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1.
Artigo em Inglês | MEDLINE | ID: mdl-38334084

RESUMO

Mostly, cardiovascular diseases are blamed for casualties in rheumatoid arthritis (RA) patients. Customarily, dyslipidemia is probably the most prevalent underlying cause of untimely demise in people suffering from RA as it hastens the expansion of atherosclerosis. The engagement of inflammatory cytokines like tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), etc., is crucial in the progression and proliferation of both RA and abnormal lipid parameters. Thus, lipid abnormalities should be monitored frequently in patients with both primary and advanced RA stages. An advanced lipid profile examination, i.e., direct role of apolipoproteins associated with various lipid molecules is a more dependable approach for better understanding of the disease and selecting suitable therapeutic targets. Therefore, studying their apolipoproteins is more relevant than assessing RA patients' altered lipid profile levels. Among the various apolipoprotein classes, Apo A1 and Apo B are primarily being focused. In addition, it also addresses how calculating Apo B:Apo A1 ratio can aid in analyzing the disease's risk. The marketed therapies available to control lipid abnormalities are associated with many other risk factors. Hence, directly targeting Apo A1 and Apo B would provide a better and safer option.

2.
Pathol Res Pract ; 254: 155131, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38309018

RESUMO

Diabetes has been a significant healthcare problem worldwide for a considerable period. The primary objective of diabetic treatment plans is to control the symptoms associated with the pathology. To effectively combat diabetes, it is crucial to comprehend the disease's etiology, essential factors, and the relevant processes involving ß-cells. The development of the pancreas, maturation, and maintenance of ß-cells, and their role in regular insulin function are all regulated by PDX1. Therefore, understanding the regulation of PDX1 and its interactions with signaling pathways involved in ß-cell differentiation and proliferation are crucial elements of alternative diabetes treatment strategies. The present review aims to explore the protective role of PDX1 in ß-cell proliferation through signaling pathways. The main keywords chosen for this review include "PDX1 for ß-cell mass," "ß-cell proliferation," "ß-cell restoration via PDX1," and "mechanism of PDX1 in ß-cells." A comprehensive literature search was conducted using various internet search engines, such as PubMed, Science Direct, and other publication databases. We summarize several approaches to generating ß-cells from alternative cell sources, employing PDX1 under various modified growth conditions and different transcriptional factors. Our analysis highlights the unique potential of PDX1 as a promising target in molecular and cell-based therapies for diabetes.


Assuntos
Diabetes Mellitus , Proteínas de Homeodomínio , Células Secretoras de Insulina , Transativadores , Humanos , Diabetes Mellitus/terapia , Diabetes Mellitus/metabolismo , Proteínas de Homeodomínio/metabolismo , Células Secretoras de Insulina/metabolismo , Transativadores/metabolismo , Fatores de Transcrição/metabolismo
3.
Stem Cells Int ; 2024: 9077926, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38213742

RESUMO

Angiogenesis plays a significant role in the human body, from wound healing to tumor progression. "Angiogenic switch" indicates a time-restricted event where the imbalance between pro- and antiangiogenic factors results in the transition from prevascular hyperplasia to outgrowing vascularized tumor, which eventually leads to the malignant cancer progression. In the last decade, molecular players, i.e., angiogenic biomarkers and underlying molecular pathways involved in tumorigenesis, have been intensely investigated. Disrupting the initiation and halting the progression of angiogenesis by targeting these biomarkers and molecular pathways has been considered as a potential treatment approach for tumor angiogenesis. This review discusses the currently known biomarkers and available antiangiogenic therapies in cancer, i.e., monoclonal antibodies, aptamers, small molecular inhibitors, miRNAs, siRNAs, angiostatin, endostatin, and melatonin analogues, either approved by the U.S. Food and Drug Administration or currently under clinical and preclinical investigations.

