N,N-Dimethlyacetamide Prevents the High-Fat Diet-Induced Increase in Body Weight

Bhattacharya, Indranil; Ghayor, Chafik; Domínguez, Ana Pérez; Weber, Franz E.

doi:10.3389/fphar.2019.01274

Cited by 4 publications

(4 citation statements)

References 32 publications

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“…Ghayor et al have shown that DMA prevents osteoporosis in rats via the inhibition of osteoclast mediated bone resorption [23] and enhances bone regeneration impaired by excess in ammation [24]. In other re-purposing studies, DMA has been shown to prevent high-fat diet induced weight gain [25] and has been investigated as a potential reversible contraceptive [26]. Ghayor et al's observation that DMA acts by inhibiting NF-kB is consistent with our ndings [21][22][23].…”

Section: Introductionsupporting

confidence: 90%

FDA-Approved Excipient N,N-Dimethylacetamide Attenuates Inflammatory Bowel Disease in In-Vitro and In-Vivo Models

Koya¹,

Shen

et al. 2021

Preprint

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Inflammatory bowel disease (IBD) affects almost 7 million people worldwide and is increasing in incidence. While the precise pathogenesis of IBD remains unknown, the production of inflammatory cytokines and chemokines play a central role. We have previously found that N,N-dimethylacetamide (DMA), a widely used non-toxic drug excipient, suppresses cytokine and chemokine secretion in vitro and prevents inflammation-induced preterm birth in vivo. Using sandwich enzyme-linked immunosorbent assays (ELISAs), we tested whether DMA attenuates cytokine and chemokine secretion from LPS- or TNFa-stimulated human intestinal epithelial cells and human monocytes and HMGB1 release from RAW 264.7 cells. To test our hypothesis that the mechanism of DMA’s effects in in-vitro and in-vivo models of IBD is inhibition of the NF-kB pathway, we used western blotting to track levels of the nuclear factor kappa B (NF-kB) inhibitory molecule I kappa B alpha (IkBa) in THP-1 human monocytes in the absence or presence of DMA. Finally, we induced colitis in C57Bl/6 mice with dextran sodium sulfate (DSS) and then tested whether daily i.p injections of DMA at 2.1 g/kg/day attenuates clinical and histopathologic signs of colitis. DMA attenuated cytokine and chemokine release from human intestinal epithelial cells and human monocytes and HMGB1 release from RAW 264.7 cells. Importantly, DMA prevented degradation of IkBa in THP-1 cells, thereby suggesting one mechanism for DMA’s effects. Finally, we show here, for the first time, that DMA attenuates clinical and histologic features of DSS-induced colitis. Based on these data, DMA should be further explored in preclinical and clinical trials for its potential as novel drug therapy for IBD.

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Section: Introductionsupporting

confidence: 90%

FDA-Approved Excipient N,N-Dimethylacetamide Attenuates Inflammatory Bowel Disease in In-Vitro and In-Vivo Models

Koya¹,

Shen

et al. 2021

Preprint

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“…Previous studies have shown that N,N-dimethylacetamide (DMA), a common organic solvent and FDA approved drug excipient, significantly inhibits inflammatory responses in in-vivo models of preterm birth 36 , inflammatory bowel disease 37 , osteoporosis 38 and obesity 39 via inhibition of the NF-κB signaling pathway 29 . DMA is a small molecule with a molecular weight of 87 g/mol, which can easily penetrate the blood–brain barrier 40 , 41 .…”

Section: Introductionmentioning

confidence: 99%

N,N-dimethylacetamide targets neuroinflammation in Alzheimer’s disease in in-vitro and ex-vivo models

