scholarly journals Antimetabolic Syndrome Effect of Phytosome Containing the Combined Extracts of Mulberry and Ginger in an Animal Model of Metabolic Syndrome

2019 ◽  
Vol 2019 ◽  
pp. 1-19 ◽  
Author(s):  
Nut Palachai ◽  
Jintanaporn Wattanathorn ◽  
Supaporn Muchimapura ◽  
Wipawee Thukham-mee
Keyword(s):  
Oxidative Stress ◽  
Animal Model ◽  
Adipose Tissue ◽  
Body Weight Gain ◽  
Biological Activities ◽  
Health Benefit ◽  
Underlying Mechanism ◽  
Metabolic Parameter ◽  
Oxidative Stress Status

Due to the antimetabolic syndrome effect of mulberry and ginger together with the advantages of the synergistic effect and phytosome encapsulation technique, we hypothesized that phytosome containing the combined extracts of mulberry and ginger (PMG) should be able to manage MetS. PMG was developed and assessed the phenolic content and biological activities associated with the pathophysiology of MetS. The antimetabolic syndrome effect and the possible underlying mechanisms in the animal model of MetS were also assessed. Male Wistar rats induced MetS by subjecting to a 16-week high-carbohydrate high-fat diet. MetS rats were orally given PMG at doses of 50, 100, and 200 mg/kg for 21 days. They were determined metabolic parameter changes in serum, histomorphology changes of adipose tissue, the inflammatory cytokines such as IL-6 and TNF-α, oxidative stress status, PPAR-γ, and HDAC3 in adipose tissue. Our in vitro data showed that PMG increased phenolic contents and biological activities. PMG significantly improved MetS parameters including body weight gain, lipid profiles, plasma glucose, HOMA-IR, and ACE. In addition, the density and size of adipocyte, adiposity index, and weights of adipose tissues were also improved. Moreover, the decrease in TNF-α and IL-6, oxidative stress status, and HDAC3 expression together with the increase in PPAR-γ expression in adipose tissue was also observed. These data suggest that PMG exhibit antimetabolic syndrome and the possible underlying mechanism may be associated partly with the modulation effect on HDAC3, PPAR-γ, and adipose tissue. In addition, PMG also improves oxidative stress and inflammation in MetS. Therefore, PMG can be served as the potential supplement to manage MetS. However, a clinical trial study is essential to confirm this health benefit.

Action of Thioglycosides of 1,2,4-Triazoles and Imidazoles on the Oxidative Stress and Glycosidases in Mice with Molecular Docking

2019 ◽  
Vol 16 (6) ◽  
pp. 696-710
Author(s):  
Mahmoud Balbaa ◽  
Doaa Awad ◽  
Ahmad Abd Elaal ◽  
Shimaa Mahsoub ◽  
Mayssaa Moharram ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Molecular Docking ◽  
Active Sites ◽  
Biological Activities ◽  
Imidazole Ring ◽  
Quantitative Structure Activity Relationship ◽  
Binding Interaction ◽  
Qsar Study

Background: ,2,3-Triazoles and imidazoles are important five-membered heterocyclic scaffolds due to their extensive biological activities. These products have been an area of growing interest to many researchers around the world because of their enormous pharmaceutical scope. Methods: The in vivo and in vitro enzyme inhibition of some thioglycosides encompassing 1,2,4- triazole N1, N2, and N3 and/or imidazole moieties N4, N5, and N6. The effect on the antioxidant enzymes (superoxide dismutase, glutathione S-transferase, glutathione peroxidase and catalase) was investigated as well as their effect on α-glucosidase and β-glucuronidase. Molecular docking studies were carried out to investigate the mode of the binding interaction of the compounds with α- glucosidase and β -glucuronidase. In addition, quantitative structure-activity relationship (QSAR) investigation was applied to find out the correlation between toxicity and physicochemical properties. Results: The decrease of the antioxidant status was revealed by the in vivo effect of the tested compounds. Furthermore, the in vivo and in vitro inhibitory effects of the tested compounds were clearly pronounced on α-glucosidase, but not β-glucuronidase. The IC50 and Ki values revealed that the thioglycoside - based 1,2,4-triazole N3 possesses a high inhibitory action. In addition, the in vitro studies demonstrated that the whole tested 1,2,4-triazole are potent inhibitors with a Ki magnitude of 10-6 and exhibited a competitive type inhibition. On the other hand, the thioglycosides - based imidazole ring showed an antioxidant activity and exerted a slight in vivo stimulation of α-glucosidase and β- glucuronidase. Molecular docking proved that the compounds exhibited binding affinity with the active sites of α -glucosidase and β-glucuronidase (docking score ranged from -2.320 to -4.370 kcal/mol). Furthermore, QSAR study revealed that the HBD and RB were found to have an overall significant correlation with the toxicity. Conclusion: These data suggest that the inhibition of α-glucosidase is accompanied by an oxidative stress action.