4.
Int J Biol Macromol ; 254(Pt 2): 127735, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37923047

RESUMO

Gelatin-based hydrogels have been widely used for wound healing applications. However, increase in ligand density and reduction in pore size with increasing gelatin concentration may delay wound healing by limiting cell infiltration. In this study, we address this shortcoming by combining gelatin with gellan-which is super hydrophilic and non-adhesive to cells. We show that UV crosslinked hybrid gels composed of methacrylated gelatin (GelMA) and methacrylated gellan gum (mGG), possess considerably larger pores and improved mechanical properties compared to GelMA gels. Reduced spreading and reduced formation of focal adhesions on hybrid gels combined with lower contractility and faster detachment upon trypsin-induced de-adhesion suggests that hybrid gels are less adhesive than GelMA gels. Gradual release of fibroblast growth factor (FGF) and silver nanoparticles (AgNPs) incorporated in hybrid gels not only boosts cell migration, but also confers anti-bacterial activity against gram-positive and gram-negative bacteria at concentrations nontoxic to cells. Full thickness wound healing in Wistar rats revealed increased granulation tissue formation in hybrid gels, fastest epithelialization and highest collagen deposition in rats treated with FGF entrapped hybrid gels. Together, our results demonstrate how adhesive tuning and incorporation of bioactive factors can be synergistically combined for achieving complete wound healing.


Assuntos
Gelatina , Nanopartículas Metálicas , Ratos , Animais , Gelatina/farmacologia , Antibacterianos/farmacologia , Adesivos/farmacologia , Ratos Wistar , Bactérias Gram-Negativas , Bactérias Gram-Positivas , Prata/farmacologia , Cicatrização , Hidrogéis/farmacologia
5.
Am J Transl Res ; 15(11): 6321-6341, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38074830

RESUMO

Reactive oxygen species (ROS) play a crucial role in cell survival regulation, and its low levels may act as indicators to encourage cellular proliferation. In contrast, elevated levels of ROS may lead to apoptosis. Stability between generating and eliminating ROS allows the retention of effective functioning of redox-sensitive signaling proteins under physiologic conditions. Cells typically maintain redox homeostasis to guarantee appropriate responses to internal and external stimuli. However, oxidative stress occurs when the oxidation product level exceeds the number of standard antioxidant systems. ROS can cause harm to all types of hepatic cells, including endothelial cells, hepatocytes, Kupffer cells, and stellate cells. High levels of ROS may lead to tissue edema, ischemia, fibrosis, cell death, or malignant transformation and may eventually lead to complete tissue damage. Antioxidants in our body exist in a homeostatic balance with other enzymes involved in the repair of cellular functions in addition to the non-enzymatic molecules such as urate, bilirubin, several vitamins, and reduced glutathione to maintain the levels of ROS in the interest of cellular homeostasis. This balance may, however, get disturbed in case of acute or chronic liver injury due to the accumulation of ROS. In the current manuscript, we aim to review the relevance of oxidative stress and its indicator of liver injury in chronic liver diseases such as alcoholic and non-alcoholic fatty liver diseases and hepatitis. Since reactive oxidation species may also lead to lipid peroxidation and promote ferroptosis, we have also evaluated their impact on epigenetic modifications, such as oxidative damage to histone proteins and DNA methylation, and the differential expression of genes related to cellular injury. We also want to highlight the potential of traditional herbal medicines as redox regulators for managing chronic liver diseases.

