Notably, because protein synthesis requires a myriad of cellular energy, AMPK activation induced by metabolic selleck compound stress significantly inhibits protein synthesis, resulting in AMPK–mTORC1 crosstalk: AMPK attenuates mTORC1 signaling through phosphorylation and activation of tuberous sclerosis 2 [7], a negative regulator of mTORC1. AMPK also directly phosphorylates Raptor, which induces 14-3-3 binding to raptor and repression of mTORC1 activity [8]. Other findings

that AMPK caused the inhibition of progress through the cell cycle [9], and that the mechanism of AMPK activation required the presence of the tumor suppressor LKB1 [10], [11] and [12] also gave us the idea that AMPK activators might be beneficial in the prevention and/or treatment of cancer. AMPK activation switches off all of these pathways and would therefore be expected to exert an antitumor effect, reinforced by its ability to cause cell-cycle

arrest. These effects of AMPK might explain the tumor suppressor effects of the upstream kinase LKB1 [13], as well as findings that metformin usage reduces PD-1/PD-L1 activation the risk of cancer in diabetics [14] and that metformin and other AMPK activators (phenformin, A-769662) delay the onset of tumorigenesis in a mouse model [15]. Over recent years, a plethora of naturally occurring compounds including ginseng and ginsenosides have been reported to activate AMPK in intact cells. These natural products include resveratrol from grapes [16], epigallocatechin-3-gallate (EGCG) from green tea and capsaicin from chili peppers [17], curcumin from turmeric [18], as well as four compounds derived from traditional Chinese medicine, berberine from Chinese Goldthread [19], hispidulin from Snow Lotus [20],

licochalcone A from Glycyrrhiza and Brassica rapa [21], and betulinic acid from Betula [22]. Ginseng is one of the FAD most popular and bestselling herbal medicines worldwide. Ginseng has been used as a medicine and/or as a neutraceutical by healthy and ill individuals all around the world. Many clinical and animal studies on ginseng have been performed to characterize its therapeutic properties, which include improving physical performance [23] and [24] and sexual function [25] and [26], treating cancer [27] and [28], diabetes [29], [30] and [31], and hypertension [32] and [33]. In this article, we review the mechanisms by which AMPK is activated by ginseng extracts or ginsenosides, well-known active components found in ginseng. Ginseng was used for preventing and/or treating metabolic disorders and cancer prior to when it was realized that ginseng and ginsenosides seem to be AMPK activators. AMPK activators derived from medicinal plants have disparate chemical structures and it was difficult to see how they activate AMPK.