AMP-activated protein kinase (AMPK) activators from Myristica fragrans (nutmeg) and their anti-obesity effect

Nguyen, Phi Hung; Le, Thi Van Thu; Kang, Hu; Chae, Jongchul; Kim, Sang Kyum; Kwon, Kwang-iI; Seo, Dae Bang; Lee, Sang Jun; Oh, Won Keun

doi:10.1016/j.bmcl.2010.05.067

Cited by 83 publications

(62 citation statements)

References 14 publications

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“…The mixture showed antiobesity effects against high-fat diet, but it caused no toxic response in mice (Nguyen et al, 2010). We also found that oral administration of 20 mg/kg nectandrin B in C57/BL6 mice for 6 weeks made no significant change in the organs of mice (data not shown).…”

Section: Discussionmentioning

confidence: 63%

“…The species M. fragrans has been used traditionally for spices and various medicinal purposes-as a stomachic, carminative, tonic, aphrodisiac, and nervous system stimulant (Nguyen et al, 2010). Several studies have shown that lignan compounds from M. fragrans have beneficial anti-inflammatory, anti-diabetes and antioxidant effects (Han et al, 2008a,b;Kwon et al, 2008;Ma et al, 2009;Anggakusuma et al, 2010).…”

Section: Discussionmentioning

confidence: 99%

“…It is known that phosphorylation of Ser1177 in eNOS, which plays an important role in the regulation of eNOS activity, is induced by AMPK and results in NO production in endothelial cells (Chen et al, 1999;Morrow et al, 2003). In our previous study, we reported that nectandrin B potently activates AMPK in differentiated skeletal muscle cells (Nguyen et al, 2010). Hence, we examined the effect of nectandrin B on AMPK activity in human endothelial cells.…”

Section: Effect Of Nectandrin B On Enos Phosphorylation 1171mentioning

confidence: 94%

“…However, the mechanisms underlying these activities have not been clarified. To address this gap in our knowledge, we isolated seven 2,5-bis-aryl-3,4-dimethyltetrahydrofuran lignans from total extracts of M. fragrans, and nectandrin B had a strong AMPK stimulation effect at a concentration of 5 M in differentiated C2C12 cells (Nguyen et al, 2010).…”

Section: Introductionmentioning

confidence: 99%

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Nectandrin B Activates Endothelial Nitric-Oxide Synthase Phosphorylation in Endothelial Cells: Role of the AMP-Activated Protein Kinase/Estrogen Receptor α/Phosphatidylinositol 3-kinase/Akt Pathway

Hien

Oh²,

Nguyen³

et al. 2011

Mol Pharmacol

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We revealed previously that nectandrin B isolated from Myristica fragrans (nutmeg, Myristicaceae) functions as a potent AMP-activated protein kinase (AMPK) activator and showed its antiobesity effect. In this study, we investigated whether nectandrin B affects phosphorylation of endothelial nitric-oxide synthase (eNOS) in human endothelial cells. Nectandrin B increased the phosphorylation of eNOS and nitric oxide (NO) production in a concentration-dependent manner and maximal effect was found at 10 g/ml. Nectandrin B activates AMPK, presumably via Ca 2ϩ /calmodulin kinase II activation and nectandrin B-stimulated eNOS phosphorylation was reversed by AMPK inhibition. Both the enzyme activity of phosphatidylinositol 3-kinase (PI3K) and the estrogen receptor (ER)-dependent reporter gene transcription were enhanced by nectandrin B. ER␣ inhibition by specific antagonist or small interfering siRNA (siRNA) suppressed nectandrin B-mediated eNOS phosphorylation. Moreover, AMPK inhibition significantly reversed the activation of ER-dependent transcription and PI3K activation in response to nectandrin B. Nectandrin B evoked endothelium-dependent relaxation in rat aortic rings, and this was blocked by inhibition of AMPK, ER, or PI3K. These results suggest that potent AMPK activator nectandrin B enhances NO production via eNOS phosphorylation in endothelial cells and ER␣-dependent PI3K activity is required.

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Section: Discussionmentioning

confidence: 63%

Section: Discussionmentioning

confidence: 99%

Section: Effect Of Nectandrin B On Enos Phosphorylation 1171mentioning

confidence: 94%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Nectandrin B Activates Endothelial Nitric-Oxide Synthase Phosphorylation in Endothelial Cells: Role of the AMP-Activated Protein Kinase/Estrogen Receptor α/Phosphatidylinositol 3-kinase/Akt Pathway

Hien

Oh²,

Nguyen³

et al. 2011

Mol Pharmacol

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“…In this regard and as part of our program to search for new AMPK activators with chemopreventive activity from plants, 12 we found that diarylbutane-type lignans from M. fragrans exhibited potential AMPK activation effects and strong growth inhibition activities against MCF-7 breast cancer cells. As major active principles, two diarylbutane-type lignans, macelignan (1) 13 and MDGA (2)…”

mentioning

confidence: 99%

Diarylbutane-type Lignans fromMyristica fragrans(Nutmeg) show the Cytotoxicity against Breast Cancer Cells through Activation of AMP-activated Protein Kinase

Nguyen

Choi

et al. 2017

Nat Prod Sci

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-In our program to search for new AMP-activated protein kinase (AMPK) activators from plants that exert potential anticancer property, we found that an EtOAc extract of Myristica fragrans (nutmeg) activated AMPK enzyme in human breast cancer MCF-7 cells. Two major diarylbutane-type lignans, macelignan and meso-dihydroguaiaretic acid (MDGA), were isolated as active principles from this extract. Treatment of breast cancer cells with two compounds induced cellular apoptosis, evidenced by cleavage of poly-(ADP-ribose) polymerase (PARP) and Ser 15 phosphorylation of p53. Moreover, macelignan and MDGA significantly inhibited the colony formation of MCF-7 breast cancer cells on soft agar. Intraperitoneal injection of macelignan and MDGA (20 mg/kg) suppressed the tumor growth of 4T1 mammary cancer cells. These results indicate that the chemopreventive effects of two major diarylbutane-type lignans from Myristica fragrans (nutmeg) may be associated with induction of apoptosis presumably through AMPK activation.

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Chemical Synthesis Enables the Configurational Determination of Myristriol, a Highly Oxygenated Phenylpropanoid from Myristica fragrans Houtt

Xiao

Zhang

Wang

et al. 2023

Chemistry & Biodiversity

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AMP-activated protein kinase (AMPK) activators from Myristica fragrans (nutmeg) and their anti-obesity effect

Cited by 83 publications

References 14 publications

Nectandrin B Activates Endothelial Nitric-Oxide Synthase Phosphorylation in Endothelial Cells: Role of the AMP-Activated Protein Kinase/Estrogen Receptor α/Phosphatidylinositol 3-kinase/Akt Pathway

Nectandrin B Activates Endothelial Nitric-Oxide Synthase Phosphorylation in Endothelial Cells: Role of the AMP-Activated Protein Kinase/Estrogen Receptor α/Phosphatidylinositol 3-kinase/Akt Pathway

Diarylbutane-type Lignans fromMyristica fragrans(Nutmeg) show the Cytotoxicity against Breast Cancer Cells through Activation of AMP-activated Protein Kinase

Chemical Synthesis Enables the Configurational Determination of Myristriol, a Highly Oxygenated Phenylpropanoid from Myristica fragrans Houtt

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