6.
Saudi Pharm J ; 31(7): 1274-1293, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37304359

RESUMO

Postpartum depression (PPD) is a challenging psychological disorder faced by 10-30% of mothers across the globe. In India, it occurs among 22% of mothers. Its aetiology and pathophysiology aren't fully understood as of today but multiple theories on the interplay of hormones, neurotransmitters, genetics, epigenetics, nutrients, socio-environmental factors, etc. exist. Nutrients are not only essential for the synthesis of neurotransmitters, but they may also indirectly influence genomic pathways that methylate DNA, and there is evidence for molecular associations between nutritional quality and psychological well-being. Increased behavioural disorders have been attributed to macro- and micronutrient deficiencies, and dietary supplementation has been effective in treating several neuropsychiatric illnesses. Nutritional deficiencies occur frequently in women, especially during pregnancy and breastfeeding. The aim of this study was to perform a comprehensive literature review of evidence-based research in order to identify, gather and summarize existing knowledge on PPD's aetiology, pathophysiology, and the role of nutrients in its prevention as well as management. The possible mechanisms of action of nutrients are also presented here. Study findings show that the risk of depression increases when omega-3 fatty acid levels are low. Both fish oil and folic acid supplements have been used to effectively treat depression. Antidepressant efficacy is lowered by folate insufficiency. Folate, vitamin B12, iron, etc. deficiencies are more prevalent in depressed people than in non-depressed people. Serum cholesterol levels and plasma tryptophan levels are found to be inversely correlated with PPD. Serum vitamin D levels were associated inversely with perinatal depression. These findings highlight the importance of adequate nutrition in the antepartum period. Given that nutritional therapies can be affordable, safe, simple to use, and are typically well-accepted by patients, more focus should be placed on dietary variables in PPD.

7.
Int J Biol Macromol ; 242(Pt 1): 124581, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37105251

RESUMO

Sirtuins or Sir (Silent information regulator) are NAD+-dependent enzymes playing an important part in the pathogenesis and treatment of various disorders. They have ubiquitously expressed protein deacetylases. They are implicated in several cellular activities like DNA repair, cellular metabolism, mitochondrial function, and inflammation. Deletion of sirtuin protein, SIRT1 in the organs like brain, heart, liver and pancreas can cause inflammation and increases the level of free radical ions causing oxidative stress. Inflammation and oxidative stress are closely associated with pathophysiological events in many chronic diseases, like diabetes, cancer, cardiovascular, osteoporosis, and neurodegenerative diseases. Modulation of SIRT1 gene expression might help in preventing the progression of chronic diseases related to the brain, heart, liver, and pancreas. SIRT2 proteins play an essential role in tumorigenesis, including tumor-suppressing and tumor-promoting functions. Sirtuin activators are molecules that upregulate the activity of Sirtuins in the body. Their multifaceted uses have surprised the global scientific community. They are found to control obesity, lower cardiac risks, battle cancer, etc. This article provides an update on the pharmacological effect of SIRT1 and SIRT 2 proteins, their activators and inhibitors, and their molecular mechanism. It provides novel insights for future research in targeted therapy and drug development.


Assuntos
Neoplasias , Sirtuína 1 , Humanos , Sirtuína 1/genética , Sirtuína 1/metabolismo , Estresse Oxidativo , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Mitocôndrias/metabolismo , Inflamação/metabolismo
8.
Pathophysiology ; 29(2): 200-222, 2022 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-35736645

RESUMO

Cancer cells undergo transient EMT and MET phenomena or vice versa, along with the parallel interplay of various markers, often correlated as the determining factor in decoding metabolic profiling of breast cancers. Moreover, various cancer signaling pathways and metabolic changes occurring in breast cancer cells modulate the expression of such markers to varying extents. The existing research completed so far considers the expression of such markers as determinants regulating the invasiveness and survival of breast cancer cells. Therefore, this manuscript is crosstalk among the expression levels of such markers and their correlation in regulating the aggressiveness and invasiveness of breast cancer. We also attempted to cover the possible EMT-based metabolic targets to retard migration and invasion of breast cancer.

