AMPK

Protein kinase, AMP-activated, alpha-2 catalytic subunit

1p32.2


Naturopathic Agents Known to Influence Entity Expression:
  • Scutellaria baicelensis
  • Gynostemma pentaphyllum
  • Ephedra herb
  • Green Tea, Kukicha, Bancha
  • Coptis rhizome
  • Wogonin
  • Epigallocatechin 3-gallate
  • Salix alba (willow)
  • Rheum palmatum
  • Green Tea Polyphenol Extract
  • Skullcap (Scutellaria baicalensis)
  • Laminaria japonica
  • Co-enzyme Q10
  • Bupleurum root


    

PHARMACEUTICAL BIOLOGY 2012 APR; 50 (4): 506-15.


The herbal composition GGEx18 from Laminaria japonica, Rheum palmatum, and Ephedra sinica reduces obesity via skeletal muscle AMPK and PPARα.


Shin SS, Park D, Lee HY, Hong Y, Choi J, Oh J, Lee H, Lee HR, Kim MR, Shen ZB, Cui HH, Yoon M,





Since AMP-activated protein kinase (AMPK) activation in skeletal muscle of obese rodents stimulates fatty acid oxidation, it is reasonable to hypothesize that pharmacological activation of AMPK might be of therapeutic benefit in obesity.

To investigate the effects of the traditional Korean anti-obesity drug GGEx18, a mixture of three herbs, Laminaria japonica Aresch (Laminariaceae), Rheum palmatum L. (Polygonaceae), and Ephedra sinica Stapf (Ephedraceae), on obesity and the involvement of AMPK in this process.

After high fat diet-induced obese mice were treated with GGEx18, we studied the effects of GGEx18 on body weight, fat mass, skeletal muscle lipid accumulation, and the expressions of AMPK, peroxisome proliferator-activated receptor ά (PPARα), and PPARα target genes. The effects of GGEx18 and/or the AMPK inhibitor compound C on lipid accumulation and expression of the above genes were measured in C2C12 skeletal muscle cells.

Administration of GGEx18 to obese mice for 9 weeks significantly (p < 0.05) decreased body and adipose tissue weights compared with obese control mice (p < 0.05). Lipid accumulation in skeletal muscle was inhibited by GGEx18. GGEx18 significantly (p < 0.05) increased skeletal muscle mRNA levels of AMPKα1 and AMPKα2 as well as PPARα and its target genes. Consistent with the in vivo data, GGEx18 inhibited lipid accumulation, and similar activation of genes was observed in GGEx18-treated C2C12 cells. However, compound C inhibited these effects in C2C12 cells.

These results suggest that GGEx18 improves obesity through skeletal muscle AMPK and AMPK-stimulated expression of PPARα and its target enzymes for fatty acid oxidation.





PubMed ID: 22129093



    

BIOORGANIC & MEDICINAL CHEMISTRY 2011 NOV; 19 (21): 6254-60.


New dammarane-type glucosides as potential activators of AMP-activated protein kinase (AMPK) from Gynostemma pentaphyllum.


Nguyen PH, Gauhar R, Hwang SL, Dao TT, Park DC, Kim JE, Song H, Huh TL, Oh WK,



AMP-activated protein kinase (AMPK) is a key sensor and regulator of glucose, lipid, and energy metabolism throughout the body. Activation of AMPK improves metabolic abnormalities associated with metabolic diseases including obesity and type-2 diabetes. The oriental traditional medicinal herbal plant, Gynostemma pentaphyllum, has shown a wide range of beneficial effects on glucose and lipid metabolism. In this study, we found that G. pentaphyllum contains two novel dammarane-type saponins designated as damulin A (1), 2α,3β,12β-trihydroxydammar-20(22)-E,24-diene-3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside], and damulin B (2), 2α,3β,12β-trihydroxydammar-20,24-diene-3-O-[β-D-glucopyranosyl-(1→2)-β-D-glucopyranoside], that strongly activate AMPK in cultured L6 myotube cells. Damulins A and B also increased β-oxidation and glucose uptake with increasing GluT4 translocation to the plasma membrane in L6 myotube cells. Taken together our results indicate that activation of AMPK by damulins A and B may contribute to beneficial effect of G. pentaphyllum on glucose and lipid metabolism.



