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, Tran Thi; Oh, Won Keun; Nguyen, Phi Hung; Oh, Seok Jeong; Lee, Moo Yeol; Kang, Keon Wook

doi:10.1124/mol.111.073502

Cited by 19 publications

(10 citation statements)

References 53 publications

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“…Because the expression of P-Ser 15 -p53, a substrate of AMPK, was increased in old HDFs, and NecB was shown to stimulate the AMPK-related pathways in differentiated C2C12 cells [27–29], the expression and phosphorylation status of AMPK were examined in HDFs. After treatment with vehicle, an AMPK activator AICAR (positive control), an AMPK inhibitor compound C (negative control), or 10−20 μg/mL NecB for 2 days, the protein levels in cell lysates were examined by western blot analysis for AMPK phosphorylation on Thr 172 (P-Thr 172 -AMPK; an activated form of AMPK) and total AMPK, using glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal control.…”

Section: Resultsmentioning

confidence: 99%

“…Previously, NecB was suggested as an AMPK activator in various cell types, including human HDFs [27], hepatocytes [33], rat VSMCs [29], and differentiated C2C12 cells [28]. It was also shown that the activation capacity of AMPK declines during aging [13].…”

Section: Discussionmentioning

confidence: 99%

“…Myristica fragrans (nutmeg), an aromatic evergreen tree cultivated in India, South Africa, and other tropical countries, has been used in food and is a source of spices. Nutmeg extract and its active constituents, tetrahydrofuroguaiacin B, nectandrin A (Nec A), and nectandrin B (NecB), have been suggested for use in the treatment of obesity, type-2 diabetes, and other metabolic disorders, presumably via AMPK activation in animal model [27]. Therefore, in this study, NecB was selected as a candidate for preventing aging and age-related diseases.…”

Section: Introductionmentioning

confidence: 99%

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Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels

Jang

Yang

et al. 2019

Aging

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Nectandrin B (NecB) is a bioactive lignan compound isolated from Myristica fragrans (nutmeg), which functions as an activator of AMP-activated protein kinase (AMPK). Because we recently found that treatment with NecB increased the cell viability of old human diploid fibroblasts (HDFs), the underlying molecular mechanism was investigated. NecB treatment in old HDFs reduced the activity staining of senescence-associated β-galactosidase and the levels of senescence markers, such as the Ser 15 phosphorylated p53, caveolin-1, p21 waf1 , p16 ink4a , p27 kip1 , and cyclin D1. NecB treatment increased that in S phase, indicating a enhancement of cell cycle entry. Interestingly, NecB treatment ameliorated age-dependent activation of AMPK in old HDFs. Moreover, NecB reversed the age-dependent expression and/or activity changes of certain sirtuins (SIRT1−5), and cell survival/death-related proteins. The transcriptional activity of Yin-Yang 1 and the expression of downstream proteins were elevated in NecB-treated old HDFs. In addition, NecB treatment exerted a radical scavenging effect in vitro , reduced cellular ROS levels, and increased antioxidant enzymes in old HDFs. Moreover, NecB-mediated activation of the AMPK pathway reduced intracellular ROS levels. These results suggest that NecB-induced protection against cellular senescence is mediated by ROS-scavenging through activation of AMPK. NecB might be useful in ameliorating age-related diseases and extending human lifespan.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels

Jang

Yang

et al. 2019

Aging

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“…DAF-2 DA interacts with NO and NO-derived nitrosating species to produce a fluorescent by-product [19], which can be used as an indicator of NO synthesis in living cells [20]. This method has been used successfully in endothelial cells [21] and has been adapted herein for use in C2C12 cells.…”

Section: Resultsmentioning

confidence: 99%

Neuronal nitric oxide synthase is phosphorylated in response to insulin stimulation in skeletal muscle