9.
Can J Physiol Pharmacol ; 100(3): 272-281, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35119950

RESUMO

The activation of Nod-like receptor proteins (NLRP3) containing the pyrin domain inflammasome is a hallmark of the pathogenesis of metabolic disorders. Inhibition of the NLRP3 inflammasome by phytoconstituents has been attempted as a strategy to mitigate these disorders. Therefore, the present study aimed to evaluate the efficacy of an NLRP3 inflammasome inhibitor, parthenolide (PN; 5 mg/kg i.p.) against inflammation and insulin resistance in high-fat diet (HFD) - obese mice. Treatment with PN and pioglitazone (PIO; 30 mg/kg p.o.) attenuated lipopolysaccharide (LPS; 1 ng/ml) - induced elevation of tumor necrosis factor-α and interleukin-1ß in mouse peritoneal macrophages in a dose-dependent manner. Sixty days of PN and PIO treatment marginally reduced obesity-induced insulin resistance in HFD-obese mice. PN treatment also decreased blood glucose from 14th to 60th day, supporting the hypothesis of simultaneous attenuation of inflammation and insulin resistance in obese mice. Thus, PN treatment was also evident with significant improvement in glucose tolerance and peripheral insulin resistance validated through the respective tolerance tests. Therefore, the present study suggests that PN, an NLRP3 inflammasome inhibitor, could be a possible therapeutic agent for attenuating obesity-induced insulin resistance.


Assuntos
Dieta Hiperlipídica/efeitos adversos , Resistência à Insulina , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Obesidade/tratamento farmacológico , Obesidade/fisiopatologia , Sesquiterpenos/farmacologia , Animais , Glicemia/metabolismo , Relação Dose-Resposta a Droga , Interleucina-1beta/metabolismo , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Pioglitazona/farmacologia , Pioglitazona/uso terapêutico , Sesquiterpenos/uso terapêutico , Fator de Necrose Tumoral alfa/metabolismo
10.
Can J Physiol Pharmacol ; 100(3): 210-219, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-34910610

RESUMO

Our current investigation comprises the synthesis and pharmacological impact of bromelain copper nanoparticles (BrCuNP) against diabetes mellitus (DM) and associated ischemia/reperfusion (I/R) - induced myocardial infarction. Bromelain is a proteolytic enzyme obtained from Ananas comosus L. Merr., which has blood platelet aggregation inhibiting and arterial thrombolytic potential. Moreover, copper is well-known to facilitate glucose metabolism and strengthen cardiac muscle and antioxidant activity; although, chronic or long-term exposure to high doses of copper may lead to copperiedus. To restrict these potential hazards, we synthesized herbal nano-formulation which convincingly indicated the improved primordial therapeutic potential of copper by reformulating the treatment carrier with bromelain, resulting in facile synthesis of BrCuNP. DM was induced by administration of double cycle repetitive dose of low dose streptozotocin (20 mg/kg, i.p.) in high-fat diet- fed animals. DM and associated myocardial I/R injury were estimated by increased serum levels of total cholesterol, low-density lipoprotein, very low-density lipoprotein, lactate dehydrogenase, creatine kinase myocardial band, cardiac troponin, thiobarbituric acid reactive substances, tumor necrosis factor α, interleukin 6, and reduced serum level of high-density lipoprotein and nitrite/nitrate concentration. However, treatment with BrCuNP ameliorates various serum biomarkers by approving cardioprotective potential against DM- and I/R-associated injury. Furthermore, upturn of histopathological changes were observed in cardiac tissue of BrCuNP-treated rats in comparison to disease models.


Assuntos
Bromelaínas/síntese química , Bromelaínas/uso terapêutico , Cobre/química , Cobre/uso terapêutico , Complicações do Diabetes/complicações , Nanopartículas Metálicas/química , Nanopartículas Metálicas/uso terapêutico , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/etiologia , Traumatismo por Reperfusão Miocárdica/complicações , Animais , Bromelaínas/farmacologia , Cobre/farmacologia , Modelos Animais de Doenças , Feminino , Ratos Wistar
11.
Heart Fail Rev ; 26(6): 1495-1504, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-32314086

