Harnessing polyphenol power by targeting eNOS for vascular diseases

Das, Mamali; Devi, Kasi Pandima; Belwal, Tarun; Devkota, Hari Prasad; Tewari, Devesh; Sahebnasagh, Adeleh; Nabavi, Seyed Fazel; Kashani, Hamid Reza Khayat; Rasekhian, Mahsa; Xu, Suowen; Amirizadeh, Mehran; Amini, Kourosh; Banach, Maciej; Xiao, Jianbo; Aghaabdollahian, Safieh; Nabavi, Seyed Mohammad

doi:10.1080/10408398.2021.1971153

Cited by 17 publications

(14 citation statements)

References 283 publications

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“…The net effect is that oxLDL increased the production of superoxide anion and inhibited endothelium-dependent vasodilation. The activity of eNOS is positively regulated by the phosphorylation of Ser1177, while the Thr495 phosphorylation inhibits eNOS activation ( 53 ). In addition, related studies have shown that HSP90 can bind to eNOS, and induce its coupling and thus produce NO.…”

Section: Oxldl and Endothelial Cell Dysfunctionmentioning

confidence: 99%

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Jiang

Zhou

Nabavi³

et al. 2022

Front. Cardiovasc. Med.

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104

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Atherosclerosis is an immuno-metabolic disease involving chronic inflammation, oxidative stress, epigenetics, and metabolic dysfunction. There is compelling evidence suggesting numerous modifications including the change of the size, density, and biochemical properties in the low-density lipoprotein (LDL) within the vascular wall. These modifications of LDL, in addition to LDL transcytosis and retention, contribute to the initiation, development and clinical consequences of atherosclerosis. Among different atherogenic modifications of LDL, oxidation represents a primary modification. A series of pathophysiological changes caused by oxidized LDL (oxLDL) enhance the formation of foam cells and atherosclerotic plaques. OxLDL also promotes the development of fatty streaks and atherogenesis through induction of endothelial dysfunction, formation of foam cells, monocyte chemotaxis, proliferation and migration of SMCs, and platelet activation, which culminate in plaque instability and ultimately rupture. This article provides a concise review of the formation of oxLDL, enzymes mediating LDL oxidation, and the receptors and pro-atherogenic signaling pathways of oxLDL in vascular cells. The review also explores how oxLDL functions in different stages of endothelial dysfunction and atherosclerosis. Future targeted pathways and therapies aiming at reducing LDL oxidation and/or lowering oxLDL levels and oxLDL-mediated pro-inflammatory responses are also discussed.

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Section: Oxldl and Endothelial Cell Dysfunctionmentioning

confidence: 99%

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Jiang

Zhou

Nabavi³

et al. 2022

Front. Cardiovasc. Med.

Self Cite

104

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“…The significant keywords in the early stages (2014-2017) included NF-κB, antioxidant response, HO-1, and gene expression. Over recent years (2019)(2020)(2021)(2022), ARE, ROS, particulate matter, obesity, vascular inflammation and mitochondrial dysfunction have been the main research hotspots. The collective findings validate the beneficial effects of Nrf2 against CVDs, supporting the development of naturally occurring Nrf2 agonists as promising therapeutic approach.…”

Section: Frontiers and Hotspotsmentioning

confidence: 99%

“…, generating peroxynitrite (ONOO − ), thereby inducing endothelial cell damage ( Hahner et al, 2020 ; Ogboo et al, 2022 ). In addition, uncoupled eNOS contributes to the generation of O 2 .- and ONOO − , leading to impairment of endothelial function and initiation of AS ( Das et al, 2021 ).…”

Section: Role Of Nrf2 Signaling In Cvdsmentioning

confidence: 99%

Activation of Nrf2 signaling: A key molecular mechanism of protection against cardiovascular diseases by natural products

Wei

Yang

et al. 2022

Front. Pharmacol.