scholarly journals Histone Carbonylation Is a Redox-Regulated Epigenomic Mark That Accumulates with Obesity and Aging

Antioxidants ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 1210
Author(s):  
Amy K. Hauck ◽  
Tong Zhou ◽  
Ambuj Upadhyay ◽  
Yuxiang Sun ◽  
Michael B. O’Connor ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Disease ◽  
Adipose Tissue ◽  
Fat Depots ◽  
Michael Adducts ◽  
Lipid Aldehydes ◽  
Visceral Adipose ◽  
Fat Feeding

Oxidative stress is a hallmark of metabolic disease, though the mechanisms that define this link are not fully understood. Irreversible modification of proteins by reactive lipid aldehydes (protein carbonylation) is a major consequence of oxidative stress in adipose tissue and the substrates and specificity of this modification are largely unexplored. Here we show that histones are avidly modified by 4-hydroxynonenal (4-HNE) in vitro and in vivo. Carbonylation of histones by 4-HNE increased with age in male flies and visceral fat depots of mice and was potentiated in genetic (ob/ob) and high-fat feeding models of obesity. Proteomic evaluation of in vitro 4-HNE- modified histones led to the identification of both Michael and Schiff base adducts. In contrast, mapping of sites in vivo from obese mice exclusively revealed Michael adducts. In total, we identified 11 sites of 4-hydroxy hexenal (4-HHE) and 10 sites of 4-HNE histone modification in visceral adipose tissue. In summary, these results characterize adipose histone carbonylation as a redox-linked epigenomic mark associated with metabolic disease and aging.

Abstract 3672: Loss of Perivascular Adipocyte Paracrine Function Leads to Increased Vascular Tone and Glucose Intolerance in Hypertension

Circulation ◽  
2008 ◽  
Vol 118 (suppl_18) ◽  
Author(s):  
Kaivan Khavandi ◽  
Adam Greenstein ◽  
Sarah Withers ◽  
Kazuhiko Sonoyama ◽  
Sarah Lewis ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Vascular Tone ◽  
Tnf Alpha ◽  
Perivascular Adipose Tissue ◽  
The Metabolic Syndrome ◽  
Adipocyte Cell ◽  
Therapeutic Opportunity

