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A homogalacturonan from Lonicera japonica Thunb. disrupts angiogenesis via epidermal growth factor receptor and Delta-like 4 associated signaling

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Abstract

A homogeneous polysaccharide named as LJW2F2 was extracted and purified from the flowers of Lonicera japonica Thunb. Structural characteristic indicated that LJW2F2 was a homogalacturonan composed of α-1,4-D-galacturonic acid with a molecular weight of 7.2 kDa. Previous investigation suggested that homogalacturonan might impede angiogenesis, however the mechanism is still vague. Here we reported that LJW2F2 significantly disrupted capillary-like tube formation of human microvascular endothelia cells (HMEC-1) on matrigel as well as the cells migration. Mechanism study revealed that LJW2F2 might inactivate phosphorylation of epidermal growth factor receptor (EGFR), subsequently suppress Raf, mitogen-activated protein kinase (MEK) and extracellular-related kinase (ERK) phosphorylation. Moreover, LJW2F2 markedly decreased the expression of Notch1 and Delta-like ligand 4 (Dll4). Therefore, our results suggested that LJW2F2 might be a potential angiogenesis inhibitor via disturbing multiple signaling pathways.

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All data generated or analyzed involved in this study are included in the present manuscript.

Abbreviations

HMEC-1:

human microvascular endothelial cells

DMSO:

dimethyl sulfoxide

GC:

gas chromatography

HPGPC:

high performance gel permeation chromatography

NMR:

nuclear magnetic resonance

cDNA:

complementary DNA

EGF:

epidermal growth factor

HRP:

horseradish peroxidase

RT-PCR:

reverse transcription-PCR

ERK:

extracellular signal-regulated kinase

VEGF:

vascular endothelial growth factor

Dll4:

Delta-like 4

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Funding

This work was supported by National Key R&D Program of China (2019YFC1711000), Shanghai Municipal Science and Technology Major Project, National Natural Science Foundation of China (31870801), Kan Ding.

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Authors and Affiliations

  1. Glycochemistry and Glycobiology Lab, CAS Key Laboratory of Receptor Research, State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 555 Zu Chong Zhi Road, 201203, Shanghai, P. R. China

    Wenfeng Liao, Xiaodong Hu, Zhenyun Du, Peipei Wang & Kan Ding

  2. University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, P. R. of China

    Wenfeng Liao, Xiaodong Hu, Zhenyun Du & Kan Ding

  3. College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, P. R. of China

    Peipei Wang

  4. Zhongshan Institute for Drug Discovery, Shanghai Institute of Materia Medica, hinese Academy of Science, SSIP Healthcare and Medicine Demonstration Zone, Zhongshan Tsuihang New District, 528400, Zhongshan, P. R. of China

    Kan Ding

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  1. Wenfeng Liao
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  2. Xiaodong Hu
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  3. Zhenyun Du
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  4. Peipei Wang
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  5. Kan Ding
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Contributions

WL conducted all the biological experiment and drafted the manuscript; KD designed the experiments and revised the manuscript; PW supervised the research and reviewed the manuscript; XH performed the extraction and purification of polysaccharide; ZD carried out the statistical analyses.

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Correspondence to Peipei Wang or Kan Ding.

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Highlights

• The structure of a novel polysaccharide from Lonicera japonica is elucidated.

• The polysaccharide is a homogalacturan composing of α-1,4-D-galacturonic acid.

• The polysaccharide might inhibit HMEC-1 cells tube formation and migration.

• The polysaccharide could disrupt EGFR/Raf/MEK/ERK and Dll4-Notch1 signaling axis.

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Liao, W., Hu, X., Du, Z. et al. A homogalacturonan from Lonicera japonica Thunb. disrupts angiogenesis via epidermal growth factor receptor and Delta-like 4 associated signaling. Glycoconj J 39, 725–735 (2022). https://doi.org/10.1007/s10719-022-10088-2

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