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Review ARTICLE Provisionally accepted The full-text will be published soon. Notify me

Front. Pharmacol. | doi: 10.3389/fphar.2019.00715

Natural plants compounds as modulators of epithelial-to-mesenchymal transition

  • 1Autonomous University of Zacatecas, Mexico
  • 2Unidad Academica de Medicina Humana y Ciencias de la Salud, Universidad Autónoma de Zacatecas, Mexico
  • 3Severo Ochoa Molecular Biology Center (CSIC-UAM), Spain
  • 4Institute of Health Research of the University Hospital of La Princesa, Spain
  • 5University Hospital La Paz Research Institute (IdiPAZ), Spain

Abstract.
Epithelial to mesenchymal transition (EMT) is a self-regulated physiological process required for tissue repair that in non-controled conditions may lead to fibrosis, angiogenesis, loss of normal organ function or cancer. Although several molecular pathways involved in EMT regulation has been described, this process does not have any specific treatment. This article introduces a systematic review of effective natural plant compounds and their extract that modulates the pathological EMT or its deleterious effects through acting on different cellular signal transduction pathways both in vivo and in vitro. Thereby, cryptotanshinone, resveratrol, oxymatrine, ligustrazine, osthole, codonolactone, betanin, tannic acid, gentiopicroside, curcumin, genistein, paeoniflorin, gambogic acid and cinnamomum cassia extracts, inhibit EMT acting on TGF-β/smads signaling pathway. Gedunin, carnosol, celastrol, black rice anthocyanins, duchesnea indica, cordycepin and celastrus orbiculatus extract downregulate vimectin, fibronectin, and N-cadherin. Sulforaphane, luteolin, celastrol, curcumin, arctigenin inhibit β- catenin signaling pathway. Salvianolic acid-A and plumbagin block oxidative stress, while, honokiol, gallic acid, piperlongumine, brusatol and paeoniflorin inhibit EMT transcription factors such as SNAIL, TWIST and ZEB. Plectranthoic acid, resveratrol, genistein, baicalin, polyphyllin I, cairicoside E, luteolin, berberine, nimbolide, curcumin, withaferin-A, jatrophone, ginsenoside-Rb1, honokiol, parthenolide, phoyunnanin-E, epicatechin-3-gallate, gigantol, eupatolide, baicalin and baicalein and nitidine chloride inhibit EMT acting on other signaling pathways (SIRT1, p38 MAPK, NFAT1, SMAD, IL-6, STAT3, AQP5, notch 1, PI3K/Akt, Wnt/β- catenin, NF-kB, FAK/AKT, Hh). Despite the huge amount of preclinical data regarding EMT modulation by plants natural compounds, clinical translation is poor. Additionally, this review highlights some relevant examples of clinical trials using natural plant compound to modulate EMT and its deleterious effects. In overall, this opens up new therapeutic alternatives in cancer, inflammatory and fibrosing diseases through the control of EMT process.

Keywords: Transición epitelial a mesenquimatosa, Compuestos de plantas naturales., antifibrótico, antiinflamatorio, agente antioxidante

Received: 10 Mar 2019; Accepted: 05 Jun 2019.

Edited by:

Raffaele Strippoli, Sapienza University of Rome, Italy

Reviewed by:

Gautam Sethi, National University of Singapore, Singapore
Marco Cordani, IMDEA Nanociencia, Spain  

Copyright: © 2019 Avila-Carrasco, González, Majano, Sanchez -Tomero, Selgas, López-Cabrera and Aguilera. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

* Correspondence: MD, PhD. Lorena Avila-Carrasco, Autonomous University of Zacatecas, Zacatecas, Mexico, lacdoc_@hotmail.com