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Natural Products as Preventive or Therapeutic Tools for Angiogenesis Related Diseases

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Natural Products Chemistry".

Deadline for manuscript submissions: closed (30 November 2020) | Viewed by 26901

Special Issue Editor

Prof. Dr. Lucia Morbidelli

E-Mail Website
Guest Editor
Department of Life Science, Universita degli Studi di Siena, Siena, Italy
Interests: angiogenesis; endothelial cells; endothelial dysfunction; vasoactive mediators; gaseous transmitters; nutraceuticals; cardiovascular drugs; oxidative stress; inflammation; metabolic disorders; cardiovascular diseases; neurovascular diseases; ocular diseases; cancer; wound healing; tissue regeneration

Special Issue Information

Dear Colleagues,

Angiogenesis, the development of new vessels form pre-existing ones, is a prerequisite for the physiological growth, repair, and functioning of our organs, but also concurs in pathological conditions, where an inflammatory and oxidative condition exists in supporting angiogenesis deregulation, such as cancer, eye diseases, and chronic degenerative disorders. A correct angiogenesis and neovascular response also accompanies wound healing, interaction with biocompatible materials, and tissue regeneration. Last, but not least, is the role of endothelial functioning in the prevention of “inflammaging”, and the onset of cardiovascular/neurovascular pathologies typical of ageing.

As a result of the multiple roles of endothelium in these various physio-pathological conditions, the use of conventional drugs is often not enough to control disease development and evolution, thus requiring novel pharmacological tools to overcome inefficacy or resistance to approved drugs, or to satisfy unmet medical needs.

From the dawn of time, humans were able to discriminate toxic and beneficial products from nature, but our knowledge remains incomplete. Natural products deriving from microbial, plant, and animal organisms are able to prevent or cure various pathological conditions, and in this respect, nature can be the source of lead bioactive compounds or materials to be used in the prevention and therapy of various angiogenesis-dependent disorders. This Special Issue was designed to underpin the pivotal role of natural products in drug discovery for human diseases dependent on angiogenesis and endothelial functioning. An example is the use of nutraceuticals with antioxidant and anti-inflammatory activities as a preventive or therapeutic option in order to maintain an adequate vascularization and proper endothelial cell functioning. At the same time, some phytochemicals have been demonstrated to inhibit angiogenesis and to control tumor development.

Original research articles or reviews will aim to assess and report on the effects of natural products on biological targets (receptors, enzymes, transcription factors, etc.), or on multiple mechanisms ranging from general antioxidant and anti-inflammatory activities, to the more specific effects on endothelium. It is expected that the use of natural products (both crude preparations and isolated compounds) can be exploited as a preventive approach in the control of different pathologies, or as a therapeutic option in combination with approved drugs.

Prof. Dr. Lucia Morbidelli
Guest Editor

Manuscript Submission Information

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Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • angiogenesis
  • endothelial cells
  • endothelial dysfunction
  • vasoactive mediators
  • gaseous transmitters
  • nutraceuticals
  • cardiovascular drugs
  • oxidative stress
  • inflammation
  • metabolic disorders
  • cardiovascular diseases
  • neurovascular diseases
  • ocular disease
  • cancer
  • wound healing
  • tissue regeneration

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Published Papers (5 papers)