In order to investigate the contribution of perivascular adipose tissue (PVAT) to arterial function, a total of 55 small arteries harvested from 35 skin biopsies of patients with Metabolic Syndrome and matched controls were mounted as ring preparations in a wire myograph. Contractility to cumulative doses of Norepinephrine in the presence or absence of PVAT showed an anticontractile effect in arteries from healthy volunteers (p=0.009), which was lost in patients with Metabolic Syndrome. Bioassay studies confirmed that PVAT releases a hydrophilic anticontractile factor in health, which is absent in obesity. Using a soluble fragment of the human Type 1 receptor, we identified that the anticontractile factor was adiponectin, which is the sole mediator of vasodilation, acting by increasing endothelial bioavailability of nitric oxide. Significant endothelial dysfunction was observed in patients with Metabolic Syndrome (p<0.001). Quantitative image analysis of adipose tissue revealed significantly increased adipocyte cell size in patients with Metabolic Syndrome, compared with healthy controls (p<0.006). There was immunohistochemical evidence of inflammation with upregulation of TNF-alpha receptor 1 in these patients (p<0.001). Application of exogenous TNF-alpha abolished the anticontractile effect of PVAT by reducing adiponectin bioavailability. Oxidative stress also induced by cytokines TNF-alpha and IL-6 but not IL-1, reduced adiponectin production from PVAT and increased basal tone. When the obese microenvironment was replicated in vitro by inflicting hypoxia on PVAT, adiponectin activity was lost but then rescued by incubation with cytokine antagonists. Further application of the adiponectin receptor fragment abolished PVAT relaxation. We conclude that in healthy arteries, PVAT releases adiponectin which reduces vascular tone. In obesity, this is lost by a cascade of adipocyte hypertrophy, hypoxia, inflammation and oxidative stress. The resulting vasoconstriction contributes to hypertension, hypertriglyceridaemia and insulin resistance. Direct targeting of adiponectin release from PVAT therefore provides a novel therapeutic opportunity in the Metabolic Syndrome.

scholarly journals Encapsulated Mulberry Fruit Extract Alleviates Changes in an Animal Model of Menopause with Metabolic Syndrome

2019 ◽  
Vol 2019 ◽  
pp. 1-23 ◽  
Author(s):  
Jintanaporn Wattanathorn ◽  
Supannika Kawvised ◽  
Wipawee Thukham-mee
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Body Weight ◽  
Weight Gain ◽  
Protein Expression ◽  
Body Weight Gain ◽  
Atherogenic Index ◽  
Fruit Extract ◽  
Mulberry Fruit ◽  
Oxidative Stress Status

Currently, the therapeutic strategy against metabolic syndrome and its complications is required due to the increasing prevalence and its impact. Due to the benefits of both mulberry fruit extract and encapsulation technology, we hypothesized that encapsulated mulberry fruit extract (MME) could improve metabolic parameters and its complication risk in postmenopausal metabolic syndrome. To test this hypothesis, female Wistar rats were induced experimental menopause with metabolic syndrome by bilateral ovariectomy (OVX) and high-carbohydrate high-fat (HCHF) diet. Then, they were orally given MME at doses of 10, 50, and 250 mg/kg BW for 8 weeks and the parameters, such as percentage of body weight gain, total cholesterol, triglycerides, HDL-C, LDL-C, atherogenic index, fasting blood glucose, plasma glucose area under the curve, serum angiotensin-converting enzyme (ACE), oxidative stress status, histology, and protein expression of PPAR-γ, TNF-α, and NF-κB in adipose tissues were determined. MME improved body weight gain, adiposity index, glucose intolerance, lipid profiles, atherogenic index, ACE, oxidative stress status, and protein expression of TNF-αand NF-κB. Moreover, MME attenuated adipocyte hypertrophy and enhanced PPAR-γexpression. Taken altogether, MME decreased metabolic syndrome and its complication via the increased PPAR-γexpression. Therefore, MME is the potential candidate for improving metabolic syndrome and its related complications. However, further research in clinical trial is still necessary.

scholarly journals Mesenchymal Stem Cell Secretome Enhancement by Nicotinamide and Vasoactive Intestinal Peptide: A New Therapeutic Approach for Retinal Degenerative Diseases

2020 ◽  
Vol 2020 ◽  
pp. 1-14
Author(s):  
Maria L. Alonso-Alonso ◽  
Girish K. Srivastava ◽  
Ricardo Usategui-Martín ◽  
Maria T. García-Gutierrez ◽  
José Carlos Pastor ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vasoactive Intestinal Peptide ◽  
Cell Activation ◽  
Pigment Epithelium ◽  
Retinal Pigment ◽  
Glial Cell Activation ◽  
Oxidative Stress Status ◽  
Experimental Approaches ◽  
Exogenous Factors

