scholarly journals Effects and Mechanisms of Tea Regulating Blood Pressure: Evidences and Promises

Nutrients ◽  
2019 ◽  
Vol 11 (5) ◽  
pp. 1115 ◽  
Author(s):  
Daxiang Li ◽  
Ruru Wang ◽  
Jinbao Huang ◽  
Qingshuang Cai ◽  
Chung S. Yang ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Animal Studies ◽  
Large Scale ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Vascular Inflammation ◽  
Optimal Dose ◽  
Smooth Muscle Contraction ◽  
Beneficial Effects ◽  
Underlying Mechanisms

Cardiovascular diseases have overtaken cancers as the number one cause of death. Hypertension is the most dangerous factor linked to deaths caused by cardiovascular diseases. Many researchers have reported that tea has anti-hypertensive effects in animals and humans. The aim of this review is to update the information on the anti-hypertensive effects of tea in human interventions and animal studies, and to summarize the underlying mechanisms, based on ex-vivo tissue and cell culture data. During recent years, an increasing number of human population studies have confirmed the beneficial effects of tea on hypertension. However, the optimal dose has not yet been established owing to differences in the extent of hypertension, and complicated social and genetic backgrounds of populations. Therefore, further large-scale investigations with longer terms of observation and tighter controls are needed to define optimal doses in subjects with varying degrees of hypertensive risk factors, and to determine differences in beneficial effects amongst diverse populations. Moreover, data from laboratory studies have shown that tea and its secondary metabolites have important roles in relaxing smooth muscle contraction, enhancing endothelial nitric oxide synthase activity, reducing vascular inflammation, inhibiting rennin activity, and anti-vascular oxidative stress. However, the exact molecular mechanisms of these activities remain to be elucidated.

SGLT2 inhibition for cardiovascular diseases, chronic kidney disease and NAFLD

Endocrinology ◽  
2021 ◽  
Author(s):  
Moein Ala
Keyword(s):  
Chronic Kidney Disease ◽  
Clinical Trials ◽  
Cardiovascular Diseases ◽  
Kidney Disease ◽  
Signaling Pathways ◽  
Observational Studies ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Renal Diseases ◽  
Beneficial Effects

Abstract Sodium glucose cotransporter 2 (SGLT-2) inhibitors are the latest class of anti-diabetic medications. They prevent glucose reabsorption in the proximal convoluted tubule to decrease blood sugar. Several animal studies revealed that SGLT-2 is profoundly involved in the inflammatory response, fibrogenesis and regulation of numerous intracellular signaling pathways. Likewise, SGLT-2 inhibitors markedly attenuated inflammation and fibrogenesis and improved the function of damaged organ in animal studies, observational studies and clinical trials. SGLT-2 inhibitors can decrease blood pressure and ameliorate hypertriglyceridemia and obesity. Likewise, they improve the outcome of cardiovascular diseases such as heart failure, arrhythmias and ischemic heart disease. SGLT-2 inhibitors are associated with lower cardiovascular and all-cause mortality, as well. Meanwhile, they protect against non-alcoholic fatty liver disease (NAFLD), chronic kidney disease (CKD), acute kidney injury (AKI), and improve micro- and macroalbuminuria. SGLT-2 inhibitors can reprogram numerous signaling pathways to improve NAFLD, cardiovascular diseases and renal diseases. For instance, they enhance lipolysis, ketogenesis, mitochondrial biogenesis and autophagy while they attenuate renin-angiotensin-aldosterone system (RAAS), lipogenesis, endoplasmic reticulum (ER) stress, oxidative stress, apoptosis and fibrogenesis. This review explains the beneficial effects of SGLT-2 inhibitors on NAFLD, cardiovascular and renal diseases and dissects the underlying molecular mechanisms in detail. This narrative review explains the beneficial effects of SGLT-2 inhibitors on NAFLD, cardiovascular and renal diseases using the results of latest observational studies, clinical trials and meta-analyses. Thereafter, it dissects the underlying molecular mechanisms involved in the clinical effects of SGLT-2 inhibitors on these diseases.

scholarly journals Type 1 Diabetic Neuropathy and C-peptide

2004 ◽  
Vol 5 (1) ◽  
pp. 65-77 ◽  
Author(s):  
Anders A. F. Sima ◽  
Weixian Zhang ◽  
George Grunberger
Keyword(s):  
Clinical Trials ◽  
Animal Studies ◽  
Large Scale ◽  
Structural Changes ◽  
Diabetic Complication ◽  
Diabetic Patients ◽  
C Peptide ◽  
Beneficial Effects ◽  
Regulatory Effects