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Research

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11 pages, 1283 KiB  
Article
An Oily Fish Diet Improves Subclinical Inflammation in People at High Cardiovascular Risk: A Randomized Controlled Study
by Giuseppina Costabile, Giuseppe Della Pepa, Claudia Vetrani, Paola Vitaglione, Ettore Griffo, Rosalba Giacco, Marilena Vitale, Dominic Salamone, Angela Albarosa Rivellese, Giovanni Annuzzi and Lutgarda Bozzetto
Molecules 2021, 26(11), 3369; https://doi.org/10.3390/molecules26113369 - 2 Jun 2021
Cited by 5 | Viewed by 4151
Abstract
Interest has arisen on the anti-inflammatory action of dietary components, including long-chain n-3 fatty acids (LCn3) and polyphenols (PP). The aim of this study was to evaluate the effects of diets rich in PP and oily fish (high-LCn3 diets) on markers of subclinical [...] Read more.
Interest has arisen on the anti-inflammatory action of dietary components, including long-chain n-3 fatty acids (LCn3) and polyphenols (PP). The aim of this study was to evaluate the effects of diets rich in PP and oily fish (high-LCn3 diets) on markers of subclinical inflammation and growth factors in people at high cardiometabolic risk. Individuals with high waist circumference and one more component of metabolic syndrome were randomized to one of the following isoenergetic diets: low LCn3&PP, high LCn3, high PP, high LCn3&PP. Before and after 8 weeks, fasting and postprandial plasma concentrations of hs-CRP and fasting serum concentrations of IL-1, IL-4, IL-6, IL-10, IL-17, INF-, TNF-, FGF, VEGF, PDGF-, G-CSF, and GM-CSF were determined. An oily fish diet reduced fasting plasma hs-CRP (1.28 ± 12.0, −12.5 ± 6.9, 22.5 ± 33.6, −12.2 ± 11.9; 8-week percent change, Mean ± SEM; low LCn3&PP, high LCn3, high PP, high LCn3&PP group, respectively), postprandial 6h-AUC hs-CRP (4.6 ± 16.3, −18.2 ± 7.2, 26.9 ± 35.1, −11.5 ± 11.8, 8-week percent change) and fasting IL-6 (20.8 ± 18.7, −2.44 ± 12.4, 28.1 ± 17.4, −9.6 ± 10.2), IL-17 (2.40 ± 4.9, −13.3 ± 4.9, 3.8 ± 4.43, −11.5 ± 4.7), and VEGF (−5.7 ± 5.8, −5.6 ± 7.5, 3.5 ± 5.8, −11.1 ± 5.5) (8-week percent change; p < 0.05 for LCn3 effect for all; no significant effect for PP; 2-factor ANOVA). An oily fish diet improved subclinical inflammation, while no significant effect was observed for dietary polyphenols. Full article
(This article belongs to the Special Issue Natural Products as Preventive or Therapeutic Tools for Angiogenesis Related Diseases)
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14 pages, 2574 KiB  
Article
New Perspectives of S-Adenosylmethionine (SAMe) Applications to Attenuate Fatty Acid-Induced Steatosis and Oxidative Stress in Hepatic and Endothelial Cells
by Laura Vergani, Francesca Baldini, Mohamad Khalil, Adriana Voci, Pietro Putignano and Niccolò Miraglia
Molecules 2020, 25(18), 4237; https://doi.org/10.3390/molecules25184237 - 15 Sep 2020
Cited by 14 | Viewed by 3941
Abstract
S-adenosylmethionine (SAMe) is an endogenous methyl donor derived from ATP and methionine that has pleiotropic functions. Most SAMe is synthetized and consumed in the liver, where it acts as the main methylating agent and in protection against the free radical toxicity. Previous studies [...] Read more.
S-adenosylmethionine (SAMe) is an endogenous methyl donor derived from ATP and methionine that has pleiotropic functions. Most SAMe is synthetized and consumed in the liver, where it acts as the main methylating agent and in protection against the free radical toxicity. Previous studies have shown that the administration of SAMe as a supernutrient exerted many beneficial effects in various tissues, mainly in the liver. In the present study, we aimed to clarify the direct effects of SAMe on fatty acid-induced steatosis and oxidative stress in hepatic and endothelial cells. Hepatoma FaO cells and endothelial HECV cells exposed to a mixture of oleate/palmitate are reliable models for hepatic steatosis and endothelium dysfunction, respectively. Our findings indicate that SAMe was able to significantly ameliorate lipid accumulation and oxidative stress in hepatic cells, mainly through promoting mitochondrial fatty acid entry for β-oxidation and external triglyceride release. SAMe also reverted both lipid accumulation and oxidant production (i.e., ROS and NO) in endothelial cells. In conclusion, these outcomes suggest promising beneficial applications of SAMe as a nutraceutical for metabolic disorders occurring in fatty liver and endothelium dysfunction. Full article
(This article belongs to the Special Issue Natural Products as Preventive or Therapeutic Tools for Angiogenesis Related Diseases)
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19 pages, 3567 KiB  
Article
Piceatannol, a Natural Analog of Resveratrol, Exerts Anti-angiogenic Efficiencies by Blockage of Vascular Endothelial Growth Factor Binding to Its Receptor
by Wei-Hui Hu, Diana Kun Dai, Brody Zhong-Yu Zheng, Ran Duan, Tina Ting-Xia Dong, Qi-Wei Qin and Karl Wah-Keung Tsim
Molecules 2020, 25(17), 3769; https://doi.org/10.3390/molecules25173769 - 19 Aug 2020
Cited by 27 | Viewed by 4887
Abstract
Piceatannol is also named as trans-3,4,3′,5′-tetrahydroxy-stilbene, which is a natural analog of resveratrol and a polyphenol existing in red wine, grape and sugar cane. Piceatannol has been proved to possess activities of immunomodulatory, anti-inflammatory, antiproliferative and anticancer. However, the effect of piceatannol [...] Read more.
Piceatannol is also named as trans-3,4,3′,5′-tetrahydroxy-stilbene, which is a natural analog of resveratrol and a polyphenol existing in red wine, grape and sugar cane. Piceatannol has been proved to possess activities of immunomodulatory, anti-inflammatory, antiproliferative and anticancer. However, the effect of piceatannol on VEGF-mediated angiogenesis is not known. Here, the inhibitory effects of piceatannol on VEGF-induced angiogenesis were tested both in vitro and in vivo models of angiogenesis. In human umbilical vein endothelial cells (HUVECs), piceatannol markedly reduced the VEGF-induced cell proliferation, migration, invasion, as well as tube formation without affecting cell viability. Furthermore, piceatannol significantly inhibited the formation of subintestinal vessel in zebrafish embryos in vivo. In addition, we identified the underlying mechanism of piceatannol in triggering the anti-angiogenic functions. Piceatannol was proposed to bind with VEGF, thus attenuating VEGF in activating VEGF receptor and blocking VEGF-mediated downstream signaling, including expressions of phosphorylated eNOS, Erk and Akt. Furthermore, piceatannol visibly suppressed ROS formation, as triggered by VEGF. Moreover, we further determined the outcome of piceatannol binding to VEGF in cancer cells: piceatannol significantly suppressed VEGF-induced colon cancer proliferation and migration. Thus, these lines of evidence supported the conclusion that piceatannol could down regulate the VEGF-mediated angiogenic functions with no cytotoxicity via decreasing the amount of VEGF binding to its receptors, thus affecting the related downstream signaling. Piceatannol may be developed into therapeutic agents or health products to reduce the high incidence of angiogenesis-related diseases. Full article
(This article belongs to the Special Issue Natural Products as Preventive or Therapeutic Tools for Angiogenesis Related Diseases)
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Review

