Department of Pharmacognosy, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran; Medicinal Plants Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran.
Applied Biotechnology Research Center, Baqiyatallah University of Medical Sciences, Tehran, Iran.
Food Chem Toxicol. 2018 Dec;122:69-79. doi: 10.1016/j.fct.2018.09.079. Epub 2018 Oct 2.
Adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK) is a heterotrimeric enzyme which monitors cellular energy status and regulates metabolism with energy balance. AMPK activation, as a master regulator of metabolism, plays role in key tissues like liver, skeletal muscles, and heart as well as central nervous system (CNS). Activation of the enzyme by indirect activators attracts scientific attentions to treat diabetes, obesity, cancer, and other related metabolic disorders like physiological and pathophysiological states in CNS. A number of hormones and pharmacological agents have been reported to activate AMPK including paroxetine, metformin, thiazolidinediones, adiponectin, leptin, interleukin-6, and etc. AMPK activity is prominent in regulation of glucose, lipid, and proteins metabolism as well as mitochondrial biogenesis and autophagy. Activation of AMPK in the liver decrease blood glucose and in skeletal muscles stimulates glucose uptake independently of insulin through modulation of activity of several downstream substrates. Activation of AMPK inhibits synthesis and induces oxidation of fatty acids, which may reduce ectopic lipid accumulation and improve insulin action. The enzyme activation promotes cardiovascular homeostasis by ensuring optimum redox balance of heart and vascular tissue. In addition, AMPK signaling may link to cancer development via regulation of checkpoints of cell cycle. Numerous of conventional drugs have been derived from natural resources, while the application of this fruitful source of chemical structures have not been explored in depth. A number of these compounds are discussed in this review that exhibit beneficial effects in metabolic disorders through AMPK activation.
腺苷 5'-单磷酸 (AMP)-激活的蛋白激酶 (AMPK) 是一种异三聚体酶，可监测细胞能量状态并调节代谢与能量平衡。AMPK 的激活作为代谢的主要调节剂，在肝脏、骨骼肌和心脏等关键组织以及中枢神经系统 (CNS) 中发挥作用。间接激活剂对酶的激活引起了科学界对治疗糖尿病、肥胖症、癌症和其他相关代谢紊乱的关注，如 CNS 中的生理和病理状态。已经报道了许多激素和药理学药物可以激活 AMPK，包括帕罗西汀、二甲双胍、噻唑烷二酮类、脂联素、瘦素、白细胞介素-6 等。AMPK 活性在调节葡萄糖、脂质和蛋白质代谢以及线粒体生物发生和自噬方面非常突出。AMPK 在肝脏中的激活可降低血糖，在骨骼肌中可通过调节几种下游底物的活性来独立于胰岛素刺激葡萄糖摄取。AMPK 的激活抑制脂肪酸的合成并诱导其氧化，这可能减少异位脂质积累并改善胰岛素作用。该酶的激活通过确保心脏和血管组织的最佳氧化还原平衡来促进心血管稳态。此外，AMPK 信号可能通过调节细胞周期的检查点与癌症的发展有关。许多传统药物都源自天然资源，而这种丰富的化学结构来源的应用尚未得到深入探索。本文综述了一些化合物，这些化合物通过激活 AMPK 在代谢紊乱中表现出有益作用。