The most common microvascular diabetic complication, diabetic peripheral polyneuropathy (DPN), affects type 1 diabetic patients more often and more severely. In recent decades, it has become increasingly clear that perpetuating pathogenetic mechanisms, molecular, functional, and structural changes and ultimately the clinical expression of DPN differ between the two major types of diabetes. Impaired insulin/C-peptide action has emerged as a crucial factor to account for the disproportionate burden affecting type 1 patients. C-peptide was long believed to be biologically inactive. However, it has now been shown to have a number of insulin-like glucoseindependent effects. Preclinical studies have demonstrated dose-dependent effects onNa+,K+-ATPase activity, endothelial nitric oxide synthase (eNOS), and endoneurial blood flow. Furthermore, it has regulatory effects on neurotrophic factors and molecules pivotal to the integrity of the nodal and paranodal apparatus and modulatory effects on apoptotic phenomena affecting the diabetic nervous system. In animal studies, C-peptide improves nerve conduction abnormalities, prevents nodal degenerative changes, characteristic of type 1 DPN, promotes nerve fiber regeneration, and prevents apoptosis of central and peripheral nerve cell constituents. Limited clinical trials have confirmed the beneficial effects of C-peptide on autonomic and somatic nerve function in patients with type 1 DPN. Therefore, evidence accumulates that replacement of C-peptide in type 1 diabetes prevents and even improves DPN. Large-scale food and drug administration (FDA)-approved clinical trials are necessary to make this natural substance available to the globally increasing type 1 diabetic population.

scholarly journals Normothermic Ex-vivo Kidney Perfusion in a Porcine Auto-Transplantation Model Preserves the Expression of Key Mitochondrial Proteins: An Unbiased Proteomics Analysis

2020 ◽  
Author(s):  
Caitriona M. McEvoy ◽  
Sergi Clotet-Freixas ◽  
Tomas Tokar ◽  
Chiara Pastrello ◽  
Shelby Reid ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Ischemia Reperfusion Injury ◽  
Ex Vivo ◽  
Ischemia Reperfusion ◽  
Graft Function ◽  
Kidney Injury ◽  
Tca Cycle ◽  
Proteomics Analysis ◽  
Beneficial Effects ◽  
Kidney Perfusion

AbstractNormothermic ex-vivo kidney perfusion (NEVKP) results in significantly improved graft function in porcine auto-transplant models of DCD injury compared to static cold storage (SCS); however, the molecular mechanisms underlying these beneficial effects remain unclear. We performed an unbiased proteomics analysis of 28 kidney biopsies obtained at 3 time points from pig kidneys subjected to 30-minutes of warm ischemia, followed by 8 hours of NEVKP or SCS, and auto-transplantation. 70/6593 proteins quantified were differentially expressed between NEVKP and SCS groups (FDR<0.05). Proteins increased in NEVKP mediated key metabolic processes including fatty acid ß-oxidation, the TCA-cycle and oxidative phosphorylation. Comparison of our findings with external datasets of ischemia-reperfusion, and other models of kidney injury confirmed that 47 of our proteins represent a common signature of kidney injury reversed or attenuated by NEVKP. We validated key metabolic proteins (ETFB, CPT2) by immunoblotting. Transcription factor databases identified PPARGC1A, PPARA/G/D and RXRA/B as the upstream regulators of our dataset, and we confirmed their increased expression in NEVKP with RT-PCR. The proteome-level changes observed in NEVKP mediate critical metabolic pathways that may explain the improved graft function observed. These effects may be coordinated by PPAR-family transcription factors, and may represent novel therapeutic targets in ischemia-reperfusion injury.

scholarly journals Physiological role of ROCKs in the cardiovascular system

2006 ◽  
Vol 290 (3) ◽  
pp. C661-C668 ◽  
Author(s):  
Kensuke Noma ◽  
Naotsugu Oyama ◽  
James K. Liao
Keyword(s):  
Protein Kinase ◽  
Cardiovascular System ◽  
Vascular Inflammation ◽  
Physiological Role ◽  
Smooth Muscle Contraction ◽  
Kinase Substrate ◽  
Cytoskeleton Organization ◽  
Beneficial Effects ◽  
Actin Cytoskeleton Organization

