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Keywords = human iNOS (target) and eNOS

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22 pages, 4984 KB  
Article
Preparative Separation of Antioxidants from Sea Buckthorn and Its Antioxidant Activity In Vitro via Endothelial Function Regulation
by Yurong Cheng, Wenjuan Kang, Jingwen Hu, Xueru Fan, Xingmei Nan, Zonghao Zhang and Fang Yang
Int. J. Mol. Sci. 2026, 27(9), 3757; https://doi.org/10.3390/ijms27093757 - 23 Apr 2026
Viewed by 296
Abstract
Sea buckthorn, a homologue of medicine and food, contains a host of bioactives that can prevent many diseases, especially cardiovascular diseases. The association between oxidative stress (OS) and cardiovascular diseases (CVDs) has been well-established, with OS ultimately leading to CVDs through lipid peroxidation [...] Read more.
Sea buckthorn, a homologue of medicine and food, contains a host of bioactives that can prevent many diseases, especially cardiovascular diseases. The association between oxidative stress (OS) and cardiovascular diseases (CVDs) has been well-established, with OS ultimately leading to CVDs through lipid peroxidation and other mechanisms. In this study, antioxidant components were isolated from sea buckthorn by polyamide medium-pressure chromatography coupled with an HPLC-DPPH activity screening system. Two potential compounds were isolated and identified as Tetrahydroharmol and Isorhamnetin3-O-(6-O-E-sinapoyl)-β-D-glucopyranosyl-(1-2)-β-D-glucopyranoside-7-O-α-L-rhamnopyranoside. Molecular docking technology was used to explore the binding ability of two antioxidant active components to target proteins (LDH, SOD, Nrf2, iNOS, and eNOS). In addition, the antioxidant capacity was determined by EA.hy926 human umbilical vein endothelial fusion cell experiments. The results demonstrate the efficacy of this method for isolating high-purity antioxidants from sea buckthorn. These two activity compounds exhibit potential effects against cardiovascular diseases through antioxidant mechanisms. Full article
(This article belongs to the Section Molecular Biology)
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63 pages, 3510 KB  
Review
Morphometric and Molecular Interplay in Hypertension-Induced Cardiac Remodeling with an Emphasis on the Potential Therapeutic Implications
by Lyubomir Gaydarski, Kristina Petrova, Stancho Stanchev, Dimitar Pelinkov, Alexandar Iliev, Iva N. Dimitrova, Vidin Kirkov, Boycho Landzhov and Nikola Stamenov
Int. J. Mol. Sci. 2025, 26(9), 4022; https://doi.org/10.3390/ijms26094022 - 24 Apr 2025
Cited by 13 | Viewed by 4764
Abstract
Hypertension-induced cardiac remodeling is a complex process driven by interconnected molecular and cellular mechanisms that culminate in hypertensive myocardium, characterized by ventricular hypertrophy, fibrosis, impaired angiogenesis, and myocardial dysfunction. This review discusses the histomorphometric changes in capillary density, fibrosis, and mast cells in [...] Read more.
Hypertension-induced cardiac remodeling is a complex process driven by interconnected molecular and cellular mechanisms that culminate in hypertensive myocardium, characterized by ventricular hypertrophy, fibrosis, impaired angiogenesis, and myocardial dysfunction. This review discusses the histomorphometric changes in capillary density, fibrosis, and mast cells in the hypertensive myocardium and delves into the roles of key regulatory systems, including the apelinergic system, vascular endothelial growth factor (VEGF)/VEGF receptor (VEGFR) pathways, and nitric oxide (NO)/nitric oxide synthase (NOS) signaling in the pathogenesis of hypertensive heart disease (HHD). Capillary rarefaction, a hallmark of HHD, contributes to myocardial ischemia and fibrosis, underscoring the importance of maintaining vascular integrity. Targeting capillary density (CD) through antihypertensive therapy or angiogenic interventions could significantly improve cardiac outcomes. Myocardial fibrosis, mediated by excessive collagen deposition and influenced by fibroblast growth factor-2 (FGF-2) and transforming growth factor-beta (TGF-β), plays a pivotal role in the structural remodeling of hypertensive myocardium. While renin–angiotensin–aldosterone system (RAAS) inhibitors show anti-fibrotic effects, more targeted therapies are needed to address fibrosis directly. Mast cells, though less studied in humans, emerge as critical regulators of cardiac remodeling through their release of pro-fibrotic mediators such as histamine, tryptase, and FGF-2. The apelinergic system emerges as a promising therapeutic target due to its vasodilatory, anti-fibrotic, and cardioprotective properties. The system counteracts the deleterious effects of the RAAS and has demonstrated efficacy in preclinical models of hypertension-induced cardiac damage. Despite its potential, human studies on apelin analogs remain limited, warranting further exploration to evaluate their clinical utility. VEGF signaling plays a dual role, facilitating angiogenesis and compensatory remodeling during the early stages of arterial hypertension (AH) but contributing to maladaptive changes when dysregulated. Modulating VEGF signaling through exercise or pharmacological interventions has shown promise in improving CD and mitigating hypertensive cardiac damage. However, VEGF inhibitors, commonly used in oncology, can exacerbate AH and endothelial dysfunction, highlighting the need for therapeutic caution. The NO/NOS pathway is essential for vascular homeostasis and the prevention of oxidative stress. Dysregulation of this pathway, particularly endothelial NOS (eNOS) uncoupling and inducible NOS (iNOS) overexpression, leads to endothelial dysfunction and nitrosative stress in hypertensive myocardium. Strategies to restore NO bioavailability, such as tetrahydrobiopterin (BH4) supplementation and antioxidants, hold potential for therapeutic application but require further validation. Future studies should adopt a multidisciplinary approach to integrate molecular insights with clinical applications, paving the way for more personalized and effective treatments for HHD. Addressing these challenges will not only enhance the understanding of hypertensive myocardium but also improve patient outcomes and quality of life. Full article
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38 pages, 2181 KB  
Review
Is Inducible Nitric Oxide Synthase (iNOS) Promising as a New Target Against Pulmonary Hypertension?