RESUMO

The finding of "glycogen synthase kinase-3" (GSK-3) was initially identified as a protein kinase that phosphorylate and inhibited glycogen synthase. However, it was soon discovered that GSK-3 also has significant impact in regulation of truly astonishing number of critical intracellular signaling pathways ranging from regulation of cell growth, neurology, heart failure, diabetes, aging, inflammation, and cancer. Recent studies have validated the feasibility of targeting GSK-3 for its vital therapeutic potential to maintain normal myocardial homeostasis, conversely, its loss is incompatible with life as it can abrupt cell cycle and endorse fatal cardiomyopathy. The current study focuses on its expanding therapeutic action in myocardial tissue, concentrating primarily on its role in diabetes-associated cardiac complication, apoptosis and metabolism, heart failure, cardiac hypertrophy, and myocardial infarction. The current report also includes the finding of our previous investigation that has shown the impact of GSK-3ß inhibitor against diabetes-associated myocardial injury and experimentally induced myocardial infarction. We have also discussed some recent identified GSK-3ß inhibitors for their cardio-protective potential. The crosstalk of various underlying mechanisms that highlight the significant role of GSK-3ß in myocardial pathophysiology have been discussed in the present report. For these literatures, we will rely profoundly on our previous studies and those of others to reconcile some of the deceptive contradictions in the literature.


Assuntos
Quinase 3 da Glicogênio Sintase , Infarto do Miocárdio , Cardiomegalia , Glicogênio Sintase Quinase 3 beta , Humanos , Miocárdio
12.
3 Biotech ; 10(8): 338, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32670738

RESUMO

The current study focuses on the evaluation of the chemoprophylactic activity of nitazoxanide against the mammary gland carcinoma in experimental rats. The experimental protocol involves total 50 female Wistar albino rats of body weight 120-150 g, which were randomly categorized into five groups; Normal control (1% w/v carboxymethyl cellulose, p.o.); Toxic control (N-methyl-N-nitrosourea, MNU, 47 mg/kg i.v.); Standard (MNU, 47 mg/kg i.v. + tamoxifen, 1 mg/kg p.o.); Treatment 1 (MNU, 47 mg/kg i.v. + NTZ low-dose, 25 mg/kg p.o.); and Treatment 2 (MNU, 47 mg/kg, i.v. + NTZ high-dose, 50 mg/kg p.o.). The mammary gland carcinoma was induced by a single tail vein intravenous injection of MNU at a 47 mg/kg dose. Seven days after MNU administration, daily dosing of nitazoxanide and tamoxifen was initiated till 110th day in respective groups. The MNU toxicity was apparent with the altered electrocardiogram and heart rate variability, increased number of alveolar bud count, differentiation score, and upregulated antioxidant parameters. Nitazoxanide treatment restored the histological architecture in rats along with the reduction of alveolar buds and downregulation of oxidative stress markers as well as inflammatory markers. Therefore, nitazoxanide can be utilized as a potential chemoprophylactic agent against mammary gland carcinoma induced by MNU.

13.
Drug Res (Stuttg) ; 70(2-03): 65-70, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31931549

RESUMO

Tuberculosis (TB) is one of the oldest fatal diseases of history. Multidrugresistant tuberculosis (MDRTB) is a major public health issue in the world. In India, the incidence is getting up despite the Indian revised National Tuberculosis Control Programme. India has six recognize medicine systems in this category, namely Ayurveda, Siddha, Unani and Yoga, Naturopathy and Homoeopathy. This review study was undertaken to evaluate the efficacy of different drug treatments based on Indian Systems of Traditional Medicines to the standard MDR-TB regimen. This review mainly focuses on the combinational approaches towards treatment protocols, prevention strategies, and management of tuberculosis in different established systems of medicine in India. Along with allopathic drugs, these AYUSH based drugs work in synergistic manner. Recent research suggests that Homeopathic treatment along with the antibiotics synergise the effect of antibiotics while reaching to its site of action. Additionally in Siddha system, formulation of medicinal herbs showing significant activity against TB bacteria. Furthermore, adopting the management or principles of Unani system would be beneficial in health and disease. Similarly, Unani and Naturopathy through natural healing are equally effective. On the other hand, medicinal plants from the Ayurveda that have been successfully employed to treat TB because of less toxicity and side effect in comparison with existing antibiotics. The findings in this review have provided scientific support for anti-TB activity of different medicinal system of India via numerous underlying mechanisms.