Rho-associated kinases (ROCKs), the immediate downstream targets of RhoA, are ubiquitously expressed serine-threonine protein kinases that are involved in diverse cellular functions, including smooth muscle contraction, actin cytoskeleton organization, cell adhesion and motility, and gene expression. Recent studies have shown that ROCKs may play a pivotal role in cardiovascular diseases such as vasospastic angina, ischemic stroke, and heart failure. Indeed, inhibition of ROCKs by statins or other selective inhibitors leads to the upregulation and activation of endothelial nitric oxide synthase (eNOS) and reduction of vascular inflammation and atherosclerosis. Thus inhibition of ROCKs may contribute to some of the cholesterol-independent beneficial effects of statin therapy. Currently, two ROCK isoforms have been identified, ROCK1 and ROCK2. Because ROCK inhibitors are nonselective with respect to ROCK1 and ROCK2 and also, in some cases, may be nonspecific with respect to other ROCK-related kinases such as myristolated alanine-rich C kinase substrate (MARCKS), protein kinase A, and protein kinase C, the precise role of ROCKs in cardiovascular disease remains unknown. However, with the recent development of ROCK1- and ROCK2-knockout mice, further dissection of ROCK signaling pathways is now possible. Herein we review what is known about the physiological role of ROCKs in the cardiovascular system and speculate about how inhibition of ROCKs could provide cardiovascular benefits.

scholarly journals Phytochemical Compounds and Protection from Cardiovascular Diseases: A State of the Art

2015 ◽  
Vol 2015 ◽  
pp. 1-17 ◽  
Author(s):  
Beniamino Pagliaro ◽  
Caterina Santolamazza ◽  
Francesca Simonelli ◽  
Speranza Rubattu
Keyword(s):  
Cardiovascular Diseases ◽  
Dietary Habits ◽  
Ex Vivo ◽  
Lifestyle Changes ◽  
In Vivo Models ◽  
Beneficial Effects ◽  
Phytochemical Compounds ◽  
Cardioprotective Effects ◽  
Reference Tool

Cardiovascular diseases represent a worldwide relevant socioeconomical problem. Cardiovascular disease prevention relies also on lifestyle changes, including dietary habits. The cardioprotective effects of several foods and dietary supplements in both animal models and in humans have been explored. It was found that beneficial effects are mainly dependent on antioxidant and anti-inflammatory properties, also involving modulation of mitochondrial function. Resveratrol is one of the most studied phytochemical compounds and it is provided with several benefits in cardiovascular diseases as well as in other pathological conditions (such as cancer). Other relevant compounds areBrassica oleracea, curcumin, and berberine, and they all exert beneficial effects in several diseases. In the attempt to provide a comprehensive reference tool for both researchers and clinicians, we summarized in the present paper the existing literature on both preclinical and clinical cardioprotective effects of each mentioned phytochemical. We structured the discussion of each compound by analyzing, first, its cellular molecular targets of action, subsequently focusing on results from applications in both ex vivo and in vivo models, finally discussing the relevance of the compound in the context of human diseases.

scholarly journals Systems Pharmacology Dissection of Traditional Chinese Medicine Wen-Dan Decoction for Treatment of Cardiovascular Diseases

2018 ◽  
Vol 2018 ◽  
pp. 1-14 ◽  
Author(s):  
Tao-Hua Lan ◽  
Lu-Lu Zhang ◽  
Yong-Hua Wang ◽  
Huan-Lin Wu ◽  
Dan-Ping Xu
Keyword(s):  
Chinese Medicine ◽  
Cardiovascular Diseases ◽  
Traditional Chinese Medicine ◽  
Molecular Mechanisms ◽  
Modern Medicine ◽  
System Level ◽  
Therapeutic Effects ◽  
Active Compounds ◽  
System Pharmacology ◽  
Underlying Mechanisms

Cardiovascular diseases (CVDs) have been recognized as first killer of human health. The underlying mechanisms of CVDs are extremely complicated and not fully revealed, leading to a challenge for CVDs treatment in modern medicine. Traditional Chinese medicine (TCM) characterized by multiple compounds and targets has shown its marked effects on CVDs therapy. However, system-level understanding of the molecular mechanisms is still ambiguous. In this study, a system pharmacology approach was developed to reveal the underlying molecular mechanisms of a clinically effective herb formula (Wen-Dan Decoction) in treating CVDs. 127 potential active compounds and their corresponding 283 direct targets were identified in Wen-Dan Decoction. The networks among active compounds, targets, and diseases were built to reveal the pharmacological mechanisms of Wen-Dan Decoction. A “CVDs pathway” consisted of several regulatory modules participating in therapeutic effects of Wen-Dan Decoction in CVDs. All the data demonstrates that Wen-Dan Decoction has multiscale beneficial activity in CVDs treatment, which provides a new way for uncovering the molecular mechanisms and new evidence for clinical application of Wen-Dan Decoction in cardiovascular disease.

