Total saponins of panaxnotoginseng promotes lymphangiogenesis by activation VEGF-C expression of lymphatic endothelial cells

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• 作者：Jinlong Li^a ; ^{phjod@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yan Chen^a ; ^{952026015@qq.com" class="auth_mail" title="E-mail the corresponding author} ; Li Zhang^a ; ^{15221152917@163.com" class="auth_mail" title="E-mail the corresponding author} ; Lianping Xing^b ; ^c ; ^{Lianping_xing@urmc.rochester.edu" class="auth_mail" title="E-mail the corresponding author} ; Hao Xu^a ; ^{hoxu@163.com" class="auth_mail" title="E-mail the corresponding author} ; Yongjun Wang^a ; ^{yjwang8888@126.com" class="auth_mail" title="E-mail the corresponding author} ; Qi Shi^a ; ^{jzyjs200032@126.com" class="auth_mail" title="E-mail the corresponding author} ; Qianqian Liang^a ; ^{liangqianqiantcm@126.com" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Dimethyl sulfoxide (DMSO) (PubChem CID ; 679) ; MAZ51 ; VEGF Receptor 3 Kinase inhibitor (PubChemCID ; 9839842) ; Ethanol (PubChem CID ; 702) ; Chloroform (PubChemCID ; 6212) ; Methanol (PubChemCID ; 887) ; Acrylamide (PubChemCID ; 6579) ; Ammonium Persulfate (PubChemCID ; 62648) ; Glycine (PubChemCID ; 750) ; Sodium chloride (PubChemCID ; 5234) ; PD98059 (PubChemCID ; 4713) ; Wortmannin (PubChemCID ; 312145) ; SB203580 (PubChemCID ; 176155) ; SP600125 (PubChemCID ; 8515)
• 刊名：Journal of Ethnopharmacology
• 出版年：2016
• 出版时间：4 December 2016
• 年：2016
• 卷：193
• 期：Complete
• 页码：293-302
• 全文大小：2117 K

文摘

Lymphatic system plays an important role in maintaining the fluid homeostasis and normal immune responses, anatomic or functional obstruction of which leads to lymphedema, and treatments for therapeutic lymphangiogenesis are efficiency for secondary lymphedema. Total saponins of panaxnotoginseng (PNS) are a mixture isolated from Panaxnotoginseng (Burkill) F.H.Chen, which has been used as traditional Chinese medicine in China for treatment of cardio- and cerebro-vascular diseases. The aim of this study was to determine the effect and mechanism of PNS on lymphangiogenesis.

Methods

The Tg (fli1: egfp; gata1: dsred) transgenic zebrafish embryos were treated with different concentrations of PNS (10, 50, 100 μM) for 48 h with or without the 6 h pretreatment of the 30 μM Vascular endothelial growth factors receptor (VEGFR)-3 kinase inhibitor, followed with morphological observation and lympangiogenesis of thoracic duct assessment. The effect of PNS on cell viability, migration, tube formation and Vascular endothelial growth factors (VEGF)-C mRNA and protein expression of lymphatic endothelial cells (LECs) were determined. The role of phosphatidylinositol-3 (PI-3)-kinase (PI3K), extracellular signal-regulated kinase (ERK)1/2 pathways, c-Jun N-terminal kinase (JNK) and P38 mitogen activated protein kinases (MAPK) signaling in PNS-induced VEGF-C expression of LECs by using pharmacological agents to block each signal.

Results

PNS promotes lymphangiogenesis of thoracic duct in zebrafish with or without VEGFR3 Kinase inhibitor pre-impairment. PNS promotes proliferation, migration and tube formation of LECs. The tube formation induced by PNS could be blocked by VEGFR3 Kinase inhibitor. PNS induce VEGF-C expression of LEC, which could be blocked by ERK1/2, PI3K and P38MAPK signaling inhibitors.

Conclusion

PNS activates lymphangiogenesis both in vivo and in vitro by up-regulating VEGF-C expression and activation of ERK1/2, PI3K and P38MAPK signaling. These findings provide a novel insight into the role of PNS in lymphangiogenesis and suggest that it might be an attractive and suitable therapeutic agent for treating secondary lymphedema or other lymphatic system impairment related disease.