Assuntos
Antituberculosos/administração & dosagem , Medicina Tradicional/métodos , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Antituberculosos/efeitos adversos , Antituberculosos/farmacologia , Sinergismo Farmacológico , Quimioterapia Combinada , Humanos , Índia/epidemiologia , Mycobacterium tuberculosis/efeitos dos fármacos , Mycobacterium tuberculosis/isolamento & purificação , Plantas Medicinais/química , Tuberculose Resistente a Múltiplos Medicamentos/epidemiologia , Tuberculose Resistente a Múltiplos Medicamentos/microbiologia
15.
Drug Dev Res ; 80(6): 758-777, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31199023

RESUMO

System xc- (Sxc- ), a cystine-glutamate antiporter, is established as an interesting target for the treatment of several pathologies including epileptic seizures, glioma, neurodegenerative diseases, and multiple sclerosis. Erastin, sorafenib, and sulfasalazine (SSZ) are a few of the established inhibitors of Sxc- . However, its pharmacological inhibition with novel and potent agents is still very much required due to potential issues, for example, potency, bioavailability, and blood-brain barrier (BBB) permeability, with the current lead molecules such as SSZ. Therefore, in this study, we report the synthesis and structure-activity relationships (SAR) of SSZ derivatives along with molecular docking and dynamics simulations using the developed homology model of xCT chain of Sxc- antiporter. The generated homology model attempted to address the limitations of previously reported comparative protein models, thereby increasing the confidence in the computational modeling studies. The main objective of the present study was to derive a suitable lead structure from SSZ eliminating its potential issues for the treatment of glioblastoma multiforme (GBM), a deadly and malignant grade IV astrocytoma. The designed compounds with favorable Sxc- inhibitory activity following in vitro Sxc- inhibition studies, showed moderately potent cytotoxicity in patient-derived human glioblastoma cells, thereby generating potential interest in these compounds. The xCT-ligand model can be further optimized in search of potent lead molecules for novel drug discovery and development studies.


Assuntos
Sistema y+ de Transporte de Aminoácidos/antagonistas & inibidores , Antiporters/antagonistas & inibidores , Sulfassalazina/análogos & derivados , Sistema y+ de Transporte de Aminoácidos/metabolismo , Animais , Antiporters/metabolismo , Sítios de Ligação , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Humanos , Ligantes , Simulação de Acoplamento Molecular , Ratos , Relação Estrutura-Atividade , Sulfassalazina/química , Sulfassalazina/farmacocinética , Sulfassalazina/farmacologia
16.
Oxid Med Cell Longev ; 2017: 2359389, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28798859

RESUMO

The present study evaluates the protective effects of an antioxidant-rich extract of Spinacea oleracea (NAOE) in abnormalities associated with the metabolic syndrome (MetS) in rats. HPTLC of NAOE revealed the presence of 13 total antioxidants, 14 flavonoids, and 10 phenolic acids. Rats administered with fructose (20% w/v) in drinking water for 45 days to induce abnormalities of MetS received NAOE (200 and 400 mg/kg, po), the standard drug gemfibrozil (60 mg/kg, po), aerobic exercise (AE), and a combination of NAOE 400 mg/kg and AE (NAOEAE) daily for 45 days. All treatments significantly altered the lipid profile and attenuated the fructose-elevated levels of uric acid, C-reactive protein, homocysteine, and marker enzymes (AST, LDH, and CK-MB) in serum and malondialdehyde in the heart and restored the fructose-depleted levels of glutathione and antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase). A significant decrease in blood glucose and insulin levels decreased insulin resistance, and improved glucose tolerance was observed in the treatment animals when compared with the fructose-fed animals. The best mitigation of MetS was shown by the NAOEAE treatment indicating that regular exercise along with adequate consumption of antioxidant-rich foods such as spinach in diet can help control MetS.


