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

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

  • Phytomedicine. 2020 Dec:79:153350. doi: 10.1016/j.phymed.2020.153350.
Tong Lin 1,  Wenwei Luo 1,  Ziqing Li 1,  Lili Zhang 1,  Xinghan Zheng 2,  Liting Mai 2,  Wanqi Yang 1,  Guimei Guan 3,  Ziren Su 2,  Peiqing Liu 1,  Zhuoming Li 4,  Youliang Xie 5
Affiliations

Affiliations

  • 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.
  • 4 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. Electronic address: lizhm5@mail.sysu.edu.cn.
  • 5 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. Electronic address: xieyl@gzucm.edu.cn.
PMID: 33002827 DOI: 10.1016/j.phymed.2020.153350
Abstract

Background: 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.

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords

Calcineurin/NFATc3; Endothelial cell inflammation; Rhamnocitrin; SOCE.

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