Wei

Koya

Acharekar

et al. 2023

Sci Rep

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Alzheimer’s disease (AD) is a chronic degenerative brain disorder with no clear pathogenesis or effective cure, accounting for 60–80% of cases of dementia. In recent years, the importance of neuroinflammation in the pathogenesis of AD and other neurodegenerative disorders has come into focus. Previously, we made the serendipitous discovery that the widely used drug excipient N,N-dimethylacetamide (DMA) attenuates endotoxin-induced inflammatory responses in vivo. In the current work, we investigate the effect of DMA on neuroinflammation and its mechanism of action in in-vitro and ex-vivo models of AD. We show that DMA significantly suppresses the production of inflammatory mediators, such as reactive oxygen species (ROS), nitric oxide (NO) and various cytokines and chemokines, as well as amyloid-β (Aβ), in cultured microglia and organotypic hippocampal slices induced by lipopolysaccharide (LPS). We also demonstrate that DMA inhibits Aβ-induced inflammation. Finally, we show that the mechanism of DMA’s effect on neuroinflammation is inhibition of the nuclear factor kappa-B (NF-κB) signaling pathway and we show how DMA dismantles the positive feedback loop between NF-κB and Aβ synthesis. Taken together, our findings suggest that DMA, a generally regarded as safe compound that crosses the blood brain barrier, should be further investigated as a potential therapy for Alzheimer’s disease and neuroinflammatory disorders.

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“…These intracellular events lead to activation of the inhibitor kappa B kinase (IKK), resulting in phosphorylation of inhibitor kappa B (IκB) and its subsequent degradation by the proteasome. Degradation of IκB leads to release of NF-κB dimers (prototypically p65/p50 subunits), their translocation into the nucleus and their binding to consensus sequences of neuronal gene targets like amyloid-beta precursor protein (APP) (Pekson et Previous studies have shown that N,N-dimethylacetamide (DMA), a common organic solvent and FDA approved drug excipient, signi cantly inhibits in ammatory responses in in-vivo models of preterm birth (Sundaram et al 2013), in ammatory bowel disease (Koya et al 2022), osteoporosis (Ghayor et al 2017) and obesity (Bhattacharya et al 2019) via inhibition of the NF-κB signaling pathway (Pekson et al 2016).…”

Section: Introductionmentioning

confidence: 99%

N,N-Dimethylacetamide Targets Neuroinflammation in Alzheimer’s Disease in In-vitro and Ex-vivo Models

Wei¹,

Koya²,

Acharekar³

et al. 2022

Preprint

View full text Add to dashboard Cite

Alzheimer’s disease (AD) is a chronic degenerative brain disorder with no clear pathogenesis or effective cure, accounting for 60–80% cases of dementia. In recent years, the importance of neuroinflammation in the pathogenesis of AD and other neurodegenerative disorders has come into focus. Previously, we made the serendipitous discovery that the widely used drug excipient N,N-dimethylacetamide (DMA) attenuates endotoxin-induced inflammatory responses in vivo. In the current work, we investigate the effect of DMA on neuroinflammation and its mechanism of action in in-vitro and ex-vivo models of AD. We show that DMA significantly suppresses the production of inflammatory mediators, such as reactive oxygen species (ROS), nitric oxide (NO) and various cytokines and chemokines, as well as amyloid-β (Aβ), in cultured microglia and organotypic hippocampal slices induced by lipopolysaccharide (LPS). We also demonstrate that DMA inhibits Aβ-induced inflammation. Finally, we show that the mechanism of DMA’s effect on neuroinflammation is inhibition of the nuclear factor kappa-B (NF-κB) signaling pathway and we show how DMA dismantles the positive feedback loop between NF-κB and Ab synthesis. Taken together, our findings suggest that DMA, a generally regarded as safe compound that crosses the blood brain barrier, should be further investigated as a potential therapy for Alzheimer’s disease and neuroinflammatory disorders.

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N,N-Dimethlyacetamide Prevents the High-Fat Diet-Induced Increase in Body Weight

Cited by 4 publications

References 32 publications

FDA-Approved Excipient N,N-Dimethylacetamide Attenuates Inflammatory Bowel Disease in In-Vitro and In-Vivo Models

FDA-Approved Excipient N,N-Dimethylacetamide Attenuates Inflammatory Bowel Disease in In-Vitro and In-Vivo Models

N,N-dimethylacetamide targets neuroinflammation in Alzheimer’s disease in in-vitro and ex-vivo models

N,N-Dimethylacetamide Targets Neuroinflammation in Alzheimer’s Disease in In-vitro and Ex-vivo Models

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