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Pro-angiogenic Activity of notoginsenoside r1 in Human Umbilical Vein Endothelial Cells in vitro and in a Chemical-Induced Blood Vessel Loss Model of Zebrafish in vivo

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Chinese Journal of Integrative Medicine 2016年第6期22卷 420-429页

作者：杨彬睿洪思佳李铭源丛伟红万建波张哲睿张庆文张燚王一涛林志秀 State Key Laboratory of Quality research in Chinese Medicine Institute of Chinese Medical SciencesUniversity of Macao School of Chinese Medicine The Chinese University of Hong Kong Laboratory of Cardiovascular Diseases Xiyuan Hospital China Heart Institute of Chinese Medicine China Academy of Chinese Medical Sciences

Objective： This study aimed at investigating whether notoginsenoside r1 （r1）, a unique saponin found in Panax notoginseng could promote angiogenic activity on human umbilical vein endothelial cells （HUVECs） and elucidate their potential molecular mechanisms. In addition, vascular restorative activities of r1 was assessed in a chemically-induced blood vessel loss model in zebrafish. Methods： The in vitro angiogenic effect of r1 was compared with other previously reported angiogenic saponins rgl and re. The HUVECs proliferation in the presence of r1 was determined by cell proliferation kit lI （XTI＇） assay. r1, rgl and re-induced HUVECs invasion across polycarbonate membrane was stained with Hoechst-33342 and quantified microscopically. Tube formation assay using matrigel- coated wells was performed to evaluate the pro-angiogenic actions of rI. In order to understand the mechanism underlying the pro-angiogenic effect, various pathway inhibitors such as SU5416, wortmannin （wort） or L-N （o -nitro- L-arginine methyl ester hydrochloride （L-NAME）, SH-6 were used to probe the possible involvement of signaling pathway in the r1 mediated HUVECs proliferation. In in vivo assays, zebrafish embryos at 21 hpf were pre-treated with vascular endothelial growth factor （VEGF） receptor kinase inhibitor ]1 （VrI） for 3 h only and subsequently post-treated with r1 for 48 h, respectively. The intersegmental vessels （ISVs） in zebrafish were assessed for the restorative effect of r1 on defective blood vessels. results： r1 could stimulate the proliferation of HUVECs. In the chemoinvasion assay, r1 significantly increased the number of cross-membrane HUVECs. In addition, r1 markedly enhanced the tube formation ability of HUVECs. The proliferative effects of these saponins on HUVECs were effectively blocked by the addition of SU5416 （a VEGF-KDr/FIk-1 inhibitor）. Similarly, pre-treatment with wort [a phosphatidylinositol 3-kinase （PI3K）-kinase inhibitor], L-NAME [an endothelial nitric oxide synt

关键词： notoginsenoside r1 ginsenoside rgl,ginsenoside re human umbilical vein endothelial cell,zebrafish angiogenesis

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Effect of notoginsenoside r1 on hepatic microcirculation disturbance induced by gut ischemia and reperfusion

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World Journal of Gastroenterology 2008年第1期14卷 29-37页

作者： Wei-Xing Chen Fang Wang, Yu-Ying Liu, Qing-Jiang Zeng, Kai Sun, Xin Xue, Xiang Li, Ji-Ying Yang, Li-Hua An,Bai-He Hu, Jin-Hui Yang, Chuan-She Wang, Zhi-Xin Li, Lian-Yi Liu, Yan Li, Jun Zheng, Fu-Long Liao, Dong Han,Jing-Yu Fan, Jing-Yan Han Fang Wang Yu-Ying Liu Qing-Jiang Zeng Kai Sun Xin Xue Xiang Li Ji-Ying Yang Li-Hua An Bai-He Hu Jin-Hui Yang Chuan-She Wang Zhi-Xin Li Lian-Yi Liu Yan Li Jun Zheng Fu-Long Liao Dong Han Jing-Yu Fan Jing-Yan Han Tasly Microcirculation research Center Peking University Health Science Center Beijing 100083 China Department of Pharmacology Tianjin University of Traditional Chinese Medicine Tianjin 300193 China Department of Integrated Chinese and Western Medicine School of Basic Medical Sciences Peking University Beijing 100083 China