scholarly journals High Cysteine Diet Reduces Insulin Resistance in SHR-CRP Rats

2021 ◽  
pp. 687-700
Author(s):  
J KRIJT ◽  
J SOKOLOVÁ ◽  
J ŠILHAVÝ ◽  
P MLEJNEK ◽  
J KUBOVČIAK ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Animal Studies ◽  
Serum Insulin ◽  
Body Fluids ◽  
Tissue Samples ◽  
Beneficial Effects ◽  
Fat Depots ◽  
Underlying Mechanisms ◽  
Similar Body

Increased plasma total cysteine (tCys) has been associated with obesity and metabolic syndrome in human and some animal studies but the underlying mechanisms remain unclear. In this study, we aimed at evaluating the effects of high cysteine diet administered to SHR-CRP transgenic rats, a model of metabolic syndrome and inflammation. SHR-CRP rats were fed either standard (3.2 g cystine/kg diet) or high cysteine diet (HCD, enriched with additional 4 g L-cysteine/kg diet). After 4 weeks, urine, plasma and tissue samples were collected and parameters of metabolic syndrome, sulfur metabolites and hepatic gene expression were evaluated. Rats on HCD exhibited similar body weights and weights of fat depots, reduced levels of serum insulin, and reduced oxidative stress in the liver. The HCD did not change concentrations of tCys in tissues and body fluids while taurine in tissues and body fluids, and urinary sulfate were significantly increased. In contrast, betaine levels were significantly reduced possibly compensating for taurine elevation. In summary, increased Cys intake did not induce obesity while it ameliorated insulin resistance in the SHR-CRP rats, possibly due to beneficial effects of accumulating taurine.

scholarly journals Integrated high-throughput small RNA and transcriptome sequencing unveil the shape-dependent toxicity of nano-alumina in rat astrocytes

2021 ◽  
Vol 33 (1) ◽  
Author(s):  
Yuanyuan Chen ◽  
Li Dong ◽  
Fuchang Deng ◽  
Yaqiang Cao ◽  
Yuanzheng Fu ◽  
...  
Keyword(s):  
Large Scale ◽  
Ex Vivo ◽  
Critical Role ◽  
Ether Lipid ◽  
Global Market ◽  
Alumina Nanoparticles ◽  
Nf Kappa B ◽  
Toxic Response ◽  
Nanoparticle Morphology ◽  
Underlying Mechanisms

Abstract Background The large-scale applications of alumina nanoparticles (Al2O3-NPs), one of the most important NPs in the global market, are causing severe damages to the environment and human health. Our previous research has revealed a critical role of nanoparticle morphology (e.g., flake and rod) in determining the toxic potencies of Al2O3-NPs, where nanorods demonstrated a significantly stronger toxic response than that of nanoflakes. However, their underlying mechanisms have not been completely elucidated yet. In the present study, we evaluated and compared the potential toxicological mechanisms of two shapes of γ-Al2O3-NPs (flake versus rod) by measuring miRNA and mRNA profiles of astrocytes in rat cerebral cortex, ex vivo. Results A total of 269 mRNAs and 122 miRNAs, 180 mRNAs and 116 miRNAs were differentially expressed after nanoflakes or nanorods exposure, respectively. Among them, 55 miRNAs (e.g., miR-760-5p, miR-326-3p, and miR-35) and 105 mRNAs (e.g., Kdm4d, Wdr62, and Rps6) showed the same trend between the two shapes. These miRNAs and mRNAs were mainly involved in apoptosis, inflammatory pathways (e.g., NF-kappa B), carcinogenic pathways (e.g., MAPK, p53, Notch, Rap1, and Ras), and cellular lipid metabolisms (e.g., glycerolipid metabolism, sphingolipid, and ether lipid metabolism). However, the remaining miRNAs and mRNAs either showed an opposite trend or only changed by a particular shape. Nanorods could specifically alter the changes of PI3K/Akt, AMPK and TNF pathways, cell cycle, and cellular senescence, while nanoflakes caused the changes of Toll and lmd signaling pathways. Conclusions Combined with previous research results, we further revealed the potential biomolecular mechanisms leading to the stronger toxicity of nanorods than that of nanoflakes, and multi-omics is a powerful approach to elucidate morphology-related mode of actions.

