Ginsenoside Re

Ginsenoside Re inhibits Ca2+ accumulation in mitochondria during cardiac ischemia/reperfusion, which is attributable to nitric oxide (NO)-induced Ca2+ channel inhibition and K+ channel activation in cardiac myocytes. Ginsenoside Re activates endothelial NO synthase (eNOS) to release NO, resulting in activation of the slowly activating delayed rectifier K+ current. However, ginsenoside Re does not stimulate proliferation of androgen-responsive LNCaP cells and estrogen-responsive MCF-7 cells, implying that ginsenoside Re does not activate a genomic pathway of sex hormone receptors. ginsenoside Re induces phosphorylation of Akt in cardiomyocytes in a concentration-dependent manner. Ginsenoside Re is a partial agonist of the AR, ERα, and PR. It is a partial antagonist, but not an agonist, of the genomic pathway of AR or ERα^[1].

Cells are seeded in triplicate at a density of 1.6 × 10⁵ cells/ml in phenolred-free DMEM/F12 with 10% charcoal-treated fetal bovine serum. Five days after cells have been incubated in the presence of 17β-estradiol (E2; 10 nM), 5α-dihydrotestosterone (DHT; 10 nM), or ginsenoside Re (10 μM), they are collected and cell numbers are counted.

The absorption of Re is fast in gastrointestinal tract. Re may be metabolized mainly to Rh1 and F1 by intestinal microflora before absorption into blood; and Re is quickly cleared from the body. In cardiovascular system, Re possesses negative effects on cardiac contractility and autorhythmicity, anti-arrhythmic and anti-ischemic effects, angiogenic regeneration activities and cardiac electrophysiological functions. Re reaches peak concentration in plasma within about 45 minutes after oral administration of total panax notoginsenoside (TPNG) powder in rats, suggesting a rapid absorption in gastrointestinal tract. The absolute bioavailability of Re is 7.06%. In pharmacokinetic study using ICR mice, the time to reach the peak plasma concentration after oral administration is 0.4 ± 0.2 hour and the oral bioavailability is 0.19-0.28%. Re is rapidly cleared from the body within 0.2 ± 0.03 hour for male mice and 0.5 ± 0.08 hour for female mice after intravenous administration^[2]. Re administration in ob/ob mice significantly reduces fasting blood glucose levels, improves glucose tolerance and systemic insulin sensitivity without affecting body weight. These events are mediated, at least in part, by the changes in skeletal muscle gene expression^[3].