PubMed ID: 21978948



    

THE AMERICAN JOURNAL OF CHINESE MEDICINE 2011 ; 39 (1): 53-63.


Anti-diabetic effects of a Coptis chinensis containing new traditional Chinese medicine formula in type 2 diabetic rats.


Zhen Z, Chang B, Li M, Lian FM, Chen L, Dong L, Wang J, Yu B, Liu WK, Li XY, Qin PJ, Zhang JH, Tong XL,



The Chinese formula Tang-Min-Ling (TML), an improved product of the decoction of Dachaihu which has a history of more than 2000 years, has main constituents of Coptis chinensis Franch, Scutellaria baicalensis Georgi, Rheum officinale Baill and Bupleurum chinense DC. A multi-central randomized controlled investigation performed previously by us has showed that TML has positive effects on regulating glycometabolism in type 2 diabetes (T2DM) patients, but the mechanisms remain unclear. Using Otsuka Long-Evans Tokushima Fatty (OLETF) rats as an animal model with rosiglitazone as a positive control, we were able to detect TML's effect on the serum glucose, serum lipid, serum leptin and adiponcetin after oral administration for 12 weeks. We were also able to detect the insulin resistance level by a glucose clamp test and study the mechanisms of TML in improving insulin resistance by detecting skeletal muscle AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4). Results showed that TML significantly reduced the glucose area under a curve of the oral glucose tolerance test, and had a positive effect in regulating serum lipid metabolism. TML treatment also significantly reduced the serum leptin level, but it had no effect on the serum adiponectin level. The AMPK enzymatic activity and GLUT4 expression in Skeletal Muscle were also upregulated in the TML group. The results suggest that the Chinese medicine TML, which contains Coptis chinensis Franch as one of its components, improves glycometabolism and its possible mechanisms may involve in improvement of insulin resistance of OLETF rats.



PubMed ID: 21213398



    

MOLECULAR NUTRITION & FOOD RESEARCH 2011 SEP; 55 SUPPL 2 (1): S227-40.


Coenzyme Q10 suppresses oxLDL-induced endothelial oxidative injuries by the modulation of LOX-1-mediated ROS generation via the AMPK/PKC/NADPH oxidase signaling pathway.


Tsai KL, Chen LH, Chiou SH, Chiou GY, Chen YC, Chou HY, Chen LK, Chen HY, Chiu TH, Tsai CS, Ou HC, Kao CL,



The Chinese formula Tang-Min-Ling (TML), an improved product of the decoction of Dachaihu which has a history of more than 2000 years, has main constituents of Coptis chinensis Franch, Scutellaria baicalensis Georgi, Rheum officinale Baill and Bupleurum chinense DC. A multi-central randomized controlled investigation performed previously by us has showed that TML has positive effects on regulating glycometabolism in type 2 diabetes (T2DM) patients, but the mechanisms remain unclear. Using Otsuka Long-Evans Tokushima Fatty (OLETF) rats as an animal model with rosiglitazone as a positive control, we were able to detect TML's effect on the serum glucose, serum lipid, serum leptin and adiponcetin after oral administration for 12 weeks. We were also able to detect the insulin resistance level by a glucose clamp test and study the mechanisms of TML in improving insulin resistance by detecting skeletal muscle AMP-activated protein kinase (AMPK) and glucose transporter 4 (GLUT4). Results showed that TML significantly reduced the glucose area under a curve of the oral glucose tolerance test, and had a positive effect in regulating serum lipid metabolism. TML treatment also significantly reduced the serum leptin level, but it had no effect on the serum adiponectin level. The AMPK enzymatic activity and GLUT4 expression in Skeletal Muscle were also upregulated in the TML group. The results suggest that the Chinese medicine TML, which contains Coptis chinensis Franch as one of its components, improves glycometabolism and its possible mechanisms may involve in improvement of insulin resistance of OLETF rats.

