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New Publications on Endothelial Dysfunction Treatment with Plants and Natural Compounds, Plus Links

to Air Pollution and Coronary Spasm

Planta Med. 2018 Jan 17. doi: 10.1055/s-0044-100398. [Epub ahead of print] Phenolic Compounds as Arginase Inhibitors: New Insights Regarding Endothelial Dysfunction Treatment. Minozzo BR1, Fernandes D2, Beltrame FL1. Author information 1Department of Pharmaceutical Sciences, State University of Ponta Grossa, Ponta Grossa, Paraná, Brazil.2Department of Pharmacology, Federal University of Santa Catarina, Florianópolis, Santa Catarina, Brazil. Abstract Endothelial dysfunction is characterised by the low bioavailability of nitric oxide with a relevant negative impact on the nitric oxide/cGMP pathway. The loss of nitric oxide/cGMP signaling may be caused by an increased arginase activity. Plant-derived substances, especially polyphenols, are compounds that have the potential to inhibit arginase activity and they may represent an attractive therapeutic option to combat clinical outcomes related to endothelial dysfunction. An extensive review was carried out using all available data published in English in the Pubmed database, and without restriction regarding the year of publication. Despite the increased number of new substances that have been tested as arginase inhibitors, it is rare to find a compound that satisfies all the toxicological criteria to be used in the development of a new drug. On the other hand, recent data have shown that substances from plants have great potential to be applied as arginase inhibitors, most of which are polyphenols. Of the relevant mechanisms in this process, the inhibition of arginase by natural products seems to act against endothelial dysfunction by reestablishing the vascular function and elevating nitric oxide levels (by increasing the amounts of substrate (L-arginine, and endothelial nitric oxide synthase activation and stabilisation) as well as decreasing the generation of reactive species (formed by uncoupledendothelial nitric oxide synthase). This review summarises several topics regarding arginase inhibition by natural substances as well as indicating this pathway as an emergent strategy to elevate nitric oxide levels in disorders involving endothelialdysfunction. In addition, some aspects regarding structural activity and future perspectives are discussed. Eur J Nutr. 2018 Jan 12. doi: 10.1007/s00394-018-1611-7. [Epub ahead of print] Coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone improves postprandial endothelial dysfunction in patients with borderline and stage 1 hypertension. Kajikawa M1, Maruhashi T2, Hidaka T2, Nakano Y2, Kurisu S2, Matsumoto T2, Iwamoto Y2, Kishimoto S2, Matsui S2, Aibara Y3, Yusoff FM3, Kihara Y2, Chayama K4, Goto C5, Noma K1,3, Nakashima A3, Watanabe T6, Tone H6, Hibi M6, Osaki N6, Katsuragi Y6, Higashi Y7,8. Author information 1Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan.2Department of Cardiovascular Medicine, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.3Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan.4Department of Gastroenterology and Metabolism, Graduate School of Biomedical and Health Sciences, Hiroshima University, Hiroshima, Japan.5Department of Physical Therapy, Hiroshima International University, Hiroshima, Japan.6Health Care Food Research Laboratories, Kao Corporation, Tokyo, Japan.7Division of Regeneration and Medicine, Medical Center for Translational and Clinical Research, Hiroshima University Hospital, Hiroshima, Japan. yhigashi@hiroshima-u.ac.jp.8Department of Cardiovascular Regeneration and Medicine, Research Institute for Radiation Biology and Medicine (RIRBM), Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan. yhigashi@hiroshima-u.ac.jp. Abstract PURPOSE: The purpose of this study was to evaluate acute effects of coffee with a high content of chlorogenic acids and different hydroxyhydroquinone contents on postprandial endothelial dysfunction. METHODS: This was a single-blind, randomized, placebo-controlled, crossover-within-subject clinical trial. A total of 37 patients with borderline or stage 1 hypertension were randomized to two study groups. The participants consumed a test meal with a single intake of the test coffee. Subjects in the Study 1 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or coffee with a high content of chlorogenic acids and a high content of hydroxyhydroquinone with crossover. Subjects in the Study 2 group were randomized to single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone or placebo coffee with crossover. Endothelial function assessed by flow-mediated vasodilation and plasma concentration of 8-isoprostanes were measured at baseline and at 1 and 2 h after coffee intake. RESULTS: Compared with baseline values, single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone, but not coffee with a high content of chlorogenic acids and high content of hydroxyhydroquinone or placebo coffee, significantly improved postprandial flow-mediated vasodilation and decreased circulating 8-isoprostane levels. CONCLUSIONS: These findings suggest that a single intake