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

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Li, Jinlong Chen, Yan Zhang, Li Xing, Lianping Xu, Hao Wang, Yongjun Shi, Qi Liang, Qianqian
Description	Author Affiliation: Li J ( Department of Orthopaedics, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: phjod@163.com.); Chen Y ( Department of Orthopaedics, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: 952026015@qq.com.); Zhang L ( Department of Orthopaedics, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: 15221152917@163.com.); Xing L ( Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, 601 Elmwood Avenue, Rochester, NY 14642, USA); Xu H ( Department of Orthopaedics, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: hoxu@163.com.); Wang Y ( Department of Orthopaedics, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: yjwang8888@126.com.); Shi Q ( Department of Orthopaedics, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: jzyjs200032@126.com.); Liang Q ( Department of Orthopaedics, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: liangqianqiantcm@126.com.)
Abstract	ETHNOPHARMACOLOGICAL RELEVANCE: 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, 100µM) for 48h with or without the 6h pretreatment of the 30µM 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.
File Format	HTM / HTML
ISSN	03788741
Journal	Journal of Ethnopharmacology
Volume Number	193
e-ISSN	18727573
Language	English
Publisher	Elsevier
Publisher Date	2016-12-04
Publisher Place	Ireland
Access Restriction	One Nation One Subscription (ONOS)
Content Type	Text
Resource Type	Article
Subject	Drug Discovery Pharmacology

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