Rhodiola crenulata extract suppresses hepatic gluconeogenesis via activation of the AMPK pathway.
BACKGROUND
Rhodiola, a popular herb, has been used for treating high altitude sicknesses, depression, fatigue, and diabetes. However, the detailed mechanisms by which Rhodiola crenulata functions in the liver need further clarification.


OBJECTIVE
The current study was designed to examine the effects of Rhodiola crenulata root extract (RCE) on hepatic glucose production.


METHODS
Human hepatoma HepG2 cells were treated with RCE for 6 h. Glucose production, the expression level of p-AMPK, and the expression of key gluconeogenic genes were measured. The effects of RCE were also studied in Sprague-Dawley (SD) rats. The efficacy and underlying mechanism of RCE in the liver were examined.


RESULTS
RCE significantly suppressed glucose production and gluconeogenic gene expression in HepG2 cells while activating the AMPK signaling pathway. Interestingly, RCE-suppressed hepatic gluconeogenesis was eliminated by an AMPK-specific inhibitor, but not by the PI3K/AKT-specific inhibitor. In addition, oral administration of RCE significantly increased phosphorylated AMPK levels and inhibited gluconeogenic gene expression in the rat liver. Furthermore, RCE treatment also decreased plasma glucose concentration in rats.


CONCLUSIONS
We present in vitro and in vivo evidence that RCE might exert the glucose-lowering effect partly by inhibiting hepatic gluconeogenesis through activating the AMPK signaling pathway. These findings provide evidence that Rhodiola crenulata may be helpful for the management of type II diabetes.
Institute of Aerospace and Undersea Medicine, National Defense Medical Center, Taipei, Taiwan. Electronic address: leeshihyuno1@mail.ndmctsgh.edu.tw.
Shih-Yu
SY
Lee
Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan. Electronic address: rocodo29@hotmail.com.
Feng-Yi
FY
Lai
Department of Biotechnology, National Formosa University, Yunlin, Taiwan. Electronic address: lsshi@sunws.nfu.edu.tw.
Li-Shian
LS
Shi
School of Public Health, National Defense Medical Center, Taipei, Taiwan. Electronic address: trishow@mail.ndmctsgh.edu.tw.
Yu-Ching
YC
Chou
School of Pharmacy, National Defense Medical Center, Taipei, Taiwan. Electronic address: yenichuan@mail.ndmctsgh.edu.tw.
I-Chuan
IC
Yen
Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan; Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan. Electronic address: tcchang@mail.ndmctsgh.edu.tw.
Tsu-Chung
TC
Chang
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005943:Gluconeogenesis / Q000187:drug effects*; D005947:Glucose / Q000378:metabolism; D005960:Glucosides / Q000737:chemistry; D056945:Hep G2 Cells; D006801:Humans; D008099:Liver / Q000187:drug effects*; D008297:Male; D010636:Phenols / Q000737:chemistry; D010766:Phosphorylation; D010936:Plant Extracts / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D017207:Rats, Sprague-Dawley; D029771:Rhodiola / Q000737:chemistry*; D015398:Signal Transduction / Q000187:drug effects
D001786:Blood Glucose; D005960:Glucosides; D010636:Phenols; D010936:Plant Extracts; D047428:Protein Kinase Inhibitors; D055372:AMP-Activated Protein Kinases; D005947:Glucose; C009172:rhodioloside
AMPK; Hepatic gluconeogenesis; Rhodiola crenulata