by Piotr Ryszkiewicz, Eberhard Schlicker and Barbara Malinowska
Antioxidants 2025, 14(4), 377; https://doi.org/10.3390/antiox14040377 - 21 Mar 2025
Cited by 9 | Viewed by 5506
Abstract
Pulmonary hypertension (PH) is a progressive disease characterized by elevated blood pressure in the pulmonary arteries, associated also with inflammation and oxidative stress. Inducible nitric oxide synthase (iNOS) is one of the key mediators of inflammation and immune system activation. Although preclinical studies [...] Read more.
Pulmonary hypertension (PH) is a progressive disease characterized by elevated blood pressure in the pulmonary arteries, associated also with inflammation and oxidative stress. Inducible nitric oxide synthase (iNOS) is one of the key mediators of inflammation and immune system activation. Although preclinical studies mostly suggest a detrimental role of iNOS overactivation in PH, there is a lack of exhaustive analyses and summaries. Therefore, this literature overview aims to fill this gap. The involvement of iNOS in the pathogenesis of the four main clinical groups of PH is discussed to assess whether targeting iNOS could be a promising way to treat PH. iNOS expression patterns in the organs primarily affected by PH are analyzed both in animals and in humans. Consequently, the effectiveness of pharmacological iNOS inhibition and/or iNOS gene deletion is discussed and compared, also with reference to the activity of constitutive NOS isoforms, particularly endothelial NOS (eNOS). Overall, our overview suggests that selective iNOS inhibitors could be considered as a novel treatment strategy for PH, as decreases in right ventricular and pulmonary artery pressure, the alleviation of ventricular hypertrophy, and improvements of pulmonary and cardiac function were observed, among others. Nevertheless, further research efforts in this area are needed. Full article
(This article belongs to the Special Issue Nitric Oxide and Redox Mechanisms)
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26 pages, 36747 KB  
Article
Olea europea L. Leaves and Hibiscus sabdariffa L. Petals Extracts: Herbal Mix from Cardiovascular Network Target to Gut Motility Dysfunction Application
by Laura Beatrice Mattioli, Maria Frosini, Rosa Amoroso, Cristina Maccallini, Elda Chiano, Rita Aldini, Francesco Urso, Ivan Corazza, Matteo Micucci and Roberta Budriesi
Nutrients 2022, 14(3), 463; https://doi.org/10.3390/nu14030463 - 21 Jan 2022
Cited by 12 | Viewed by 5951
Abstract
It is well known that diet and nutrition play a critical role in the etiopathogenesis of many disorders. On the other hand, nutrients or bioactive compounds can specifically target and control various aspects of the mechanism underlying the pathology itself, and, in this [...] Read more.
It is well known that diet and nutrition play a critical role in the etiopathogenesis of many disorders. On the other hand, nutrients or bioactive compounds can specifically target and control various aspects of the mechanism underlying the pathology itself, and, in this context, diseases related to intestinal motility disorders stand out. The Herbal Mix (HM) consisting of Olea europea L. leaf (OEE) and Hibiscus sabdariffa L. (HSE) extracts (13:2) has been proven to be a promising nutraceutical option for many diseases, but its potential in inflammatory-driven gastrointestinal disorders is still unexplored. In this study, HM effects on guinea-pig ileum and colon contractility (induced or spontaneous) and on human iNOS activity, as well as on human colorectal adenocarcinoma Caco-2 cells, were studied. Results showed that the HM can control the ileum and colon contractility without blocking the progression of the food bolus, can selectively inhibit iNOS and possesses a strong pro-apoptotic activity towards Caco-2 cells. In conclusion, the present results suggest that, in some diseases, such as those related to motility disorders, an appropriate nutritional approach can be accompanied by a correct use of nutraceuticals that could help not only in ameliorating the symptoms but also in preventing more severe, cancer-related conditions. Full article
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