Mesenchymal stem cells (MSC) secrete neuroprotective molecules that may be useful as an alternative to cell transplantation itself. Our purpose was to develop different pharmaceutical compositions based on conditioned medium (CM) of adipose MSC (aMSC) stimulated by and/or combined with nicotinamide (NIC), vasoactive intestinal peptide (VIP), or both factors; and to evaluate in vitro their proliferative and neuroprotective potential. Nine pharmaceutical compositions were developed from 3 experimental approaches: (1) unstimulated aMSC-CM collected and combined with NIC, VIP, or both factors (NIC+VIP), referred to as the aMSC-CM combined composition; (2) aMSC-CM collected just after stimulation with the mentioned factors and containing them, referred to as the aMSC-CM stimulated-combined composition; and (3) aMSC-CM previously stimulated with the factors, referred to as the aMSC stimulated composition. The potential of the pharmaceutical compositions to increase cell proliferation under oxidative stress and neuroprotection were evaluated in vitro by using a subacute oxidative stress model of retinal pigment epithelium cells (line ARPE-19) and spontaneous degenerative neuroretina model. Results showed that oxidatively stressed ARPE-19 cells exposed to aMSC-CM stimulated and stimulated-combined with NIC or NIC+VIP tended to have better recovery from the oxidative stress status. Neuroretinal explants cultured with aMSC-CM stimulated-combined with NIC+VIP had better preservation of the neuroretinal morphology, mainly photoreceptors, and a lower degree of glial cell activation. In conclusion, aMSC-CM stimulated-combined with NIC+VIP contributed to improving the proliferative and neuroprotective properties of the aMSC secretome. Further studies are necessary to evaluate higher concentrations of the drugs and to characterize specifically the aMSC-secreted factors related to neuroprotection. However, this study supports the possibility of improving the potential of new effective pharmaceutical compositions based on the secretome of MSC plus exogenous factors or drugs without the need to inject cells into the eye, which can be very useful in retinal pathologies.

scholarly journals The Role of Berberine in the Prevention of HIF-1α Activation to Alleviate Adipose Tissue Fibrosis in High-Fat-Diet-Induced Obese Mice

2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Meilin Hu ◽  
Fan Wu ◽  
Jinlong Luo ◽  
Jing Gong ◽  
Ke Fang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Body Weight Gain ◽  
Chinese Herb ◽  
Underlying Mechanism ◽  
The Body ◽  
Epididymal Adipose Tissue ◽  
Metabolic Dysfunction ◽  
High Fat ◽  
Tissue Fibrosis

Berberine (BBR) is the main active ingredient of a traditional Chinese herb Coptis chinensis. It has been reported to exhibit beneficial effects in treating diabetes and obesity. However, the underlying mechanism has not been fully elucidated. Adipose tissue fibrosis is a hallmark of obesity-associated adipose tissue dysfunction. HIF-1α plays a key role in adipose tissue fibrosis, which closely linked to metabolic dysfunction in obese state. We hypothesized that BBR may alleviate obesity-induced adipose tissue fibrosis and associated metabolic dysfunction through inhibition of HIF-1α. To test this hypothesis, we treated high fat diet (HFD) feeding mice with different dose of BBR (100 mg/kg, 200 mg/kg, and 300 mg/kg) for 8 weeks. We found that BBR treatment greatly decreased the body weight gain and reduced insulin resistance induced by HFD. Data also revealed that BBR improved histologic fibrous of epididymal white adipose tissue (eWAT) and was accompanied with inhibition of the abnormal synthesis and deposition of extracellular matrix (ECM) proteins, such as collagen and fibronectin. We also found that BBR treatment suppressed the expression of HIF-1α and decreased the mRNA expression of LOX in epididymal adipose tissue, which plays a key role in fibrosis development. Taken together, these results suggest that BBR can regulate metabolic homeostasis and suppress adipose tissue fibrosis through inhibiting the expression of HIF-1α.

scholarly journals Vitamin D alleviates oxidative stress in adipose tissue and mesenteric vessels from obese patients with subclinical inflammation

