRAP in 10 mg/ml concentration were $92.1{\pm}0.6%$, $244.8{\pm}9.0{\mu}M$ Fe(II) and ABTS inhibition in 5 mg/ml concentration was $84.8{\pm}4.1%$. Treatment of POE in adipocytes inhibited the differentiation and adipogenesis of 3T3-L1 adipocytes compared to those of vehicle control. Additionally, protein expressions of $C/EBP{\alpha}$ and $PPAR{\gamma}$, major transcription factor for the adipogenic genes, were significantly decreased compared to those of vehicle control (p<0.05). Futhermore, phosphorylation of AMPK was increased in 3T3-L1 adipocytes treated with POE compared to that of vehicle control (p<0.05). Conclusions : we demonstrate that steamed P. odoratum extract (POE) has potentiating antioxidant activities, inhibits differentiation and lipid accumulation and also induces energy expenditure in adipocytes, which may contribute to antiobesity property.

Pharmacological Analyses of HIMH0021 Extracted from Acer Tegmentosum and Efficacy Tests of Steatohepatitis and Hepatic Fibrosis in NASH/ASH (산겨릅나무로부터 추출된 HIMH0021의 알콜성·비알콜성 지방간염 질환에서의 약리학적 분석 및 지방간염 및 간섬유화 억제능 평가)

  • Ji Hoon Yu;Yongjun Lee
    • Proceedings of the Plant Resources Society of Korea Conference
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    • 2021.04a
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    • pp.5-5
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    • 2021
  • Alcoholic and nonalcoholic steaohepatitis is a leading form of chronic liver disease with few biomakers ad treatment options currently available. a progressive disease of NAFLD may lead to fibrosis, cirrhosis, and hepatocellular carcinoma. Recently, we extracted HIMH0021, which is an active flavonoid component in the Acer tegmentosum extract, has been shown to protect against liver damage caused by hepatic dysfunction. Therefore, in this study, we aimed to investigate whether HIMH0021 could regulate steatohepatitis and liver fibrosis during alcoholic or nonalcoholic metabolic process. HIMH0021, which was isolated from the active methanol extract of A. tegmentosum, inhibited alcohol-induced steatosis and attenuated the serum levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) during hepatocellular alcohol metabolism, both of which promote lipogenesis as well as liver inflammation. Treatment with HIMH0021 conferred protection against lipogenesis and liver injury, inhibited the expression of cytochrome P4502E1, and increased serum adiponectin levels in the mice subjected to chronic-plus-binge feeding. Furthermore, in hepatocytes, HIMH0021 activated fatty acid oxidation by activating pAMPK, which comprises pACC and CPT1a. These findings suggested that HIMH0021 could be used to target a TNFα-related pathway for treating patients with alcoholic hepatitis.

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Anti-Diabetic Effect of Sericultural Product in High Fat Diet-Fed Mice (고지방식이급여 마우스에서 잠상산물의 항당뇨 효능)

  • Ahn, Eunyeong;Choi, Sang-Won;Kim, Eunjung
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.3
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    • pp.289-297
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    • 2017
  • The objective of this study was to identify and compare the anti-diabetic effects of mulberry leave (ML), silkworm (SK), mulberry fruit (MF), and Cudrania tricuspidata BUREAU (CT) extracts in high fat diet (HFD)-induced obese and diabetic mice. C57BL/6N mice were assigned to six groups: normal diet (ND, n=7), HFD (n=10), HFD with 5% ML powder (ML, n=10), HFD with 2% SK powder (SK, n=10), HFD with 5% MF powder (MF, n=10), and HFD with 5% CT powder (CT, n=10). Mice were fed their assigned diet for 14 weeks. ML group showed significant reduction in levels of plasma glucose and insulin compared with the HFD group. Plasma total cholesterol (T-C) was significantly reduced by ML and SK compared with the HFD group. Plasma high-density lipoprotein cholesterol (HDL-C) and HTR (HDL-C to T-C ratio) levels of the ML, SK, MF, and CT groups were significantly elevated compared to the HFD group. Moreover, concentrations of hepatic T-C and triglycerides in the ML, SK, MF, and CT groups were significantly reduced in comparison to the HFD group. Levels of pAKT, pS6K, and pAMPK significantly increased in the ML group compared with the HFD group. Taken together, ML appears to be the most potent anti-diabetic and anti-dyslipidemic substance among sericultural products. ML could be developed as a potential agent for diabetes and its complication management.