Hinchee-Rodriguez

Garg

Venkatakrishnan

et al. 2013

Biochemical and Biophysical Research Communications

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Type 2 Diabetes (T2DM) is the seventh leading cause of death in the United States, and is quickly becoming a global pandemic. T2DM results from reduced insulin sensitivity coupled with a relative failure of insulin secretion. Reduced insulin sensitivity has been associated with reduced nitric oxide synthase (NOS) activity and impaired glucose uptake in T2DM skeletal muscle. Upon insulin stimulation, NO synthesis increases in normal adult skeletal muscle, whereas no such increase is observed in T2DM adults. Endothelial NOS is activated by phosphorylation in the C-terminal tail in response to insulin. Neuronal NOS (nNOS), the primary NOS isoform in skeletal muscle, contains a homologous phosphorylation site, raising the possibility that nNOS, too, may undergo an activating phosphorylation event upon insulin treatment. Yet it remains unknown if or how nNOS is regulated by insulin in skeletal muscle. Data shown herein indicate that nNOS is phosphorylated in response to insulin in skeletal muscle and that this phosphorylation event occurs rapidly in C2C12 myotubes, resulting in increased NO production. In vivo phosphorylation of nNOS was also observed in response to insulin in mouse skeletal muscle. These results indicate, for the first time, that nNOS is phosphorylated in skeletal muscle in response to insulin and in association with increased NO production.

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“…Pathogenic factors cannot enter the lower layer of intestinal mucosa. As a commonly used drug, SSP is composed of many active components, such as evodiamine, schizandrin A, myrislignan, and macelignan, which have a wide range of pharmacological effects, including anti-inflammation, antitumor, anti-free radicals, and regulating immunity [38][39][40]. Numerous studies have shown that myrislignan protects skin keratinocytes from ultraviolet B-induced damage and reduces the activation of MAPK and PI3K/Akt [41].…”

Section: Discussionmentioning

confidence: 99%

Sishen Pill Maintained Colonic Mucosal Barrier Integrity to Treat Ulcerative Colitis via Rho/ROCK Signaling Pathway

Zhang

Zhao

Liu

et al. 2021

Evidence-Based Complementary and Alternative Medicine

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Sishen Pill (SSP) is a classical prescription of traditional Chinese medicine and often used to treat gastrointestinal diseases, including ulcerative colitis (UC). However, its mechanism is still unclear. We aimed to determine the mechanism of SSP in the treatment of UC by investigating if it maintains the integrity of the intestinal mucosal barrier via the Rho A/Rho kinase (ROCK) signaling pathway. Administration of 2,4,6-trinitrobenzene sulfonic acid (TNBS) successfully induced chronic UC in rats, while the treatment effect of SSP was evaluated by body weight change, colonic length, colonic weight, colonic weight index, histological injury score, and pathological injury score after colitis rats were treated for 7 days. TNF-α and IL-1β levels were analyzed by ELISA, and the proteins of PI3K/Akt and RhoA/ROCK signaling pathway and junction proteins expression were measured by western blotting assay, and the distribution of Claudin 5 was shown by immunofluorescence. SSP significantly improved the clinical symptoms of colitis in rats and reduced the expression of p-RhoA, ROCK1, PI3K, and Akt in the colon mucosa, while it increased the expression of p-Rac and related proteins (Claudin-5, JAM1, VE-cadherin, and Connexin 43). In addition, SSP increased p-AMPKα and PTEN proteins expression, decreased Notch1 level, and hinted that activation of the PI3K/Akt signaling pathway was inhibited. In conclusion, SSP effectively treated chronic colitis induced by TNBS, which may have been achieved by inhibiting PI3K/Akt signal to suppress activation of the Rho/ROCK signaling pathway to finally maintain the integrity of the intestinal mucosal barrier.

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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

Cited by 19 publications

References 53 publications

Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels

Nectandrin B-mediated activation of the AMPK pathway prevents cellular senescence in human diploid fibroblasts by reducing intracellular ROS levels

Neuronal nitric oxide synthase is phosphorylated in response to insulin stimulation in skeletal muscle

Sishen Pill Maintained Colonic Mucosal Barrier Integrity to Treat Ulcerative Colitis via Rho/ROCK Signaling Pathway

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