of coffee with a high content of chlorogenic acids and low content of hydroxyhydroquinone is effective for improving postprandial endothelial dysfunction. CLINICAL TRIAL REGISTRATION: URL for Clinical Trial: https://upload.umin.ac.jp ; Registration Number for Clinical Trial: UMIN000013283. KEYWORDS: Atherosclerosis; Chlorogenic acids; Endothelial function; Hydroxyhydroquinone Coron Artery Dis. 2018 Jan 12. doi: 10.1097/MCA.0000000000000603. [Epub ahead of print] The association of chronic air pollutants with coronary artery spasm, vasospastic angina, and endothelial dysfunction. Choi BG1, Lee J2, Kim SW2, Lee MW2, Baek MJ3, Ryu YG3, Choi SY1, Byun JK1, Mashaly A4, Park Y4, Jang WY4, Kim W4, Choi JY4, Park EJ4, Na JO4, Choi CU4, Lim HE4, Kim EJ4, Park CG4, Seo HS4, Oh DJ4, Rha SW4. Author information 1Departments of Medicine.2Integrated Biomedical and Life Sciences.3Thoracic and Cardiovascular Surgery, Korea University Graduate School.4Cardiovascular Center, Korea University Guro Hospital, Seoul, Korea. Abstract BACKGROUND: We evaluated the effect of chronic exposure to air pollutants (APs) on coronary endothelial function and significant coronary artery spasm (CAS) as assessed by intracoronary acetylcholine (ACH) provocation test. PATIENTS AND METHODS: A total of 6430 patients with typical or atypical chest pain who underwent intracoronary ACH provocation test were enrolled. We obtained data on APs from the Korean National Institute of Environmental Research (http://www.nier.go.kr/). APs are largely divided into two types: particulate matter with aerodynamic diameter of less than or equal to 10 µm in size (PM10) and gaseous pollutants such as nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone. The primary endpoint is the incidence of significant CAS and its associated parameters during ACH provocation test. RESULTS: The incidence of CAS was positively correlated with an exposure duration of PM10, whereas nitrogen dioxide, sulfur dioxide, carbon monoxide, and ozone were shown to be unrelated to CAS. During the ACH provocation test, as PM10 increased, the frequency of CAS was increased, and the incidence of transient ST-segment elevation was also increased. There was a trend toward higher incidence of spontaneous spasm as PM10 increased. The mean exposure level of PM10 was 51.3±25.4 µg/m. The CAS risk increased by 4% when the level of PM10 increased by 20 µg/m by an adjusted Cox regression analysis. CONCLUSION: CAS incidence is closely related to exposure to PMs but not to gaseous pollutants. Particularly, higher exposure concentrations and longer exposure duration of PM10 increased the risk of CAS. These important findings provide a plausible mechanism that links air pollution to vasospastic angina and provide new insights into environmental factors. Evid Based Complement Alternat Med. 2017;2017:1021284. doi: 10.1155/2017/1021284. Epub 2017 Nov 28. The Vasodilatory Effects of Anti-Inflammatory Herb Medications: A Comparison Study of Four Botanical Extracts. Zhang HP1,2, Zhang DD2, Ke Y3, Bian K4,5. Author information 1National Clinical Research Base of Traditional Chinese Medicine, The Affiliated Hospital of Traditional Chinese Medicine of Xinjiang Medical University, Urumqi 830011, China.2Murad Research Institute for Modernized Chinese Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.3Teaching Experimental Center, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.4Department of Biochemistry and Molecular Medicine, George Washington University, Washington, DC 20052, USA.5George Washington Cancer Center, Washington, DC 20052, USA. Abstract Inflammation plays a pivotal role in the development and progression of cardiovascular diseases, in which, the endothelium dysfunction has been a key element. The current study was designed to explore the vasodilatory effect of anti-inflammatory herbs which have been traditionally used in different clinical applications. The total saponins from Actinidia arguta radix (SAA), total flavonoids from Glycyrrhizaeradix et rhizoma (FGR), total coumarins from Peucedani radix (CPR), and total flavonoids from Spatholobi caulis (FSC) were extracted. The isometric measurement of vasoactivity was used to observe the effects of herbal elements on the isolated aortic rings with or without endothelium. To understand endothelium-independent vasodilation, the effects of herb elements on agonists-induced vasocontractility and on the contraction of endothelium-free aortic rings exposed to a Ca2+-free medium were examined. Furthermore, the role of nitric oxide signaling in endothelium-dependent vasodilation was also evaluated. In summary, FGR and FSC exhibit potent anti-inflammatory effects compared to CPR and SAA. FGR exerts the strongest vasodilatory effect, while CPR shows the least. The relaxation induced by SAA and FSC required intact endothelia. The mechanism of this vasodilation might involve eNOS. CPR-mediated vasorelaxation appears to involve interference with intracellular calcium homeostasis, blocking Ca2+ influx or releasing intracellular Ca2+.

Endothelial Function Scientific Update Sponsored by Endothelix Inc.

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