In silico design for adenosine monophosphate-activated protein kinase agonist from traditional chinese medicine for treatment of metabolic syndromes.

Hsin-Chieh Tang,Calvin Yu-Chian Chen

doi:10.1155/2014/928589

Abstract

Adenosine monophosphate-activated protein kinase (AMPK) acts as a master mediator of metabolic homeostasis. It is considered as a significant millstone to treat metabolic syndromes including obesity, diabetes, and fatty liver. It can sense cellular energy or nutrient status by switching on the catabolic pathways. Investigation of AMPK has new findings recently. AMPK can inhibit cell growth by the way of autophagy. Thus AMPK has become a hot target for small molecular drug design of tumor inhibition. Activation of AMPK must undergo certain extent change of the structure. Through the methods of structure-based virtual screening and molecular dynamics simulation, we attempted to find out appropriate small compounds from the world's largest TCM Database@Taiwan that had the ability to activate the function of AMPK. Finally, we found that two TCM compounds, eugenyl_beta-D-glucopyranoside and 6-O-cinnamoyl-D-glucopyranose, had the qualification to be AMPK agonist.

Highlights

One study has found that the cell “starvation” signal transduction pathway reveals the process of cell “starvation” signal transduction mechanisms
Traditional Chinese medicine (TCM) Database@Taiwan that had the ability to activate the function of AMPK [69]
Ramachandran plot of AMPK-modeled structure showed that 91.7% of residues were in the favored area, 5.9% were in the allowed area, and only 2.4% were in the disallowed area (Figure 2)

Summary

Introduction

One study has found that the cell “starvation” signal transduction pathway reveals the process of cell “starvation” signal transduction mechanisms This finding is considered as a significant millstone to treat metabolic syndromes including obesity, diabetes, and fatty liver [1, 2]. The effect of AMPK activation is switching on the catabolic pathways consisting of cellular glucose uptake, glycolysis, fatty acid oxidation, inhibition of triglyceride, cholesterol, and protein synthesis [8, 9]. The upstream signal molecule, such as adiponectin, stimulates AMPK to utilize glucose and fatty acid [10]. Adiponectin stimulates AMPK to protect the heart against myocardial ischemia [13, 14] Another upstream signal molecule, leptin, activates AMPK to stimulate fatty acid oxidation [15]. AMPK in the hypothalamus mediates thyroid hormone to regulate energy balance, too [16]

Methods

Results

Conclusion