Ginsenoside Rb3 strengthens the hypoglycemic effect through AMPK for inhibition of hepatic gluconeogenesis

Abstract

Abstract. Ginsenoside Rb3 is one of the major active components in protopanaxdiol type ginsenosides, and has demonstrated anti-diabetic activity. However, the mechanism of this action has yet to be elucidated. The present study investigated the effects of ginsenoside Rb3 on the AMP-activated protein kinase (AMPK) gluconeogenesis pathway. The present study involved the use of HepG2 cells and western blot analysis to systematically evaluate the effect of ginsenoside Rb3 on AMPK signaling proteins and key factors of gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase, forkhead transcription factor 1 (FOXO1) and hepatic nuclear receptor 4α (HNF4α)]. The results indicated that 25 µM ginsenoside Rb3 significantly activated AMPK activity, increased the ratio of p-AMPK/total-AMPK, and had synergistic effects with the activator of AICAR on the activation of AMPK. Further analysis indicated that the expression of the transcription factor FOXO1 and HNF4α protein, two important factors in the pathway of HepG2 cell gluconeogenesis, was significantly suppressed by ginsenoside Rb3. PEPCK and G6Pase were subsequently inhibited, which led to the suppression of gluconeogenesis. These effects were partially blocked by the AMPK inhibitor, Compound C, which indicated that the inhibition effects of ginsenoside Rb3 on hepatic gluconeogenesis were predominantly due to the activation of the AMPK signaling pathway. These data suggested that ginsenoside Rb3 can suppress hepatic gluconeogenesis, at least partially through stimulation of AMPK activity.

Effect of Red Ginseng Extract on the Pharmacokinetics and Efficacy of Metformin in Streptozotocin-Induced Diabetic Rats

“…The mechanisms underlying the modulation of glucose metabolism by RGE in patients with DM would likely be perturbation of hepatic glucose production and enhancement of glucose uptake through glucose transporter 4 (GLUT4) into peripheral tissues. Recently, ginsenosides Rb1, Rb2, Rg1, Rg3, Rh2, and compound K, major pharmacological components of RGE, have been reported to suppress the hepatic gluconeogenesis via adenosine monophosphate (AMP)-activated protein kinase (AMPK) [ 22 , 23 , 24 ]. Importantly, enhanced GLUT4 expression mediated by activated insulin receptor substrate (IRS)/phosphatidylinositol-3,4,5-triphosphate (PI3K)/serine-threonine protein kinase signaling pathway by the treatment of RGE or ginsenosides increased glucose uptake in adipocytes or skeletal muscle cells and, thereby, decreased blood glucose or Hb-A1c levels [ 22 , 25 ].…”

Therapeutic Potential of Ginsenosides as an Adjuvant Treatment for Diabetes

“…Some ginsenosides exert blood glucose lowering effects in this way. Researches confirmed that ginsenoside Rg1 (Liu et al, 2017 ), Rb3 (Meng et al, 2017 ) and, compound K (Wei et al, 2015 ) reduced gluconeogenesis through increased AMPK expression and decreased FOXO1 activity, which may offer a potential treatment for type 2 diabetes. Ginsenoside Rg5 prevented gluconeogenesis via the suppressing of HIF-1α (Xiao et al, 2017 ) expression.…”

20(s)‑ginseonside‑Rg3 modulation of AMPK/FoxO3 signaling to attenuate mitochondrial dysfunction in a dexamethasone‑injured C2C12 myotube‑based model of skeletal atrophy in vitro

“…MTT assays were conducted to monitor cell viability ( 27 , 28 ) as follows: C2C12 myotubes treated for 24 to 48 h with various concentrations of DEX (0, 25, 50, 100 or 200 µM) ( 29 ) or with S-Rg3 (0, 0.02, 0.2 or 2 µM) and/or DEX (200 µM) for 24 h were incubated with MTT (0.5 mg/ml) for 4 h. All treatments were conducted at 37°C. Next, formazan dissolved in 150 µl DMSO was added to wells then measurements of absorbance levels of wells were taken at a wavelength of 490 nm at room temperature.…”