AMP-activated protein kinase: An emerging target for ginseng

Jeong, Kyong Ju; Kim, Go Woon; Chung, Sung Hyun

doi:10.1016/j.jgr.2013.11.014

Cited by 65 publications

(51 citation statements)

References 58 publications

(53 reference statements)

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“…The long chain isoform of 3-KAT is also bound to the inner mitochondrial membrane [24,25], however it is still unknown if trimetazidine must bind tightly to 3-KAT in order to inhibit enzyme activity. AMPK switches on catabolic pathways, such as the uptake of glucose and fatty acids, and their metabolism by mitochondrial oxidation and glycolysis [26]. In physiological conditions, AMPK modulates lipid metabolism by phosphorylating and inactivating acetyl-CoA carboxylase (ACC) [27].…”

Section: Discussionmentioning

confidence: 99%

The protective effect of trimetazidine on myocardial ischemia/reperfusion injury through activating AMPK and ERK signaling pathway

et al. 2016

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Introduction Trimetazidine (TMZ) is an anti-anginal drug that has been widely used in Europe and Asia. The TMZ can optimize energy metabolism via inhibition of long-chain 3-ketoacyl CoA thiolase (3-KAT) in the heart, with subsequent decrease in fatty acid oxidation and stimulation of glucose oxidation. However, the mechanism by which TMZ aids in cardioprotection against ischemic injury has not been characterized. AMP-activated protein kinase (AMPK) is an energy sensor that controls ATP supply from substrate metabolism and protects heart from energy stress. TMZ changes the cardiac AMP/ATP ratio by modulating fatty acid oxidation, thereby triggering AMPK signaling cascade that contributes to the protection of the heart from ischemia/reperfusion (I/R) injury. Methods The mouse model of in vivo regional ischemia and reperfusion by the ligation of the left anterior descending coronary artery (LAD) was used for determination of myocardial infarction. The infarct size was compared between C57BL/6J WT mice and AMPK kinase dead (KD) transgenic mice with or without TMZ treatment. The ex vivo working heart perfusion system was used to monitor the effect of TMZ on glucose oxidation and fatty acid oxidation in the heart. Results TMZ treatment significantly stimulates cardiac AMPK and extracellular signal-regulated kinase (ERK) signaling pathways (p < 0.05 vs. vehicle group). The administration of TMZ reduces myocardial infarction size in WT C57BL/6J hearts, the reduction of myocardial infarction size by TMZ in AMPK KD hearts was significantly impaired versus WT hearts (p < 0.05). Intriguingly, the administration of ERK inhibitor, PD98059, to AMPK KD mice abolished the cardioprotection of TMZ against I/R injury. The ex vivo working heart perfusion data demonstrated that TMZ treatment significantly activates AMPK signaling and modulating the substrate metabolism by shifting fatty acid oxidation to glucose oxidation during reperfusion, leading to reduction of oxidative stress in the I/R hearts. Therefore, both AMPK and ERK signaling pathways mediate the cardioprotection of TMZ against ischemic injury. The metabolic benefits of TMZ for angina patients could be due to the activation of energy sensor AMPK in the heart by TMZ administration.

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Section: Discussionmentioning

confidence: 99%

The protective effect of trimetazidine on myocardial ischemia/reperfusion injury through activating AMPK and ERK signaling pathway

et al. 2016

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“…Due to the diverse roles of AMPK in the cell as well as its regulation in several pathologic conditions, AMPK acts as a promising therapeutic target for the treatment of a number of pathologic conditions (Hardie, 2013;Russo et al, 2013;Jeong et al, 2014). There are several known physiologic, pharmacological, natural, and hormone activators of AMPK, with some of these already being used clinically (Corton et al, 1995;Zhou et al, 2001;Lee et al, 2006).…”

Section: Therapeutic Targeting Of the Ampk Signaling Pathwaymentioning

confidence: 99%

Adenosine Monophosphate–Activated Kinase and Its Key Role in Catabolism: Structure, Regulation, Biological Activity, and Pharmacological Activation

2014

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Adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy sensor, which once activated, plays a role in several processes within the cell to restore energy homeostasis. The protein enhances catabolic pathways, such as b-oxidation and autophagy, to generate ATP, and inhibits anabolic processes that require energy, including fatty acid, cholesterol, and protein synthesis. Due to its key role in the regulation of critical cellular pathways, deregulation of AMPK is associated with the pathology of many diseases, including cancer, Wolff-Parkinson-White syndrome, neurodegenerative disorders, diabetes, and metabolic syndrome. In fact, AMPK is a target of some pharmacological agents implemented in the treatment of diabetes (metformin and thiazolidinediones) as well as other naturally derived products, such as berberine, which is used in traditional medicine. Due to its critical role in the cell and the pathology of several disorders, research into developing AMPK as a therapeutic target is becoming a burgeoning and exciting field of pharmacological research. A profound understanding of the regulation and activity of AMPK would enhance its development as a promising therapeutic target.