Assuntos
Síndrome Metabólica/tratamento farmacológico , Condicionamento Físico Animal/fisiologia , Extratos Vegetais/uso terapêutico , Spinacia oleracea/química , Animais , Antioxidantes/metabolismo , Proteína C-Reativa/metabolismo , Feminino , Frutose/farmacologia , Genfibrozila/uso terapêutico , Glutationa Peroxidase/metabolismo , Homocisteína/sangue , Insulina/sangue , Peroxidação de Lipídeos/efeitos dos fármacos , Malondialdeído/metabolismo , Síndrome Metabólica/sangue , Estresse Oxidativo/efeitos dos fármacos , Ratos , Superóxido Dismutase/metabolismo , Ácido Úrico/sangue
17.
J Surg Res ; 213: 90-99, 2017 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-28601338

RESUMO

BACKGROUND: Presence of circulating endothelial cells (CECs) in systemic circulation may be an indicator of endothelial damage and/or denudation, and the body's response to repair and revascularization. Thus, we hypothesized that aggregated platelets (AgPlts) can disrupt/denude the endothelium and contribute to the presence of CEC and EC-derived particles (ECDP). METHODS: Endothelial cells were grown in glass tubes and tagged with/without 0.5 µm fluorescent beads. These glass tubes were connected to a mini-pump variable-flow system to study the effect of circulating AgPlts on the endothelium. ECs in glass tube were exposed to medium alone, nonaggregated platelets (NAgPlts), AgPlts, and 90 micron polystyrene beads at a flow rate of 20 mL/min for various intervals. Collected effluents were cultured for 72 h to analyze the growth potential of dislodged but intact ECs. Endothelial damage was assessed by real time polymerase chain reaction (RT-PCR) for inflammatory genes and Western blot analysis for von Willebrand factor. RESULTS AND CONCLUSION: No ECs and ECDP were observed in effluents collected after injecting medium alone and NAgPlts, whereas AgPlts and Polybeads drastically dislodged ECs, releasing ECs and ECDP in effluents as the time increased. Effluents collected when endothelial cell damage was seen showed increased presence of von Willebrand factor as compared to control effluents. Furthermore, we analyzed the presence of ECs and ECDPs in heart failure subjects, as well as animal plasma samples. Our study demonstrates that circulating AgPlts denude the endothelium and release ECs and ECDP. Direct mechanical disruption and shear stress caused by circulating AgPlts could be the underlying mechanism of the observed endothelium damage.


Assuntos
Plaquetas/fisiologia , Células Endoteliais/fisiologia , Células Endoteliais da Veia Umbilical Humana/fisiologia , Agregação Plaquetária/fisiologia , Animais , Biomarcadores/metabolismo , Western Blotting , Células Cultivadas , Ensaio de Imunoadsorção Enzimática , Humanos , Reação em Cadeia da Polimerase em Tempo Real , Ovinos
18.
Am J Transl Res ; 9(3): 830-844, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28386316

RESUMO

Emerging evidence suggests that, dysregulation of fatty acid synthase (FASN) and insulin-like growth factor-1 (IGF-1) could play a vital role in pathology of various diseases. Our aim was to determine the changes in FASN and IGF-1 levels concomitant to long term feeding of HFD in either sex. Male and female mice were fed either HFD or LFD for a period of 16 weeks. During this period, physiological, biochemical, and histological parameters were evaluated. Mice fed with HFD showed a significant gain in body weight, body mass index, energy intake, and abdominal circumference. These changes were accompanied by compromised glucose and insulin tolerance, hyperinsulinemia, dyslipidemia, elevated plasma IL-6, and TNF-α concentration. Histologically, hepatocytes showed an elevated fat accumulation, appended by an increase in plasma activities of liver enzymes. Pancreas showed upsurge in number of ß-cells with subsequent increase in size of islet implying its compromised state. While the kidney showed mild tubulointerstitial fibrosis indicating initiation of kidney impairment. These metabolic perturbations were related to the energy intake which was higher in males as compared to females. This led to a proportional rise in plasma as well as liver FASN and IGF-1 in HFD fed mice. Within both sexes, mice fed with HFD developed features of non-alcoholic steatohepatitis (NASH), hyperinsulinemia, dyslipidemia, impaired glucose and insulin tolerance but the magnitude of these abnormalities was found to be less in female mice. This variation in magnitude could be attributed to the difference in energy intake and ultimately its effect on FASN and IGF-1 levels.