The lectin-like oxidized low-density lipoprotein receptor (LOX-1) is one pivot receptor for oxidized low-density lipoprotein (oxLDL) in human endothelial cells. Co-enzyme Q10 (Co Q10) has been widely used in clinical intervention. However, the molecular mechanisms underlying its protective effects against oxidative stress in endothelial cells are still largely unknown. This study was designed to test the hypothesis that Co Q10 mitigates oxLDL-induced endothelial oxidative injuries via modulation of LOX-1-mediated reactive oxygen species (ROS) generation and explored the role of AMP-activated protein kinase (AMPK), a negative regulator of NADPH oxidase.

Human umbilical vein endothelial cells (HUVECs) were pretreated with Co Q10 and then incubated with oxLDL for 24 h. Co Q10 attenuated oxLDL-elicited LOX-1 expression and ROS generation by suppression of NADPH oxidase activation. Co Q10 rescued dephosphorylation of AMPK caused by oxLDL that in turn led to an activation of NADPH oxidase by PKC. The results were confirmed using AMPK siRNA. Moreover, oxLDL-suppressed Akt/eNOS and enhanced p38 phosphorylation, which in turn activated NF-κB pathway. These detrimental events were ameliorated by Co Q10.

These results provide new highlight onto the possible molecular mechanisms of how Q10 suppresses oxLDL-induced endothelial oxidative injuries by the modulation of LOX-1-mediated ROS generation via the AMPK/PKC/NADPH oxidase signaling pathway.





PubMed ID: 21812107



    

CHEMISTRY & BIOLOGY 2012 OCT; 19 (10): 1222-36.


AMP-activated protein kinase: a target for drugs both ancient and modern.


Hardie DG, Ross FA, Hawley SA,



The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status. It is activated, by a mechanism requiring the tumor suppressor LKB1, by metabolic stresses that increase cellular ADP:ATP and/or AMP:ATP ratios. Once activated, it switches on catabolic pathways that generate ATP, while switching off biosynthetic pathways and cell-cycle progress. These effects suggest that AMPK activators might be useful for treatment and/or prevention of type 2 diabetes and cancer. Indeed, AMPK is activated by the drugs metformin and salicylate, the latter being the major breakdown product of aspirin. Metformin is widely used to treat diabetes, while there is epidemiological evidence that both metformin and aspirin provide protection against cancer. We review the mechanisms of AMPK activation by these and other drugs, and by natural products derived from traditional herbal medicines.



PubMed ID: 23102217



    

CELLULAR SIGNALLING 2012 NOV; 24 (11): 2216-25.


Wogonin induces apoptosis by activating the AMPK and p53 signaling pathways in human glioblastoma cells.


Lee DH, Lee TH, Jung CH, Kim YH,



We investigated the molecular basis of the ability of wogonin to control the intracellular signaling cascades of AMP-activated protein kinase (AMPK). This activity induces antitumor activities in glioblastoma multiforme (GBM) cells. Recently, the evolutionarily conserved serine/threonine kinase AMPK has emerged as a possible target for tumor control. We investigated the effects of wogonin on apoptosis regulation and the activation of AMPK. Wogonin treatment resulted in a series of antitumor effects such as cell death and apoptotic appearance. Activation of AMPK suppressed downstream substrates, such as the mammalian target of rapamycin (mTOR) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1), and resulted in a general decrease in translation. Moreover, wogonin-activated AMPK decreased the activity and/or expression of lipogenic enzymes such as acetyl-CoA carboxylase. Furthermore, in GBM cells, wogonin blocked cell cycle progression at the G1 phase and induced apoptosis by inducing p53 expression and further upregulating p21 expression. Taken together, our findings demonstrated that wogonin has the potential to be a chemopreventive and therapeutic agent against human GBM.



PubMed ID: 22846543



    

MOLECULAR NUTRITION & FOOD RESEARCH 2009 SEP; 53 (9): 1156-65.


EGCG inhibits protein synthesis, lipogenesis, and cell cycle progression through activation of AMPK in p53 positive and negative human hepatoma cells.