Effects of Acanthopanax senticosus Water Extract on Glucose-Regulating Mechanisms in HepG2 Cells (가시오갈피 물 추출물이 간세포에서 포도당 이용 대사에 미치는 영향)

  • Kim, Dae-Jung;Kang, Yun Hwan;Kim, Kyoung Kon;Kim, Tae Woo;Park, Jae Bong;Choe, Myeon
    • Journal of the Korean Society of Food Science and Nutrition
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    • v.46 no.5
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    • pp.552-561
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    • 2017
  • This study aimed to investigate glucose uptake mechanisms and metabolic mechanisms for absorbed glucose in HepG2 cells treated with Acanthopanax senticosus water extract (ASW). A colorimetric assay kit was used to measure polyphenol content, glucokinase (GK) activity, glucose uptake, glucose consumption in cell culture medium, and glycogen content. RT-PCR and western blotting were performed to examine changes in the expression levels of glucose transporter 2 (GLUT2), hepatocyte nuclear factor $1{\alpha}$ ($HNF-1{\alpha}$), phosphatidylinositol 3-kinase (PI3k), protein kinase B (Akt), phospho-AMP-activated protein kinase (AMPK), phosphoenolpyruvate carboxykinase, GK, and glycogen synthase kinase $3{\beta}$ ($GSK3{\beta}$). Increased glucose uptake upon ASW treatment was confirmed to result from increased expression of $HNF-1{\alpha}$, which is one of the transcription factors acting on the GLUT2 promoter. From the measurements of GK activity, we observed that ASW had an effect on glucose phosphorylation, and we also confirmed that increased AMPK phosphorylation promoted glycolysis and suppressed gluconeogenesis. We confirmed that the increase in glycogen upon ASW treatment was induced by activation of Akt by PI3k, followed by phosphorylation of $GSK3{\beta}$. This study demonstrates that ASW activates glucose metabolic mechanisms in liver cells and is therefore a potential candidate to alleviate diabetes.

Inhibitory Effects of Rubus crataegifolius Leaf Water Extract on Adipocyte Differentiation and Adipogenesis in 3T3-L1 Preadipocytes

  • Mee-Kyung Kim
    • Journal of the Korea Society of Computer and Information
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    • v.29 no.1
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    • pp.187-194
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    • 2024
  • In this study, we examined the effects of Rubus crataegifolius leaf on the inhibition of differentiation and adipogenesis of 3T3-L1 preadipocytes to confirm their potential for use as an anti-obesity functional material. Rubus crataegifolius leaves water extracted using hot water were then concentrated for use, with an extract yield of 4.76%. The result of measuring the rate of 3T3-L1 cell survival of Rubus crataegifolius leaf extract (RCLE) showed growth inhibition of 13% at a concentration of 1,000 ㎍/mL. Thus, in this study, experiments were performed using RCLE treatment concentrations up to 500 ㎍/mL. Production of triglycedie in 3T3-L1 cells showed a dose-dependent decrease, and the rate of reduction was 28.7, 40.8, and 51.6% at concentrations of 100, 300, and 500 ㎍/mL, respectively, compared to the control group. In addition, the results confirmed that suppression of lipogenesis was achieved by suppressing the expression of peroxisome proliferator-activated receptor γ (PPAR γ), CCAAT/enhancer-binding protein α (C/EBP α), sterol regulatory element-binding protein-1c (SREBP-1c), fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), and increasing the expression of p-activated protein kinase (p-AMPK). Based on these results, it is believed that Rubus crataegifolius leaf extract can be used in the effort to manage obesity by regulating factors related to adipocyte differentiation and adipogenesis.