AIM： To assess the effect of notoginsenoside r1 on hepatic microcirculatory disturbance induced by gut ischemia/reperfusion （I/r） in mice. METHODS： The superior mesenteric artery （SMA） of C57/BL mice was ligated for 15 min to induce gut ischemia followed by 30-rain reperfusion. In another set of experiments, r1 was continuously infused （10 mg/kg per hour） from 10 min before I/r until the end of the investigation to study the influence of r1 on hepatic microcirculatory disturbance induced by gut I/r. Hepatic microcirculation was observed by inverted microscopy, and the vascular diameter, red blood cell （rBC） velocity and sinusoid perfusion were estimated. Leukocyte rolling and adhesion were observed under a laser confocal microscope. Thirty and 60 min after reperfusion, lactate dehydrogenase （LDH）, alanine aminotransferase （ALl＇） and aspartate transaminase （AST） in peripheral blood were determined. The expression of adhesion molecules CD11b/CD18 in neutrophils and tumor necrosis factor- alpha （TNF-α）, interleukin-6 （IL-6） and monocyte chemotactic protein-1 （MCP-1） in plasma were evaluated by flow Oltometry. E-selectin and intercellular adhesion molecule-1 （ICAM-1） in hepatic tissue were examined by ***： After gut I/r, the diameters of terminal portal venules and central veins, rBC velocity and the number of perfused sinusoids were decreased, while the leukocyte rolling and adhesion, the expression of E-selectin in hepatic vessels and CD18 in neutrophils, IL-6, MCP-1, LDH, ALT and AST were increased. r1 treatment attenuated these alterations except for IL-6 and MCP-1. CONCLUSION： r1 prevents I/r-induced hepatic microcirculation disturbance and hepatocyte injury, The effect of r1 is related to its inhibition of leukocyte rolling and adhesion by inhibiting the expression of E-selectin in endothelium and CD18 in neutrophils.

关键词： Ischemia/reperfusion notoginsenoside r1 Leukoytes adhesion E-selectin Hepatic injury

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Pharmacological properties and mechanisms of notoginsenoside r1 in ischemia-reperfusion injury

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Chinese Journal of Traumatology 2023年第1期26卷 20-26页

作者： Ting Zhu Qi Wan Institute of Neuroregeneration&Neurorehabilitation Department of PathophysiologySchool of Basic MedicineQingdao UniversityQingdao266071Shandong ProvinceChina

Panax notoginseng is an ancient Chinese medicinal plant that has great clinical value in regulating cardiovascular disease in *** a single component of panax notoginosides,notoginsenoside r1(NGr1)belongs to the panaxatriol *** reports have demonstrated that NGr1 exerts multiple pharmacological effects in ischemic stroke,myocardial infarction,acute renal injury,and intestinal ***,we outline the available reports on the pharmacological effects of NGr1 in ischemia-reperfusion(I/r)*** also discuss the chemistry,composition and molecular mechanism underlying the anti-I/r injury effects of ***1 had significant effects on reducing cerebral infarct size and neurological deficits in cerebral I/r injury,ameliorating the impaired mitochondrial morphology in myocardial I/r injury,decreasing kidney injury molecule-1 and neutrophil gelatinase-associated lipocalin in renal I/r injury and attenuating jejunal mucosal epithelium injury in intestinal I/r *** various organ anti-I/r injury effects of NGr1 are mainly through the suppression of oxidative stress,apoptosis,inflammation,endoplasmic reticulum stress and promotion of angiogenesis and *** findings provide a reference basis for future research of NGr1 on I/r injury.

关键词： notoginsenoside r1 Ischemia/reperfusion injury Chemistry Pharmacological properties Molecular mechanism

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Thin Layer Identification of Jiedu Shengxue Granules and Determination of notoginsenoside r1 Content

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Medicinal Plant 2024年第1期15卷 71-74页

作者： Zhenying FU Bing QING Yinghong HUANG Xianyi SHI Meiyan QIU Xian PENG Jiangcun WEI Fengzhen LI Wen ZHONG Guangxi International Zhuang Medical Hospital Nanning 530201China

[Objectives]To establish the quality standard of hospital preparation Jiedu Shengxue granules.[Methods]Scleromitrion diffusum and Prunella vulgaris in Jiedu Shengxue granules were qualitatively identified by thin layer chromatography(TLC).A high performance liquid chromatography(HPLC)was established to determine the content of notoginsenoside r1 in the granule.[results]The traditional Chinese medicinal materials in Jiedu Shengxue granules could be identified by TLC,and the characteristic spots were stable and *** r1 had a good linear relationship in the range of 10.45-104.5μg/mL,with an average recovery of 98.52%and rSD=2.36%.[Conclusions]TLC and HPLC,as the quality control methods of Jiedu Shengxue granules,have high accuracy and good repeatability,which lays a foundation for the quality control of this mixture.

关键词： Jiedu Shengxue granules Thin layer identification notoginsenoside r1 Quality standard

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