Major ginsenosides from Panax ginseng promote aerobic cellular
respiration and SIRT1-mediated mitochondrial biosynthesis in
cardiomyocytes and neurons
Abstract
Aerobic cellular respiration provides chemical energy, adenosine
triphosphate (ATP), to maintain multiple cellular functions. Sirtuin 1
(SIRT1) can deacetylate peroxisome proliferator-activated receptor gamma
coactivator 1 alpha (PGC-1α) to promote mitochondrial biosynthesis.
Targeting energy metabolism is a potential strategy for the prevention
and treatment of various diseases, such as cardiac and neurological
disorders. Ginsenosides, one of the major bioactive constituents of
Panax ginseng, have been extensively used due to their diverse
beneficial effects on healthy subjects and patients with different
diseases. However, the underlying molecular mechanisms of total
ginsenosides (GS) on energy metabolism remain unclear. In this study,
oxygen consumption rate, ATP production, mitochondrial biosynthesis,
glucose metabolism, and SIRT1-PGC-1α pathways in untreated and
GS-treated different cells, fly, and mouse models were investigated. GS
pretreatment enhanced mitochondrial respiration capacity and ATP
production in aerobic respiration-dominated cardiomyocytes and neurons,
and promoted tricarboxylic acid metabolism in cardiomyocytes. Moreover,
GS clearly enhanced NAD+-dependent SIRT1 activation to increase
mitochondrial biosynthesis in cardiomyocytes and neurons, which was
completely abrogated by nicotinamide. In addition, GS had protective
effects against hypoxia- or oxygen-glucose deprivation-induced
cardiomyocyte damage through activation of the SIRT1-PGC-1α pathway.
Importantly, ginsenoside monomers, such as Rg1, Re, Rf, Rb1, Rc, Rh1,
Rb2, and Rb3, were found to activate SIRT1 and promote energy
metabolism. This study may provide new insights into the extensive
application of ginseng for cardiac and neurological protection in
healthy subjects and patients with ischemic disorders.