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“…Data ini menunjukkan bahwa diduga mekanisme kerja ekstrak daun Singawalang dalam menurunkan kadar glukosa darah adalah melalui AMPK-α1. Penelitian lain juga menunjukkan bahwa obat herbal seperti panax gingseng, 32 curcumin, berberine dari coptis chinesis, 33 epigallocathecin gallat dari teh hijau, hispidulin dari snow lotus merupakan obat herbal yang digunakan untuk terapi diabetes dan mekanisme kerjanya melalui aktivasi AMPK. 34 Senyawa polifenol yaitu Salvianolic acid yang diisolasi dari akar tumbuhan Salvia milttiorriza juga mempunyai aktivitas sebagai antidiabetik melalui aktivasi AMPK.…”

Section: Pembahasanunclassified

Effect of Petiveria alliacea Leaves Extract in Decreasing Serum Level of Blood Glucose Level Through Activation of AMPK-α1 in Diabetes Mellitus Rat Models

Mustika

Indrawati

Sari

2017

Indones J Clin Pharm

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AbstrakSingawalang (Petiveria alliaceae) adalah tumbuhan yang banyak ditemukan di Indonesia dan secara empiris digunakan oleh penduduk untuk mengobati diabetes melitus. Hingga saat ini, penelitian tentang pengaruh dan mekanisme ekstrak daun Singawalang dalam menurunkan kadar glukosa darah belum banyak dilakukan. Tujuan penelitian ini adalah untuk mengetahui pengaruh ekstrak daun Singawalang terhadap penurunan kadar glukosa darah dan ekspresi AMPK-α1 pada hati. Jenis penelitian ini adalah penelitian eksperimental dengan rncangan acak lengkap. Penelitian dilakukan di Laboratorium Farmakologi dan Terapi dan Laboratorium Patologi Anatomi Fakultas Kedokteran Universitas Airlangga pada bulan April-Agustus 2015. Hewan coba tikus strain Rattus norvegicus dibuat model diabetes melitus, diinduksi dengan Streptozotocin. Sebanyak 25 tikus model diabetes melitus dibagi secara acak menjadi 5 kelompok. Kelompok perlakuan 1, 2 dan 3 adalah kelompok yang memperoleh ekstrak daun Singawalang dengan dosis 90 mg/kgbb, 180 mg/kgbb dan 360 mg/kgbb. Kelompok kontrol positif adalah kelompok yang memperoleh metformin dengan dosis 150 mg/kgbb dan kontrol negatif adalah kelompok tikus yang memperoleh vehikulum. Ekstrak dan metformin diberikan sehari sekali, personde selama 14 hari. Pada hari ke-15 setelah terapi, tikus diperiksa kadar glukosa darah dan dieuthanasia untuk diambil organnya. Ekspresi AMPK-α1 dinilai menggunakan imunohistokima. Data yang terkumpul dianalisis dengan ANAVA dan Wilcoxon (α=0,05). Hasil penelitian menunjukkan adanya perbedaan kadar glukosa darah yang bermakna antara kontrol negatif dengan dosis 90 mg/kgbb, dosis 360 mg/kgbb, dan kontrol positif, antara dosis 180 mg/kgbb dengan dosis 360 mg/kgbb dan kontrol positif. Analisis terhadap ekspresi AMPK-α1 pada hati tikus menunjukkan perbedaan yang bermakna antara dosis 180 mg/kgbb dengan dosis 360 mg/kgbb dan kontrol positif. Simpulan dari penelitian ini adalah ekstrak Singawalang dapat menurunkan kadar glukosa darah pada tikus model diabetes melitus melalui aktivasi AMPK-α1.Kata kunci: AMPK-α1, diabetes melitus, kadar glukosa darah, Singawalang Effect of Petiveria alliacea Leaves Extract in Decreasing Serum Level of Blood Glucose Level Through Activation of AMPK-α1 in Diabetes MellitusRat Models Abstract Singawalang (Petiveria alliaceae) is a medicinal herb that is used traditionally as folk medicine for various diseases. The plant has been used as an antidiabetic agent in Indonesian society. Until now, the effect and mechanism of action of Petiveria alliaceae as antidiabetic agent is not clear. The aim of the study was to determine the effect of Petiveria alliaceae to blood glucose level and to identify expression of AMPK-α1 in rat liver. The research was experimental study with randomized and was conducted at Laboratory Pharmacology and Therapy, and Laboratory Patology Anatomy, Faculty of Medicine, Universitas Airlangga, on April until August 2015. Twenty five male rats were injected by Streptozotocin to create diabetic rat models and randomly divided into 5 groups. ...

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AMP-activated protein kinase: An emerging target for ginseng

Cited by 65 publications

References 58 publications

The protective effect of trimetazidine on myocardial ischemia/reperfusion injury through activating AMPK and ERK signaling pathway

The protective effect of trimetazidine on myocardial ischemia/reperfusion injury through activating AMPK and ERK signaling pathway

Adenosine Monophosphate–Activated Kinase and Its Key Role in Catabolism: Structure, Regulation, Biological Activity, and Pharmacological Activation

Effect of Petiveria alliacea Leaves Extract in Decreasing Serum Level of Blood Glucose Level Through Activation of AMPK-α1 in Diabetes Mellitus Rat Models

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