AMP-activated protein kinase (AMPK) activators from Myristica fragrans (nutmeg) and their anti-obesity effect.
AMP-activated protein kinase (AMPK) is a potential therapeutic target for the treatment of metabolic syndrome including obesity and type-2 diabetes. As part of an ongoing search for new AMPK activators from plants, this study found that the total extract of Myristica fragrans (nutmeg) activated the AMPK enzyme in differentiated C2C12 cells. As active constituents, seven 2,5-bis-aryl-3,4-dimethyltetrahydrofuran lignans, tetrahydrofuroguaiacin B (1), saucernetindiol (2), verrucosin (3), nectandrin B (4), nectandrin A (5), fragransin C(1) (6), and galbacin (7) were isolated from this extract. Among the isolates, compounds 1, 4, and 5 at 5 microM produced strong AMPK stimulation in differentiated C2C12 cells. In addition, the preventive effect of a tetrahydrofuran mixture (THF) on weight gain in a diet-induced animal model was further examined. These results suggest that nutmeg and its active constituents can be used not only for the development of agents to treat obesity and possibly type-2 diabetes but may also be beneficial for other metabolic disorders.
Nguyen
Phi Hung
PH
BK21 Project Team, College of Pharmacy, Chosun University, Gwangju 501-759, Republic of Korea.
Le
Thi Van Thu
TV
Kang
Hu Won
HW
Chae
Jooyoung
J
Kim
Sang Kyum
SK
Kwon
Kwang-iI
KI
Seo
Dae Bang
DB
Lee
Sang Jun
SJ
Oh
Won Keun
WK
D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D019440:Anti-Obesity Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D020536:Enzyme Activators / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D026323:Myristica / Q000737:chemistry*
D019440:Anti-Obesity Agents; D020536:Enzyme Activators; D055372:AMP-Activated Protein Kinases