The 1,4-naphthoquinone derivative from Pyrola rotundifolia activates AMPK phosphorylation in C2C12 myotubes

An aqueous ethanol extract of Pyrola rotundifolia L. induced AMP-activated protein kinase (AMPK) phosphorylation in C2C12 myotubes. The bioassay-guided fractionation of the extract led to the isolation a 2-methyl-7-hydroxymethyl-1,4-naphthoquinone, or a 7'-hydroxy-chimaphilin, which showed concentration-dependent AMPK phosphorylation activity at 2.5-20 mu g/ml. At a concentration of 10 mu g/ml (50 mu M), an approximately four-fold increase in the AMPK alpha(Thr(172)) phosphorylation level was observed. The stimulatory effect of naphthoquinone on AMPK activity was comparable to that of known compounds found in natural sources that activate the AMPK signaling pathway. (C) 2011 Elsevier B.V. All rights reserved.