Selected compounds derived from Moutan Cortex stimulated glucose uptake and glycogen synthesis via AMPK activation in human HepG2 cells.
OBJECTIVE
To evaluate the effect of selected compounds derived from Moutan Cortex on glucose uptake and glycogen synthesis associated with AMPK activation in insulin-resistant human HepG2 cell.


METHODS
The effect of isolated compounds (1-16) on glucose uptake and glycogen synthesis was performed using HepG2 cells. The western blot was used to determine the expression of AMPK and its downstream substrates, ACC, p-ACC, and p-GSK-3beta.


RESULTS
The effects of the 16 compounds from Moutan Cortex on glucose metabolism in HepG2 cells under high glucose conditions were evaluated. Compounds 2, 3, and 6 displayed highly potent effects on the stimulation of glucose uptake and glycogen synthesis in human HepG2 cells under high glucose conditions. Compounds 2, 3, and 6 phosphorylate AMPK (AMP-activated protein kinase), and resulted in increased phosphorylation of GSK-3beta and suppression of lipogenic expression (ACC and FAS) in a dose-dependent manner. Compounds 2, 3, and 6 also demonstrated interesting, strong eNOS phosphorylation in human umbilical vein endothelial cells (HUVECs). Compounds 1, 4, 5-12, and 14 displayed considerable effects on hepatic glucose production, AMPK activation, and phosphorylation of GSK-3beta in HepG2 cells under high glucose conditions.


CONCLUSIONS
These effects may indicate that the activation of AMPK by the active compounds from Moutan Cortex has considerable potential for reversing the metabolic abnormalities associated with type-2 diabetes.
Ha
Do Thi
do T
College of Pharmacy, Chungnam National University, Daejeon, Republic of Korea.
Trung
Trinh Nam
TN
Hien
Tran Thi
TT
Dao
Trong Tuan
TT
Yim
Namhui
N
Ngoc
Tran Minh
TM
Oh
Won Keun
WK
Bae
KihWan
K
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004365:Drugs, Chinese Herbal / Q000737:chemistry / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000378:metabolism; D064429:Fatty Acid Synthases / Q000037:antagonists & inhibitors; D005947:Glucose / Q000378:metabolism*; D006003:Glycogen / Q000096:biosynthesis*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D056945:Hep G2 Cells; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D029596:Paeonia / Q000737:chemistry; D010766:Phosphorylation; D024301:Plant Bark; D018517:Plant Roots; D014471:Umbilical Veins
D004365:Drugs, Chinese Herbal; D007004:Hypoglycemic Agents; C038881:moutan cortex; D006003:Glycogen; D052250:Nitric Oxide Synthase Type III; D064429:Fatty Acid Synthases; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3; D055372:AMP-Activated Protein Kinases; D000103:Acetyl-CoA Carboxylase; D005947:Glucose