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Rhamnocitrin extracted from Nervilia fordii inhibited vascular endothelial activation via miR-185/STIM-1/SOCE/NFATc3.

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机构: [1]Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences,National and Local United Engineering Lab of Druggability and New Drugs Evaluation,Guangdong Engineering Laboratoty of Druggability and New Drug Evaluation,Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou, P. R. China [2]Mathematical Engineering Academy of Chinese Medicine,Guangdong Provincial Key Laboratory of New Drug Development and Research of Chinese Medicine, Guangzhou University of Chinese Medicine, Guangzhou, P. R. China [3]Department of obstetrics and gynecology, the first affiliated hospital of Sun Yat-sen University, Guangzhou, P. R. China
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关键词: Rhamnocitrin Endothelial cell inflammation SOCE Calcineurin/NFATc3

摘要:
Vascular endothelial activation is pivotal for the pathological development of various infectious and inflammatory diseases. Therapeutic interventions to prevent endothelial activation are of great clinical significance to achieve anti-inflammatory strategy. Previous studies indicate that the total flavonoids from the endemic herbal medicine Nervilia fordii (Hance) Schltr exerts potent anti-inflammatory effect and protective effect against endotoxin lipopolysaccharide (LPS)-induced acute lung injury, and shows clinical benefit in severe acute respiratory syndromes (SARS). However, the exact effective component of Nervilia fordii and its potential mechanism remain unknown. The aim of this study was to investigate the effect and mechanism of rhamnocitrin (RH), a flavonoid extracted from Nervilia fordii, on LPS-induced endothelial activation. The in vitro endothelial cell activation model was induced by LPS in human umbilical vein endothelial cells (HUVECs). Cell viability was measured to determine the cytotoxicity of RH. RT-PCR, Western blot, fluorescent probe and immunofluorescence were conducted to evaluate the effect and mechanism of RH against endothelial activation. RH was extracted and isolated from Nervilia fordii. RH at the concentration from 10-7 M-10-5 M inhibited the expressions of interlukin-6 (IL-6) and -8 (IL-8), monocyte chemotactic protein-1 (MCP-1), intercellular adhesion molecule-1 (ICAM-1), vascular cell-adhesion molecule-1 (VCAM-1), and plasminogen activator inhibitor-1 (PAI-1) in response to LPS challenge. Mechanistically, RH repressed calcium store-operated Ca2+ entry (SOCE) induced by LPS, which is due to downregulation of stromal interaction molecule-1 (STIM-1) following upregulating microRNA-185 (miR-185). Ultimately, RH abrogated LPS-induced activation of SOCE-mediated calcineurin/NFATc3 (nuclear factor of activated T cells, cytoplasmic 3) signaling pathway. The present study identifies RH as a potent inhibitor of endothelial activation. Since vascular endothelial activation is a pivotal cause of excessive cytokine production, leading to cytokine storm and severe pathology in infectious diseases such as SARS and the ongoing COVID-19 pneumonia disease, RH might suggest promising therapeutic potential in the management of cytokine storm in these diseases. Copyright © 2020 Elsevier GmbH. All rights reserved.

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出版当年[2019]版:
大类 | 2 区 医学
小类 | 1 区 全科医学与补充医学 2 区 药物化学 2 区 药学 2 区 植物科学
最新[2025]版:
大类 | 1 区 医学
小类 | 1 区 药物化学 1 区 全科医学与补充医学 1 区 药学 1 区 植物科学
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出版当年[2018]版:
Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Q1 PHARMACOLOGY & PHARMACY Q1 CHEMISTRY, MEDICINAL Q1 PLANT SCIENCES
最新[2023]版:
Q1 CHEMISTRY, MEDICINAL Q1 INTEGRATIVE & COMPLEMENTARY MEDICINE Q1 PHARMACOLOGY & PHARMACY Q1 PLANT SCIENCES

影响因子: 最新[2023版] 最新五年平均 出版当年[2018版] 出版当年五年平均 出版前一年[2017版] 出版后一年[2019版]

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第一作者机构: [1]Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences,National and Local United Engineering Lab of Druggability and New Drugs Evaluation,Guangdong Engineering Laboratoty of Druggability and New Drug Evaluation,Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou, P. R. China
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通讯机构: [1]Laboratory of Pharmacology and Toxicology, School of Pharmaceutical Sciences,National and Local United Engineering Lab of Druggability and New Drugs Evaluation,Guangdong Engineering Laboratoty of Druggability and New Drug Evaluation,Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Sun Yat-sen University, Guangzhou, P. R. China [*1]Sun Yat-sen University, Guangzhou, China.
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