Ginsenoside monomers increase mitochondrial function in
cardiomyocytes by activating the SIRT1 pathway
As we showed, GS are a complex mixture of ginsenoside monomers of
different proportions (Supplementary Fig. 1-2) . To further gain
insight into which ginsenoside in GS promotes mitochondrial function
through increased glucose oxidation and SIRT1 activation, we performed a
series of experiments to investigate the effects of different
ginsenosides on basal OCR, ATP content, and key protein levels in H9c2
cells. Similar to that of GS, different ginsenoside monomers, such as
Rg1, Re, Rf, Rb1, Rc, Rh1, Rb2, Rb3, Rd, S-Rg3, R-Rg3, and Rk1, at
individual concentrations of GS increased basal OCR in H9c2 cells after
48 h treatment compared with the control group (Fig. 8A) .
Moreover, ATP content was higher in Re-, Rf-, Rb1-, Rc-, Rh1-, Rb2-, or
Rb3-treated H9c2 cells than the control or GS group (Fig. 8B) .
These results confirm that these ginsenosides can promote mitochondrial
energy metabolism. Additionally, key proteins of the glucose oxidation
process, HK-II and MPC1, were increased by Rg1, Re, Rf, and Rc, which
was similar to GS (Fig. 8C-8D) . For SIRT1 expression, we found
that the level of SIRT1 was upregulated by most of the ginsenoside
monomers, with the exception of Rk3 (Fig. 8C-8D) . Especially,
ginsenosides Rg1, Re, Rc, Rh1, Rb2, and Rb3 had a similar role in
increasing SIRT1 expression as GS (Fig. 8C-8D) . Taken
together, these results identified
the major ginsenosides in GS, including Rg1, Re, Rf, Rb1, Rc, Rh1, Rb2,
and Rb3, which promote aerobic cellular respiration and SIRT1-mediated
mitochondrial biosynthesis to protect cardiomyocytes.