Convergence study on the through inhibition of differentiation in 3T3-L1 cells of ethanol extract from Trichosanthes kirilowii Maxim. Root (하늘타리(Trichosanthes kirilowii Maxim.) 뿌리 에탄올 추출물의 3T3-L1 지방세포 분화 억제 융합연구)

  • Kim, Sung Ok;Jeung, Ji-Suk
    • Journal of the Korea Convergence Society
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    • v.10 no.3
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    • pp.127-133
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    • 2019
  • The ami of our study was on the anti-obesity effect of ethanol extract from Trichosanthes kirilowii Maxim root (TKM) in murine adipocytes, 3T3-L1 cells. This study focused on anti-adipogenic activity through inhibition of cell differentiation in 3T3-L1 cells treated TKM. 100 ug/ml of non-cytotoxic TEM remarkablely inhibited content of triglycerol and suppressed expressions of $C/EBP{\alpha}$, $PPAR{\gamma}a$ and SREBP-1c related with lipogenic transcription factors in theres 3T3-L1 cells compared to (-)control cells. As phosphorylations of AMPK and ACC were incerased, HSL and CPT-1 mRNA expression increased upon TKM treatment, which involved in inhibition of fatty acid synthase expression. In conclusion, these results indicate that TKM can inhibit mRNA and protein expression of lipogenic genes in 3T3-L1 adipocytes. Our study suggests that TKM has potential anti-obesity effects and is a convergence therapeutic functional agent with anti-adipogenic activity via hypolipogenesis.

The Anti-adipogenic and Lipolytic Effect of Jinkyool (Citrus sunki Hort. ex Tanaka) Leaf Extract in 3T3-L1 Cells (3T3-L1 지방세포에서 진귤 잎 유래 polymethoxyflavones 다량 함유 분획물(PRF)의 항지방생성 및 지방분해 효과)

  • Jin, Yeong Jun;Jang, Mi Gyeong;Kim, Jae-Won;Kang, Minyeong;Ko, Hee Chul;Kim, Se Jae
    • Journal of Life Science
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    • v.32 no.7
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    • pp.542-549
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    • 2022
  • Polymethoxyflavones (PMFs) are flavonoids mainly found in citrus fruits and have been reported to exhibit a wide range of bioactivities, including anti-obesity, anti-cancer, and anti-inflammatory actions. To utilize PMFs as functional materials, it is necessary to develop a simple method of obtaining PMFs from citrus tissues containing a large amount of PMFs. It has been reported that Jinkyool (C. sunki Hort ex. Tanaka) peel contained a large amount of PMFs, but there are no studies on PMFs isolated from its leaves. In this study, we established a simple procedure for obtaining the PMF-rich fraction (PRF) from the leaves of Jinkyool and investigated the effects of PRF on lipid metabolism in 3T3-L1 cells. PRF inhibited lipogenesis during the differentiation of 3T3-L1 preadipocytes. It decreased the expression of peroxisome proliferator-activated receptor gamma (PPAR𝛾) and CCAAT/enhancer binding protein alpha (CEBP𝛼), FAS, and adipocyte fatty-acid-binding protein 2 (aP2). In mature 3T3-L1 adipocytes, PRF increases the phosphorylation of protein kinase A (PKA)/hormone-sensitive lipase (HSL), which are key factors involved in lipolysis. Moreover, it increases the phosphorylation of the AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) involved in fatty acid oxidation. These results suggest that PRF from Jinkyool leaves can be used as an anti-obesity agent with the action of inhibiting lipogenesis and promoting lipolysis and fatty acid oxidation in 3T3-L1 adipocytes.

