Marine Natural Products as Angiogenesis Modulators

A special issue of Marine Drugs (ISSN 1660-3397).

Deadline for manuscript submissions: closed (31 December 2021) | Viewed by 7136

Special Issue Editor


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Guest Editor
School of Pharmacy, University of California, San Francisco, CA, USA

Special Issue Information

Dear Colleagues,

Angiogenesis is a process by which new blood vessels are produced from the existing blood vessels, and it plays an important role in development and tissue regeneration. However, uncontrolled angiogenesis can cause various diseases including coronary artery disease, stroke, age-related macular degeneration, rheumatoid arthritis, cancer, etc. Marine natural products have been considered a valuable source for drug discovery because of their chemical diversity and biological activities.

Manuscripts/reviews regarding marine natural products with anti/pro-angiogenic activities will be invited.

Dr. Donghwa Kim
Guest Editor

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Keywords

  • Angiogenesis
  • Vascular disease
  • VEGF signaling
  • TGF-beta signaling
  • Marine natural product

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Published Papers (2 papers)

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Research

11 pages, 1930 KiB  
Article
Largazole Inhibits Ocular Angiogenesis by Modulating the Expression of VEGFR2 and p21
by Beiying Qiu, Alison Tan, Yu Zhi Tan, Qi-Yin Chen, Hendrik Luesch and Xiaomeng Wang
Mar. Drugs 2021, 19(8), 471; https://doi.org/10.3390/md19080471 - 22 Aug 2021
Cited by 5 | Viewed by 2992
Abstract
Ocular angiogenic diseases, characterized by abnormal blood vessel formation in the eye, are the leading cause of blindness. Although Anti-VEGF therapy is the first-line treatment in the market, a substantial number of patients are refractory to it or may develop resistance over time. [...] Read more.
Ocular angiogenic diseases, characterized by abnormal blood vessel formation in the eye, are the leading cause of blindness. Although Anti-VEGF therapy is the first-line treatment in the market, a substantial number of patients are refractory to it or may develop resistance over time. As uncontrolled proliferation of vascular endothelial cells is one of the characteristic features of pathological neovascularization, we aimed to investigate the role of the class I histone deacetylase (HDAC) inhibitor Largazole, a cyclodepsipeptide from a marine cyanobacterium, in ocular angiogenesis. Our study showed that Largazole strongly inhibits retinal vascular endothelial cell viability, proliferation, and the ability to form tube-like structures. Largazole strongly inhibits the vessel outgrowth from choroidal explants in choroid sprouting assay while it does not affect the quiescent choroidal vasculature. Largazole also inhibits vessel outgrowth from metatarsal bones in metatarsal sprouting assay without affecting pericytes coverage. We further demonstrated a cooperative effect between Largazole and an approved anti-VEGF drug, Alflibercept. Mechanistically, Largazole strongly inhibits the expression of VEGFR2 and leads to an increased expression of cell cycle inhibitor, p21. Taken together, our study provides compelling evidence on the anti-angiogenic role of Largazole that exerts its function through mediating different signaling pathways. Full article
(This article belongs to the Special Issue Marine Natural Products as Angiogenesis Modulators)
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22 pages, 8958 KiB  
Article
Influence of Fucoidan Extracts from Different Fucus Species on Adult Stem Cells and Molecular Mediators in In Vitro Models for Bone Formation and Vascularization
by Fanlu Wang, Yuejun Xiao, Sandesh Neupane, Signe Helle Ptak, Ramona Römer, Junyu Xiong, Julia Ohmes, Andreas Seekamp, Xavier Fretté, Susanne Alban and Sabine Fuchs
Mar. Drugs 2021, 19(4), 194; https://doi.org/10.3390/md19040194 - 29 Mar 2021
Cited by 18 | Viewed by 3222
Abstract
Fucoidans, sulfated polysaccharides extracted from brown algae, are marine products with the potential to modulate bone formation and vascularization processes. The bioactivity and safety of fucoidans are highly associated with their chemical structure, which may vary with algae species and extraction method. Thus, [...] Read more.
Fucoidans, sulfated polysaccharides extracted from brown algae, are marine products with the potential to modulate bone formation and vascularization processes. The bioactivity and safety of fucoidans are highly associated with their chemical structure, which may vary with algae species and extraction method. Thus, in depth evaluation of fucoidan extracts in terms of endotoxin content, cytotoxicity, and their detailed molecular biological impact on the individual cell types in bone is needed. In this study, we characterized fucoidan extracts from three different Fucus species including Fucus vesiculosus (Fv), Fucus serratus (Fs), and Fucus distichus subsp. evanescens (Fe) for their chemical features, endotoxin content, cytotoxicity, and bioactive effects on human outgrowth endothelial cells (OEC) and human mesenchymal stem cells (MSC) as in vitro models for bone function and vascularization. Extracts contained mainly high molecular weight (HMW) fucoidans and were free of endotoxins that may cause inflammation or influence vascularization. OEC tolerated fucoidan concentrations up to 200 µg/mL, and no indication of cytotoxicity was observed. The inflammatory response, however, investigated by real-time PCR (RT-PCR) and enzyme-linked immunosorbent assay (ELISA) and endothelial barrier assessed by impedance measurement differed for the individual extracts. MSC in comparison with endothelial cells were more sensitive to fucoidans and showed partly reduced metabolic activity and proliferation at higher doses of fucoidans. Further results for MSC indicated impaired osteogenic functions in alkaline phosphatase and calcification assays. All tested extracts consistently lowered important molecular mediators involved in angiogenesis, such a VEGF (vascular endothelial growth factor), ANG-1 (angiopoietin 1), and ANG-2 (angiopoietin 2), as indicated by RT-PCR and ELISA. This was associated with antiangiogenic effects at the functional level using selected extracts in co-culture models to mimic bone vascularization processes during bone regeneration or osteosarcoma. Full article
(This article belongs to the Special Issue Marine Natural Products as Angiogenesis Modulators)
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