2020 ◽  
Vol 98 (2) ◽  
pp. 85-92 ◽  
Author(s):  
Mihaela Ionica ◽  
Oana M. Aburel ◽  
Adrian Vaduva ◽  
Alexandra Petrus ◽  
Sonia Rațiu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Vitamin D ◽  
Adipose Tissue ◽  
Vascular Function ◽  
Ex Vivo ◽  
Active Form ◽  
Reactive Oxygen Species Generation ◽  
Obese Patients ◽  
Tissue Samples

Obesity is an age-independent, lifestyle-triggered, pandemic disease associated with both endothelial and visceral adipose tissue (VAT) dysfunction leading to cardiometabolic complications mediated via increased oxidative stress and persistent chronic inflammation. The purpose of the present study was to assess the oxidative stress in VAT and vascular samples and the effect of in vitro administration of vitamin D. VAT and mesenteric artery branches were harvested during abdominal surgery performed on patients referred for general surgery (n = 30) that were randomized into two subgroups: nonobese and obese. Serum levels of C-reactive protein (CRP) and vitamin D were measured. Tissue samples were treated or not with the active form of vitamin D: 1,25(OH)2D3 (100 nmol/L, 12 h). The main findings are that in obese patients, (i) a low vitamin D status was associated with increased inflammatory markers and reactive oxygen species generation in VAT and vascular samples and (ii) in vitro incubation with vitamin D alleviated oxidative stress in VAT and vascular preparations and also improved the vascular function. We report here that the serum level of vitamin D is inversely correlated with the magnitude of oxidative stress in the adipose tissue. Ex vivo treatment with active vitamin D mitigated obesity-related oxidative stress.

scholarly journals Baru Pulp (Dipteryx alata Vogel): Fruit from the Brazilian Savanna Protects against Oxidative Stress and Increases the Life Expectancy of Caenorhabditis elegans via SOD-3 and DAF-16

Biomolecules ◽  
2020 ◽  
Vol 10 (8) ◽  
pp. 1106
Author(s):  
Natasha Rios Leite ◽  
Laura Costa Alves de Araújo ◽  
Paola dos Santos da Rocha ◽  
Danielle Araujo Agarrayua ◽  
Daiana Silva Ávila ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Caenorhabditis Elegans ◽  
Life Expectancy ◽  
Biological Activities ◽  
Radical Scavenging ◽  
Brazilian Savanna ◽  
Beneficial Effects ◽  
Dipteryx Alata

Fruits are sources of bioactive compounds that are responsible for several biological activities. Therefore, this study aimed to identify the chemical composition of the pulp of the Brazilian Savanna fruit Dipteryx alata; evaluate its toxic effects, influence on the life expectancy of the nematode Caenorhabditis elegans, and its antioxidant activities in vitro and in vivo; and describe the mechanisms involved. The chemical compounds identified include phenols, terpenes, fatty acid derivatives, vitamins, and a carboxylic acid. The in vitro antioxidant activity was demonstrated by radical scavenging methods. in vivo, the D. alata fruit pulp was not toxic and promoted resistance to oxidative stress in nematodes exposed to a chemical oxidizing agent. Furthermore, it promoted an increased life expectancy in wild-type nematodes and increased the expression of superoxide dismutase and the nuclear translocation of DAF-16. These results suggest that the beneficial effects identified are related to these two genes, which are involved in the regulation of metabolic activities, the control of oxidative stress, and the lifespan of C. elegans. These beneficial effects, which may be related to its chemical constituents, demonstrate its potential use as a functional and/or nutraceutical food.

scholarly journals In vitro assessment of the cytotoxic, genotoxic and oxidative stress effects of the synthetic cannabinoid JWH-018 in human SH-SY5Y neuronal cells

2020 ◽  
Vol 9 (6) ◽  
pp. 734-740
Author(s):  
Yigit Sezer ◽  
Ayse Tarbin Jannuzzi ◽  
Marilyn A Huestis ◽  
Buket Alpertunga
Keyword(s):  
Oxidative Stress ◽  
Neuronal Cells ◽  
Underlying Mechanism ◽  
Synthetic Cannabinoid ◽  
Stress Effects ◽  
Legal High ◽  
New Generation ◽  
And Oxidative Stress

