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

Wenfeng Liao; Xiaodong Hu; Zhenyun Du; Peipei Wang; Kan Ding

doi:10.1007/s10719-022-10088-2

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

Glycoconj J. 2022 Dec;39(6):725-735. doi: 10.1007/s10719-022-10088-2. Epub 2022 Oct 28.

Authors

Wenfeng Liao^{1

2}, Xiaodong Hu^{1

2}, Zhenyun Du^{1

2}, Peipei Wang^{3

4}, Kan Ding^{5

6

7}

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.
² University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, P. R. of China.
³ 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. ppwang@shou.edu.cn.
⁴ College of Food Science and Technology, Shanghai Ocean University, Shanghai, 201306, P. R. of China. ppwang@shou.edu.cn.
⁵ 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. dingkan@simm.ac.cn.
⁶ University of Chinese Academy of Sciences, No. 19A Yuquan Road, Beijing, 100049, P. R. of China. dingkan@simm.ac.cn.
⁷ 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. dingkan@simm.ac.cn.

PMID: 36306024
DOI: 10.1007/s10719-022-10088-2

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.

Keywords: Angiogenesis; Dll4/Notch1 signaling; EGFR/Raf/MEK/ERK signaling cascade; Homogalacturonan; Lonicera japonica.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

ErbB Receptors / analysis
Flowers / chemistry
Humans
Lonicera* / chemistry
Polysaccharides / chemistry
Signal Transduction

Substances

ErbB Receptors
Polysaccharides