Metabolomic Profiling of Cellular Responses to Carvedilol Enantiomers in Vascular Smooth Muscle Cells

Wang, Mingxuan; Bai, Jing; Chen, Wei Ning; Ching, Chi Bun

doi:10.1371/journal.pone.0015441

Cited by 27 publications

(23 citation statements)

References 40 publications

(46 reference statements)

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“…The effect of green tea administration on obesity-related parameters has been reported by a number of human studies (Table 3) [56–76]. Green tea consumption, in the forms of EGCG or GTE with or without caffeine, by obese subjects decreased BW, body mass index (BMI), and waist and hip circumference, total body fat, and abdominal visceral and subcutaneous fat area.…”

Section: Epigallocatechin Gallate and Green Tea Extractmentioning

confidence: 95%

Novel insights of dietary polyphenols and obesity

Wang

Moustaid‐Moussa

Chen

et al. 2014

The Journal of Nutritional Biochemistry

775

575

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Prevalence of obesity has steadily increased over the past three decades both in the United States and worldwide. Recent studies have shown the role of dietary polyphenols in the prevention of obesity and obesity-related chronic diseases. Here we evaluated the impact of commonly consumed polyphenols, including green tea catechins and epigallocatechin gallates, resveratrol, and curcumin, on obesity and obesity-related-inflammation. Cellular studies demonstrated that these dietary polyphenols reduce viability of adipocytes and proliferation of preadipocytes, suppress adipocyte differentiation and triglyceride accumulation, stimulate lipolysis and fatty acid β-oxidation, and reduce inflammation. Concomitantly, the polyphenols modulate signaling pathways including the AMP-activated protein kinase, peroxisome proliferator activated receptor γ, CCAAT/enhancer binding protein α, PPAR gamma activator 1-alpha, sirtuin 1, sterol regulatory element binding protein-1c, uncoupling proteins 1 and 2, and nuclear factor kappa B that regulate adipogenesis, antioxidant and anti-inflammatory responses. Animal studies strongly suggest that commonly consumed polyphenols described in this review have a pronounced effect on obesity as shown by lower body weight, fat mass, and triglycerides through enhancing energy expenditure and fat utilization, and modulating glucose hemostasis. Limited human studies have been conducted in this area, and are inconsistent about the anti-obesity impact of dietary polyphenols, probably due to the various study designs and lengths, variation among subjects (age, gender, ethnicity), chemical forms of the dietary polyphenols used and confounding factors such as other weight reducing agents. Future randomized controlled trials are warranted to reconcile the discrepancies between preclinical efficacies and inconclusive clinic outcomes of these polyphenols.

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Section: Epigallocatechin Gallate and Green Tea Extractmentioning

confidence: 95%

Novel insights of dietary polyphenols and obesity

Wang

Moustaid‐Moussa

Chen

et al. 2014

The Journal of Nutritional Biochemistry

775

575

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“…Therefore, metabolic profiling of cells underlying treatment with drug candidates is greatly helpful for understanding their action mechanisms and aids in their further modifications. Currently, the metabolomic-based technology has been reported for the exploration of drug-cell interactions [26], [27] and action mechanisms of drugs [28]. However, a comprehensive metabolite profile of acridone derivatives against cell lines is still lacking.…”

Section: Introductionmentioning

confidence: 99%

Acridone Derivative 8a Induces Oxidative Stress-Mediated Apoptosis in CCRF-CEM Leukemia Cells: Application of Metabolomics in Mechanistic Studies of Antitumor Agents

et al. 2013

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A new acridone derivative, 2-aminoacetamido-10-(3, 5-dimethoxy)-benzyl-9(10H)-acridone hydrochloride (named 8a) synthesized in our lab shows potent antitumor activity, but the mechanism of action remains unclear. Herein, we report the use of an UPLC/Q-TOF MS metabolomic approach to study the effects of three compounds with structures optimized step-by-step, 9(10H)-acridone (A), 10-(3,5-dimethoxy)benzyl-9(10H)-acridone (I), and 8a, on CCRF-CEM leukemia cells and to shed new light on the probable antitumor mechanism of 8a. Acquired data were processed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA) to identify potential biomarkers. Comparing 8a-treated CCRF-CEM leukemia cells with vehicle control (DMSO), 23 distinct metabolites involved in five metabolic pathways were identified. Metabolites from glutathione (GSH) and glycerophospholipid metabolism were investigated in detail, and results showed that GSH level and the reduced/oxidized glutathione (GSH/GSSG) ratio were significantly decreased in 8a-treated cells, while L-cysteinyl-glycine (L-Cys-Gly) and glutamate were greatly increased. In glycerophospholipid metabolism, cell membrane components phosphatidylcholines (PCs) were decreased in 8a-treated cells, while the oxidative products lysophosphatidylcholines (LPCs) were significantly increased. We further found that in 8a-treated cells, the reactive oxygen species (ROS) and lipid peroxidation product malondialdehyde (MDA) were notably increased, accompanied with decrease of mitochondrial transmembrane potential, release of cytochrome C and activation of caspase-3. Taken together our results suggest that the acridone derivative 8a induces oxidative stress-mediated apoptosis in CCRF-CEM leukemia cells. The UPLC/Q-TOF MS based metabolomic approach provides novel insights into the mechanistic studies of antitumor drugs from a point distinct from traditional biological investigations.

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“…The sample for metabolic profiling was derivatized according to previous work [188]. For metabolic profiling, the same GC…”

Section: Metabolic Profilingmentioning

confidence: 99%

Fatty acids as biofuel precursors accumulation : an investigation by metabolic engineering approach

Chen¹

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Metabolomic Profiling of Cellular Responses to Carvedilol Enantiomers in Vascular Smooth Muscle Cells

Cited by 27 publications

References 40 publications

Novel insights of dietary polyphenols and obesity

Novel insights of dietary polyphenols and obesity

Acridone Derivative 8a Induces Oxidative Stress-Mediated Apoptosis in CCRF-CEM Leukemia Cells: Application of Metabolomics in Mechanistic Studies of Antitumor Agents

Fatty acids as biofuel precursors accumulation : an investigation by metabolic engineering approach

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