Water Extract of Fermented New Korean Medicinal Mixture (F-MAPC) Controls Intracellula Adipogenesis and Glut-4 dependent Glucose Uptake in 3T3-L1 Adipocytes and L6 Myoblasts (세포 내 지방생성과 Glut-4 의존성 포도당 운반에 미치는 발효복합한약 물추출물(F-MAPC)의 영향)

  • Jeon, Seo Young;Park, Ji Young;Kim, Sung Ok;Lee, Eun Sil;Koo, Jin Suk;Kim, Mi Ryeo
    • The Korea Journal of Herbology
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    • v.29 no.1
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    • pp.45-52
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    • 2014
  • Objectives : The aim of this study was to investigate the effects water extract of fermented new korean medicinal mixture, combinations of Mori Folium, Adenophorae Radix, Phllostachyos Folium and Citri Pericarpium (F-MAPC), on adipocyte differentiation, adipogenesis and glucose uptake using undiffernentiated 3T3-L1 adipocytes and L6 myoblasts. Methods : Each herb and those mixture were respectively fermented and then extracted with water. We carried on MTT assay for check-up on cell toxicity, Oil Red O staining for determination of cell differentiation and intracelluar adipogenesis. Western blot analysis for measurement of pAMPK and pACC, $C/EBP{\alpha}$, $PPAR{\gamma}$ and Glut-4 protein expressions were performed. Results : F-MAPC showed significant inhibitory activity on adipocyte differentiation in 3T3-L1 preadipocytes without affecting cell toxicity as assessed by measuring fat accumulation, and this effect was 2 fold higher in 0.2 mg/ml F-MAPC than that of the same dose of each fermented herbal extract alone. In addition, these effects were associated with modulation of adipogenic transcription factors, such as $C/EBP{\alpha}$, $PPAR{\gamma}$, as well as stimulated phosphorylations of AMPK and ACC. Translocation of Glut-4 was significantly increased by 10.2% in L6 cells treated with 0.2 mg/ml F-MAPC compared with that of control. Conclusions : These results demonstrate that F-MAPC may be an ideal candidate for therapy of obesity and diabetes by disturbing the differentiation into adipocytes, as well as the inducement of intramuscular glucose uptake from blood.

α, γ-Mangostins Induce Autophagy and Show Synergistic Effect with Gemcitabine in Pancreatic Cancer Cell Lines

  • Kim, Myoungjae;Chin, Young-Won;Lee, Eun Joo
    • Biomolecules & Therapeutics
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    • v.25 no.6
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    • pp.609-617
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    • 2017
  • Pancreatic cancer is one of the most lethal and aggressive cancers in the world. However, no effective treatment is currently available for pancreatic cancer. The objective of this study was to determine the anti-pancreatic cancer effect of ${\alpha}$-mangostin (${\alpha}M$) and ${\gamma}$-mangostin (${\gamma}M$) extracted from the pericarp of Garcinia mangostana L.. Both ${\alpha}$M and ${\gamma}M$ reduced the viability of pancreatic cancer cells MIA PaCa-2 and PANC-1 in a dose-dependent manner. These compounds induced apoptosis by increasing c-PARP and c-Caspase 3 levels. They also induced autophagy by increasing levels of microtubule-associated protein 1A/1B light chain 3B (LC3II) in both cell lines while decreasing sequestosome 1 (p62) in MIA PaCa-2. Both ${\alpha}$M and ${\gamma}M$ induced autophagy through increasing phosphorylation levels of AMP-activated protein kinase (p-AMPK) and p38-mitogen activated protein kinase (p-p38) while decreasing phosphorylation level of mammalian target of rapamycin complex 1 (p-mTOR). Of various microRNAs (miRNA), miR-18a was found to be a putative regulatory miRNA for autophagy induced by ${\alpha}$M or ${\gamma}M$. In combination with gemcitabine, a compound frequently used in pancreatic cancer treatment, ${\alpha}$M and ${\gamma}M$ showed synergistic anti-cancer effects in MIA PaCa-2. Collectively, these results suggest that ${\alpha}$M and ${\gamma}M$ can induce apoptosis and autophagy in pancreatic cancer cells and that their anti-cancer effect is likely to be associated with miR-18a. In conclusion, ${\alpha}$M and ${\gamma}M$ might be used as a potential new therapy for pancreatic cancer.