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 have 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 transforming growth factor-β (TGF-β)/Smads signaling pathways. 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 pathways. 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-κB, FAK/AKT, Hh). Despite the huge amount of preclinical data regarding EMT modulation by the natural compounds of plant, clinical translation is poor. Additionally, this review highlights some relevant examples of clinical trials using natural plant compounds to modulate EMT and its deleterious effects. Overall, this opens up new therapeutic alternatives in cancer, inflammatory and fibrosing diseases through the control of EMT process.
Highlights
Epithelial-to-mesenchymal transition (EMT) is a tightly regulated physiological process implicated in tissue repair and in embryogenesis (Thiery et al, 2009)
Likewise, suggested that paeonol inactivated extracellular signal-regulated kinase (ERK) and transforming growth factor (TGF)-beta1/Smad pathway leading to regulation of relevant EMT markers. These results suggest that paeonol might be developed as a potential agent used for oxidative stress injury and EMT in premalignant lesion (Yang et al, 2018)
A key target of the effects of Natural plant compounds (NPCs) may be in suppressing oxidative stress and the induction of 5′AMP-activated Kinase (AMPK), or suppression of the WNT/beta-catenin, PI3K/Akt/mammalian target of rapamycin (mTOR) and RAS/MEK/ERK signaling pathways, among others, which results in cell death or prevents aging, diabetes, cardiovascular, cancer and other diseases (McCubrey et al, 2017)
Summary
Epithelial-to-mesenchymal transition (EMT) is a tightly regulated physiological process implicated in tissue repair and in embryogenesis (Thiery et al, 2009). Group 19 acts by down-regulating N-cadherin expression: Tannic acid, Paeoniflorin, Gedunin, Celastrus orbiculatus extract, Celastrol Duchesnea indica, Cordycepin, Nitidine chloride, Honokiol, Phoyunnanin E, Gigantol, Gallic acid, Berberine and Nimbolide. Group 20 acts by downregulating Vimentin expression: α-solanine Tannic acid, Cinnamomum cassia extracts, Paeoniflorin, Withaferin A, Jatrophone, Gedunin, Celastrus orbiculatus extract, Celastrol Black rice anthocyanins, Duchesnea indica, Nitidine chloride, Plumbagin, Phoyunnanin E, Gigantol, Gallic acid, Berberine and Nimbolide. In human lung cancer cells, ARC has been shown to inhibit TGF-β-induced phosphorylation, smad2/3 transcriptional activity, snail and N-cadherin expression, by contrast increasing the expression of E-cadherin in dose and time dependent manners. It blocks ERK-phosphorylation and β-catenin transcriptional activity. Controls the TNF-α/TGF-β-induced EMT and modulating the activation of miR-200c
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