19.
Oxid Med Cell Longev ; 2017: 3876040, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28168009

RESUMO

Phyllanthus emblica L. (amla) has been used in Ayurveda as a potent rasayan for treatment of hepatic disorders. Most of the pharmacological studies, however, are largely focused on PE fruit, while the rest of the parts of PE, particularly, bark, remain underinvestigated. Therefore, we aimed to investigate the protective effect of the hydroalcoholic extract of Phyllanthus emblica bark (PEE) in ethanol-induced hepatotoxicity model in rats. Total phenolic, flavonoid, and tannin content and in vitro antioxidant activities were determined by using H2O2 scavenging and ABTS decolorization assays. Our results showed that PEE was rich in total phenols (99.523 ± 1.91 mg GAE/g), total flavonoids (389.33 ± 1.25 mg quercetin hydrate/g), and total tannins (310 ± 0.21 mg catechin/g), which clearly support its strong antioxidant potential. HPTLC-based quantitative analysis revealed the presence of the potent antioxidants gallic acid (25.05 mg/g) and ellagic acid (13.31 mg/g). Moreover, one-month PEE treatment (500 and 1000 mg/kg, p.o.) followed by 30-day 70% ethanol (10 mL/kg) administration showed hepatoprotection as evidenced by significant restoration of ALT (p < 0.01), AST (p < 0.001), ALP (p < 0.05), and TP (p < 0.001) and further confirmed by liver histopathology. PEE-mediated hepatoprotection could be due to its free radical scavenging and antioxidant activity that may be ascribed to its antioxidant components, namely, ellagic acid and gallic acid. Thus, the results of the present study support the therapeutic claims made in Ayurveda about Phyllanthus emblica.


Assuntos
Etanol/efeitos adversos , Frutas/química , Fígado/patologia , Phyllanthus emblica/química , Extratos Vegetais/química , Animais , Antioxidantes/metabolismo , Modelos Animais de Doenças , Masculino , Ratos , Ratos Wistar , Silimarina
20.
Phytother Res ; 30(7): 1146-55, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27091200

RESUMO

The present study investigates the cardioprotective activity of the Macrotyloma uniflorum seed extract (MUSE) and its phenolic acids (p-coumaric acid and ferulic acid) in isoproterenol (ISO)-induced myocardial infarction in rats. The previously mentioned phenolic acids were isolated and quantified from MUSE by HPLC. Pretreatment of gemfibrozil (reference standard), MUSE (250 and 500 mg/kg) and the phenolic acids for 30 days to rats treated with ISO (85 mg/kg) on the last 2 days resulted in a significant attenuation of the ISO-elevated levels of serum marker enzymes (aspartate aminotransferase, lactate dehydrogenase and creatine phosphokinase MB), total cholesterol, triglycerides, uric acid, C-reactive protein and malondialdehyde and a restoration of the levels of the ISO-depleted marker enzymes, reduced glutathione and the antioxidant enzymes-superoxide dismutase, catalase, glutathione peroxidase and glutathione reductase in heart. Restoration of the ISO-altered electrocardiogram pattern and haemodynamic parameters (left ventricular end diastolic pressure, heart rate, systolic, diastolic and mean arterial pressure) was also brought about by treatment with MUSE and the phenolic acids. It may be concluded that MUSE treatment to ISO-challenged rats exhibits a significant cardioprotective effect probably because of the potent antioxidant activity of its phenolic acids that salvage the myocardium from the deleterious effects of ISO. Copyright © 2016 John Wiley & Sons, Ltd.


Assuntos
Fabaceae/química , Hidroxibenzoatos/administração & dosagem , Isoproterenol/farmacologia , Infarto do Miocárdio/prevenção & controle , Animais , Antioxidantes/farmacologia , Coração/efeitos dos fármacos , Masculino , Extratos Vegetais/farmacologia , Substâncias Protetoras/farmacologia , Ratos , Ratos Wistar
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