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14 pages, 2652 KiB  
Review
Flavonoid-Inspired Vascular Disrupting Agents: Exploring Flavone-8-Acetic Acid and Derivatives in the New Century
by Silvia Gobbi, Federica Belluti, Angela Rampa and Alessandra Bisi
Molecules 2021, 26(14), 4228; https://doi.org/10.3390/molecules26144228 - 12 Jul 2021
Cited by 12 | Viewed by 2757
Abstract
Naturally occurring flavonoids are found as secondary metabolites in a wide number of plants exploited for both medicine and food and have long been known to be endowed with multiple biological activities, making them useful tools for the treatment of different pathologies. Due [...] Read more.
Naturally occurring flavonoids are found as secondary metabolites in a wide number of plants exploited for both medicine and food and have long been known to be endowed with multiple biological activities, making them useful tools for the treatment of different pathologies. Due to the versatility of the scaffolds and the vast possibilities of appropriate decoration, they have also been regarded as fruitful sources of lead compounds and excellent chemical platforms for the development of bioactive synthetic compounds. Flavone-8-acetic acid (FAA) and 5,6-dimethylxanthone acetic acid (DMXAA) emerged for their antitumour potential due to the induction of cytokines and consequent rapid haemorrhagic necrosis of murine tumour vasculature, and different series of derivatives have been designed thereafter. Although the promising DMXAA failed in phase III clinical trials because of strict species-specificity, a boost in research came from the recent identification of the stimulator of interferon genes (STING), responsible for supporting tumoural innate immune responses, as a possible biological target. Consequently, in the last decade a renewal of interest for these flavonoid-based structures was noticed, and novel derivatives have been synthesised and evaluated for a deeper understanding of the molecular features needed for affecting human cells. Undoubtedly, these natural-derived molecules deserve further investigation and still appear attractive in an anticancer perspective. Full article
(This article belongs to the Special Issue Natural Products as Preventive or Therapeutic Tools for Angiogenesis Related Diseases)
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19 pages, 1301 KiB  
Review
Circulating Metabolites Originating from Gut Microbiota Control Endothelial Cell Function
by Amedeo Amedei and Lucia Morbidelli
Molecules 2019, 24(21), 3992; https://doi.org/10.3390/molecules24213992 - 5 Nov 2019
Cited by 55 | Viewed by 10568
Abstract
Cardiovascular functionality strictly depends on endothelial cell trophism and proper biochemical function. Any condition (environmental, pharmacological/toxicological, physical, or neuro-humoral) that changes the vascular endothelium has great consequences for the organism’s wellness and on the outcome and evolution of severe cardiovascular pathologies. Thus, knowledge [...] Read more.
Cardiovascular functionality strictly depends on endothelial cell trophism and proper biochemical function. Any condition (environmental, pharmacological/toxicological, physical, or neuro-humoral) that changes the vascular endothelium has great consequences for the organism’s wellness and on the outcome and evolution of severe cardiovascular pathologies. Thus, knowledge of the mechanisms, both endogenous and external, that affect endothelial dysfunction is pivotal to preventing and treating these disorders. In recent decades, significant attention has been focused on gut microbiota and how these symbiotic microorganisms can influence host health and disease development. Indeed, dysbiosis has been reported to be at the base of a range of different pathologies, including pathologies of the cardiovascular system. The study of the mechanism underlying this relationship has led to the identification of a series of metabolites (released by gut bacteria) that exert different effects on all the components of the vascular system, and in particular on endothelial cells. The imbalance of factors promoting or blunting endothelial cell viability and function and angiogenesis seems to be a potential target for the development of new therapeutic interventions. This review highlights the circulating factors identified to date, either directly produced by gut microbes or resulting from the metabolism of diet derivatives as polyphenols. Full article
(This article belongs to the Special Issue Natural Products as Preventive or Therapeutic Tools for Angiogenesis Related Diseases)
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