Abstract
Background and Purpose : 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. Experimental Approach : 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. Key
Results : 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. Conclusion and Implications : GS
promotes aerobic cellular respiration and SIRT1-mediated mitochondrial
biosynthesis, which may provide new insights into the extensive
application of ginseng for cardiac and neurological protection in
healthy subjects and patients with ischemic disorders.
Key Words : ginsenosides, aerobic cellular respiration,
mitochondrial biosynthesis, SIRT1, PGC1α, cardiomyocytes, neurons