scholarly journals Role of the COP9 Signalosome (CSN) in Cardiovascular Diseases

Biomolecules ◽  
2019 ◽  
Vol 9 (6) ◽  
pp. 217 ◽  
Author(s):  
Milic ◽  
Tian ◽  
Bernhagen
Keyword(s):  
Cardiovascular Diseases ◽  
Molecular Mechanisms ◽  
Three Dimensional ◽  
Cell Types ◽  
Ubiquitin Proteasome System ◽  
Cop9 Signalosome ◽  
Ring E3 Ligase ◽  
Ubiquitin Proteasome ◽  
Underlying Mechanisms ◽  
Isopeptidase Activity

The constitutive photomorphogenesis 9 (COP9) signalosome (CSN) is an evolutionarily conserved multi-protein complex, consisting of eight subunits termed CSN1-CSN8. The main biochemical function of the CSN is the control of protein degradation via the ubiquitin-proteasome-system through regulation of cullin-RING E3-ligase (CRL) activity by deNEDDylation of cullins, but the CSN also serves as a docking platform for signaling proteins. The catalytic deNEDDylase (isopeptidase) activity of the complex is executed by CSN5, but only efficiently occurs in the three-dimensional architectural context of the complex. Due to its positioning in a central cellular pathway connected to cell responses such as cell-cycle, proliferation, and signaling, the CSN has been implicated in several human diseases, with most evidence available for a role in cancer. However, emerging evidence also suggests that the CSN is involved in inflammation and cardiovascular diseases. This is both due to its role in controlling CRLs, regulating components of key inflammatory pathways such as nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and complex-independent interactions of subunits such as CSN5 with inflammatory proteins. In this case, we summarize and discuss studies suggesting that the CSN may have a key role in cardiovascular diseases such as atherosclerosis and heart failure. We discuss the implicated molecular mechanisms ranging from inflammatory NF-κB signaling to proteotoxicity and necrosis, covering disease-relevant cell types such as myeloid and endothelial cells or cardiomyocytes. While the CSN is considered to be disease-exacerbating in most cancer entities, the cardiovascular studies suggest potent protective activities in the vasculature and heart. The underlying mechanisms and potential therapeutic avenues will be critically discussed.

scholarly journals The Gut Barrier, Intestinal Microbiota, and Liver Disease: Molecular Mechanisms and Strategies to Manage

2020 ◽  
Vol 21 (21) ◽  
pp. 8351
Author(s):  
Julio Plaza-Díaz ◽  
Patricio Solís-Urra ◽  
Fernando Rodríguez-Rodríguez ◽  
Jorge Olivares-Arancibia ◽  
Miguel Navarro-Oliveros ◽  
...  
Keyword(s):  
Liver Disease ◽  
Intestinal Microbiota ◽  
Animal Studies ◽  
Molecular Mechanisms ◽  
Bacterial Species ◽  
Intestinal Barrier ◽  
Lifestyle Changes ◽  
Alcoholic Fatty Liver ◽  
Underlying Mechanisms

Liver disease encompasses pathologies as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, alcohol liver disease, hepatocellular carcinoma, viral hepatitis, and autoimmune hepatitis. Nowadays, underlying mechanisms associating gut permeability and liver disease development are not well understood, although evidence points to the involvement of intestinal microbiota and their metabolites. Animal studies have shown alterations in Toll-like receptor signaling related to the leaky gut syndrome by the action of bacterial lipopolysaccharide. In humans, modifications of the intestinal microbiota in intestinal permeability have also been related to liver disease. Some of these changes were observed in bacterial species belonging Roseburia, Streptococcus, and Rothia. Currently, numerous strategies to treat liver disease are being assessed. This review summarizes and discusses studies addressed to determine mechanisms associated with the microbiota able to alter the intestinal barrier complementing the progress and advancement of liver disease, as well as the main strategies under development to manage these pathologies. We highlight those approaches that have shown improvement in intestinal microbiota and barrier function, namely lifestyle changes (diet and physical activity) and probiotics intervention. Nevertheless, knowledge about how such modifications are beneficial is still limited and specific mechanisms involved are not clear. Thus, further in-vitro, animal, and human studies are needed.

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