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Cardiovascular diseases (CVD) are a group of cardiac and vascular disorders including myocardial ischemia, congenital heart disease, heart failure, hypertension, atherosclerosis, peripheral artery disease, rheumatic heart disease, and cardiomyopathies. Despite considerable progress in prophylaxis and treatment options, CVDs remain a leading cause of morbidity and mortality and impose an extremely high socioeconomic burden. Oxidative stress (OS) caused by disequilibrium in the generation of reactive oxygen species plays a crucial role in the pathophysiology of CVDs. Nuclear erythroid 2-related factor 2 (Nrf2), a transcription factor of endogenous antioxidant defense systems against OS, is considered an ideal therapeutic target for management of CVDs. Increasingly, natural products have emerged as a potential source of Nrf2 activators with cardioprotective properties and may therefore provide a novel therapeutic tool for CVD. Here, we present an updated comprehensive summary of naturally occurring products with cardioprotective properties that exert their effects by suppression of OS through activation of Nrf2 signaling, with the aim of providing useful insights for the development of therapeutic strategies exploiting natural products.

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“…PPs are a diverse category of plant secondary metabolites, displayed health-promoting properties, and are marketed as dietary supplements ( 338 , 344 , 345 ). Originally, PPs are defensive metabolites in plants secreted in response to abiotic and biotic tensions ( 346 ).…”

Section: General Overview Of Pps Chemistrymentioning

confidence: 99%

“…It is now well established that the regular consumption of PPs and/or PPs-rich foods are linked to a healthy lifestyle ( 347 – 349 ). To date, the chemical structure of more than 8,000 PPs has been characterized, and the emerging evidence suggests that global demands for PPs-rich foods (or supplements) have increased over the past decades ( 344 , 347 ).…”

Section: General Overview Of Pps Chemistrymentioning

confidence: 99%

May phytophenolics alleviate aflatoxins-induced health challenges? A holistic insight on current landscape and future prospects

2022

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The future GCC-connected environmental risk factors expedited the progression of nCDs. Indeed, the emergence of AFs is becoming a global food security concern. AFs are lethal carcinogenic mycotoxins, causing damage to the liver, kidney, and gastrointestinal organs. Long-term exposure to AFs leads to liver cancer. Almost a variety of food commodities, crops, spices, herbaceous materials, nuts, and processed foods can be contaminated with AFs. In this regard, the primary sections of this review aim to cover influencing factors in the occurrence of AFs, the role of AFs in progression of nCDs, links between GCC/nCDs and exposure to AFs, frequency of AFs-based academic investigations, and world distribution of AFs. Next, the current trends in the application of PPs to alleviate AFs toxicity are discussed. Nearly, more than 20,000 published records indexed in scientific databases have been screened to find recent trends on AFs and application of PPs in AFs therapy. Accordingly, shifts in world climate, improper infrastructures for production/storage of food commodities, inconsistency of global polices on AFs permissible concentration in food/feed, and lack of the public awareness are accounting for a considerable proportion of AFs damages. AFs exhibited their toxic effects by triggering the progression of inflammation and oxidative/nitrosative stress, in turn, leading to the onset of nCDs. PPs could decrease AFs-associated oxidative stress, genotoxic, mutagenic, and carcinogenic effects by improving cellular antioxidant balance, regulation of signaling pathways, alleviating inflammatory responses, and modification of gene expression profile in a dose/time-reliant fashion. The administration of PPs alone displayed lower biological properties compared to co-treatment of these metabolites with AFs. This issue might highlight the therapeutic application of PPs than their preventative content. Flavonoids such as quercetin and oxidized tea phenolics, curcumin and resveratrol were the most studied anti-AFs PPs. Our literature review clearly disclosed that considering PPs in antioxidant therapies to alleviate complications of AFs requires improvement in their bioavailability, pharmacokinetics, tissue clearance, and off-target mode of action. Due to the emergencies in the elimination of AFs in food/feedstuffs, further large-scale clinical assessment of PPs to decrease the consequences of AFs is highly required.

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Harnessing polyphenol power by targeting eNOS for vascular diseases

Cited by 17 publications

References 283 publications

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Mechanisms of Oxidized LDL-Mediated Endothelial Dysfunction and Its Consequences for the Development of Atherosclerosis

Activation of Nrf2 signaling: A key molecular mechanism of protection against cardiovascular diseases by natural products

May phytophenolics alleviate aflatoxins-induced health challenges? A holistic insight on current landscape and future prospects

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