Ginsenoside Rg1 inhibits glucagon-induced hepatic gluconeogenesis through Akt-FoxO1 interaction.

Theranostics. 2017 ;7(16):4001-4012. Epub 2017 Sep 20. PMID: 29109794 Abstract Title: 
Ginsenoside Rg1 Inhibits Glucagon-Induced Hepatic Gluconeogenesis through Akt-FoxO1 Interaction. Abstract: 
Glucagon is involved in hepatic gluconeogenesis, playing a key role in type 2 diabetes. Ginsenosides are reported to have antidiabetic activities. Ginsenoside Rg1 is a major propanaxatriol-type saponin in ginseng. This study aims to investigate the regulatory effects of Rg1 on glucagon-induced hepatic glucose production.The effects of Rg1 were investigated in high-fat-diet (HFD)-fed mice and glucagon-challenged C57BL/6J mice. Glucose metabolism was evaluated by oral glucose tolerance test and pyruvate tolerance test. The role of Rg1 on the regulation of Akt-FoxO1 interaction was performed using immunofluorescence, immunoprecipitation, siRNA silencing, pharmacological inhibitor and active-site mutant in primary hepatocytes or HepG2 cells.Abnormally elevated fasting glucagon levels were observed in HFD-fed mice, contributing significantly to increased fasting plasma glucose levels. Inappropriate fasting glucagon secretion inactivated Akt and promoted hepatic glucose productionupregulation of FoxO1 activity. Rg1 preserved glucagon-impaired Akt activation partly by binding to Akt at Ser473 site. Rg1 also promoted Akt binding to FoxO1 and inactivated FoxO1 by phosphorylation. Consequently, Rg1 decreased the hepatic glucose production through a decrease in transcription of phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase). Both siRNA silencing of Akt and Akt inhibitor triciribine attenuated the effects of Rg1 in response to fasting hormone glucagon.Akt phosphorylation at Ser473 by ginsenoside Rg1 is critical for its gluconeogenesis-lowering effect, suggesting a potential for pharmaceutical intervention in response to fasting hormone glucagon. read more

Ginsenoside Rg1 attenuates cigarette smoke-induced pulmonary epithelial-mesenchymal transition.

Biomed Res Int. 2017 ;2017:7171404. Epub 2017 Aug 13. PMID: 29104873 Abstract Title: 
Ginsenoside Rg1 Attenuates Cigarette Smoke-Induced Pulmonary Epithelial-Mesenchymal Transition via Inhibition of the TGF-1/Smad Pathway. Abstract: 
Epithelial-mesenchymal transition (EMT) is a process associated with airway remodeling in chronic obstructive pulmonary disease (COPD), which leads to progressive pulmonary a traditional herbal medicine that has been shown to improve pulmonary function and exercise capacity in patients with COPD. Ginsenoside Rg1 is one of the main active components and was shown to inhibit oxidative stress and inflammation. The present study investigated the hypothesis that ginsenoside Rg1 attenuates EMT in COPD rats induced by cigarette smoke (CS) and human bronchial epithelial (HBE) cells exposed to cigarette smoke extract (CSE). Our data showed that CS or CSE exposure increased expression of the mesenchymal marker-smooth muscle actin (-SMA) and decreased expression of the epithelial marker epithelial cadherin (E-cad) in both lung tissues and HBE cells, which was markedly suppressed by ginsenoside Rg1. Importantly, CS-induced upregulation of TGF-1/Smad pathway components, including TGF-1, TGF-R1, phospho-Smad2, and phospho-Smad3, was also inhibited by ginsenoside Rg1. Additionally, ginsenoside Rg1 mimicked the effect of SB525334, a TGF-R1-Smad2/3 inhibitor, on suppression of EMT in CSE-induced HBE cells. Collectively, we concluded that ginsenoside Rg1 alleviates CS-induced pulmonary EMT, in both COPD rats and HBE cells, via inhibition of the TGF-1/Smad pathway. read more