Huang CH, Tsai SJ, Wang YJ, Pan MH, Kao JY, Way TD,



In the previous studies, (-)-epigallocatechin-3-gallate (EGCG) has been shown to have anticarcinogenic effects via modulation in protein expression of p53. Using p53 positive Hep G2 and p53 negative Hep 3B cells, we found that treatment of EGCG resulted in dose-dependent inhibition of cellular proliferation, which suggests that the interaction of EGCG with p53 may not fully explain its inhibitory effect on proliferation. Caloric restriction (CR) reduces the incidence and progression of spontaneous and induced tumors in laboratory rodents. EGCG has multiple beneficial activities similar to those associated with CR. One key enzyme thought to be activated during CR is AMP-activated kinase (AMPK), a sensor of cellular energy levels. Here, we showed that EGCG activated AMPK in both p53 positive and negative human hepatoma cells. The activation of AMPK suppressed downstream substrates, such as mammalian target of rapamycin (mTOR) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1) and a general decrease in mRNA translation. Moreover, EGCG activated AMPK decreases the activity and/or expression of lipogenic enzymes, such as fatty acid synthase (FASN) and acetyl-CoA carboxylase (ACC). Interestingly, the decision between apoptosis and growth arrest following AMPK activation is greatly influenced by p53 status. In p53 positive Hep G2 cells, EGCG blocked the progression of cell cycle at G1 phase by inducing p53 expression and further up-regulating p21 expression. However, EGCG inducted apoptosis in p53 negative Hep 3B cells. Based on these results, we have demonstrated that EGCG has a potential to be a chemoprevention and anti-lipogenesis agent for human hepatoma cells.



PubMed ID: 19662644


 
 
 
 

PRKAA1

Protein kinase, AMP-activated, catalytic, alpha-1

5p13.1


Naturopathic Agents Known to Influence Entity Expression:
  • Scutellaria baicelensis
  • Gynostemma pentaphyllum
  • Ephedra herb
  • Green Tea, Kukicha, Bancha
  • Coptis rhizome
  • Wogonin
  • Epigallocatechin 3-gallate
  • Green Tea Polyphenol Extract
  • Skullcap (Scutellaria baicalensis)
  • Co-enzyme Q10
  • Bupleurum root
  • Coptis rhizome
  • Rheum palmatum
  • Salix alba (willow)
  • Laminaria japonica
  • Berberine


    

PLOS ONE 2011 ; 6 (2): E16556.


Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis.


Xia X, Yan J, Shen Y, Tang K, Yin J, Zhang Y, Yang D, Liang H, Ye J, Weng J,



Berberine (BBR) is a compound originally identified in a Chinese herbal medicine Huanglian (Coptis chinensis French). It improves glucose metabolism in type 2 diabetic patients. The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK) and improvement of insulin sensitivity. However, it is not clear if BBR reduces blood glucose through other mechanism. In this study, we addressed this issue by examining liver response to BBR in diabetic rats, in which hyperglycemia was induced in Sprague-Dawley rats by high fat diet. We observed that BBR decreased fasting glucose significantly. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK) and Glucose-6-phosphatase (G6Pase), were decreased in liver by BBR. Hepatic steatosis was also reduced by BBR and expression of fatty acid synthase (FAS) was inhibited in liver. Activities of transcription factors including Forkhead transcription factor O1 (FoxO1), sterol regulatory element-binding protein 1c (SREBP1) and carbohydrate responsive element-binding protein (ChREBP) were decreased. Insulin signaling pathway was not altered in the liver. In cultured hepatocytes, BBR inhibited oxygen consumption and reduced intracellular adenosine triphosphate (ATP) level. The data suggest that BBR improves fasting blood glucose by direct inhibition of gluconeogenesis in liver. This activity is not dependent on insulin action. The gluconeogenic inhibition is likely a result of mitochondria inhibition by BBR. The observation supports that BBR improves glucose metabolism through an insulin-independent pathway.



PubMed ID: 21304897


 

PRKAA2

Protein kinase, AMP-activated, alpha-2 catalytic subunit

1p32.2


Naturopathic Agents Known to Influence Entity Expression:
  • Scutellaria baicelensis
  • Gynostemma pentaphyllum
  • Ephedra herb
  • Green Tea, Kukicha, Bancha
  • Coptis rhizome
  • Wogonin
  • Epigallocatechin 3-gallate
  • Green Tea Polyphenol Extract
  • Skullcap (Scutellaria baicalensis)
  • Co-enzyme Q10
  • Bupleurum root
  • Coptis rhizome
  • Rheum palmatum
  • Salix alba (willow)
  • Laminaria japonica
  • Berberine