Abstract Background: JWH-018 was the first synthetic cannabinoid introduced as a legal high and the first of the new generation of novel psychoactive substances that flooded worldwide drug markets. JWH-018 was marketed as “spice,” “herbal incense,” or “herbal blend,” as a popular and legal (at the time) alternative to cannabis (marijuana). JWH-018 is a potent synthetic cannabinoid with considerable toxicity associated with its use. JWH-018 has qualitatively similar but quantitatively greater pharmacological effects than cannabis, leading to intoxications and even deaths. The mechanisms of action of the drug’s toxicity require research, and thus, the aim of the present study was to investigate the toxicological profile of JWH-018 in human SH-SY5Y neuronal cells. Methods: SH-SY5Y neuronal cells were exposed to increasing concentrations from 5 to 150 μM JWH-018 over 24 h. Cytotoxicity, DNA damage, the apoptotic/necrotic rate, and oxidative stress were assessed following SH-SY5Y exposure. Results: JWH-018 did not produce a significant decrease in SH-SY5Y cell viability, did not alter apoptotic/necrotic rate, and did not cause genotoxicity in SH-SY5Y cells with 24-h exposure. Glutathione reductase and catalase activities were significantly reduced; however, there was no significant change in glutathione peroxidase activity. Also, JWH-018 treatment significantly decreased glutathione concentrations, significantly increased protein carbonylation, and significantly increased malondialdehyde (MDA) concentrations. For significance, all P &lt; 0.05. Discussion/Conclusion: JWH-018 produced oxidative stress in SH-SY5Y cells that could be an underlying mechanism of JWH-018 neurotoxicity. Additional in vivo animal and human-based studies are needed to confirm our findings.

scholarly journals Inhibition of Oxidative Neurotoxicity and Scopolamine-Induced Memory Impairment by γ-Mangostin: In Vitro and In Vivo Evidence

2019 ◽  
Vol 2019 ◽  
pp. 1-14 ◽  
Author(s):  
Youngmun Lee ◽  
Sunyoung Kim ◽  
Yeonsoo Oh ◽  
Young-Mi Kim ◽  
Young-Won Chin ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Memory Impairment ◽  
Neuronal Damage ◽  
Biological Activities ◽  
Neuronal Cell Death ◽  
Neuronal Cell ◽  
Ros Generation ◽  
Garcinia Mangostana

Among a series of xanthones identified from mangosteen, the fruit of Garcinia mangostana L. (Guttifereae), α- and γ-mangostins are known to be major constituents exhibiting diverse biological activities. However, the effects of γ-mangostin on oxidative neurotoxicity and impaired memory are yet to be elucidated. In the present study, the protective effect of γ-mangostin on oxidative stress-induced neuronal cell death and its underlying action mechanism(s) were investigated and compared to that of α-mangostin using primary cultured rat cortical cells. In addition, the effect of orally administered γ-mangostin on scopolamine-induced memory impairment was evaluated in mice. We found that γ-mangostin exhibited prominent protection against H2O2- or xanthine/xanthine oxidase-induced oxidative neuronal death and inhibited reactive oxygen species (ROS) generation triggered by these oxidative insults. In contrast, α-mangostin had no effects on the oxidative neuronal damage or associated ROS production. We also found that γ-mangostin, not α-mangostin, significantly inhibited H2O2-induced DNA fragmentation and activation of caspases 3 and 9, demonstrating its antiapoptotic action. In addition, only γ-mangostin was found to effectively inhibit lipid peroxidation and DPPH radical formation, while both mangostins inhibited β-secretase activity. Furthermore, we observed that the oral administration of γ-mangostin at dosages of 10 and 30 mg/kg markedly improved scopolamine-induced memory impairment in mice. Collectively, these results provide both in vitro and in vivo evidences for the neuroprotective and memory enhancing effects of γ-mangostin. Multiple mechanisms underlying this neuroprotective action were suggested in this study. Based on our findings, γ-mangostin could serve as a potentially preferable candidate over α-mangostin in combatting oxidative stress-associated neurodegenerative diseases including Alzheimer’s disease.

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