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通过能量平衡调节新陈代谢。AMPK激活作为新陈代谢的主要调节剂，在肝，骨骼肌，心脏以及中枢神经系统（CNS）等关键组织中发挥作用。间接激活剂对酶的激活引起了科学的关注，以治疗糖尿病，肥胖症，癌症以及其他相关的代谢性疾病，例如中枢神经系统的生理和病理生理状态。据报道，许多激素和药物可激活AMPK，包括帕罗西汀，二甲双胍，噻唑烷二酮，脂联素，瘦素，白介素6等。AMPK活性在调节葡萄糖，脂质，以及蛋白质的代谢以及线粒体的生物发生和自噬。肝脏中AMPK的激活可降低血糖，而骨骼肌中的AMPK则可通过调节几种下游底物的活性而独立于胰岛素刺激葡萄糖摄取。AMPK的激活抑制合成并诱导脂肪酸氧化，这可能减少异位脂质蓄积并改善胰岛素作用。酶的活化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信号传导可能通过调节细胞周期检查点与癌症发展相关。许多常规药物均来自自然资源，而这种富有成果的化学结构来源的应用尚未得到深入研究。