This product is isolated and purified from the herbs of Piper longum
4-Hydroxy MethylesterCinnaMatc/METHYL 4-COUMARATE/4-hydroxycinnamic acid methyl ester/Methyl trans-p-Coumarate/METHYL P-HYDROXYCINNAMATE/Methyl (2Z)-3-(4-hydroxyphenyl)acrylate/Methyl trans-4-Hydroxycinnamate/Methyl 4-hydroxyphenylacrylate/METHYL COUMARATE/METHYL 3-HYDROXYCINNAMATE/trans-4-Hydroxycinnamic Acid Methyl Ester/(E)-Methyl 3-(4-hydroxyphenyl)acrylate/4-hydroxyphenyl-acrylic acid methyl ester/2-Propenoic acid, 3-(4-hydroxyphenyl)-, methyl ester, (2Z)-/Methyl trans-p-hydroxycinnaMate/trans-p-Coumaric Acid Methyl Ester
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Para-coumaric acid methyl ester (pCAME) is one of the bioactive components of Costus speciosus (Koen) Sm. (Zingiberaceae). This plant is traditionally used in Asia to treat catarrhal fevers, worms, dyspepsia, and skin diseases.
To investigate the anti-angiogenic activity of pCAME and its molecular mechanism of action.
We investigated the anti-angiogenic activity of pCAME on human umbilical vein endothelial cells (HUVECs) in vitro and zebrafish (Danio rerio) in vivo.
In vitro cell proliferation, would healing, migration and tube formation assays were used, along with in vivo physiological angiogenic vessel formation, tumor-induced angiogenic vessel formation assays on zebrafish model. qRT-PCR and RNA-seq were also used for the target investigation.
pCAME could inhibit the proliferation, would healing, migration and tube formation of HUVECs, disrupt the physiological formation of intersegmental vessels (ISVs) and the subintestinal vessels (SIVs) of zebrafish embryos, and inhibit tumor angiogenesis in the zebrafish cell-line derived xenograft (zCDX) model of SGC-7901 in a dose-dependent manner. Mechanistic studies revealed that pCAME inhibited vegf/vegfr2 and ang/tie signaling pathways in zebrafish by quantitative RT-PCR analysis, and regulated multi-signaling pathways involving immune, inflammation and angiogenesis in SGC-7901 zCDX model by RNA-seq analysis.
pCAME may be a multi-target anti-angiogenic drug candidate and hold great potential for developing novel therapeutic strategy for cancer treatment.
Copyright © 2018 Elsevier GmbH. All rights reserved.
Anti-angiogenic activity; HUVEC; Xenograft; Zebrafish; pCAME
Anti-angiogenic activity of para-coumaric acid methyl ester on HUVECs in vitro and zebrafish in vivo.
Zhang HZ1, Li CY1, Wu JQ1, Wang RX2, Wei P1, Liu MH3, He MF4.
2018 Sep 15
Pathological increases in adipogenic potential with decreases in osteogenic differentiation occur in osteoporotic bone marrow cells. Previous studies have shown that bioactive materials isolated from natural products can reciprocally regulate adipogenic and osteogenic fates of bone marrow cells. In this study, we showed that Eupatorium japonicum stem extracts (EJE) suppressed lipid accumulation and inhibited the expression of adipocyte markers in multipotent C3H10T1/2 and primary bone marrow cells. Conversely, EJE stimulated alkaline phosphatase activity and induced the expression of osteoblast markers in C3H10T1/2 and primary bone marrow cells. Daily oral administration of 50 mg/kg of EJE for 6 weeks to ovariectomized rats prevented body weight increase and bone mineral density decrease. Finally, activity-guided fractionation led to the identification of coumaric acid and coumaric acid methyl ester as bioactive anti-adipogenic and pro-osteogenic components in EJE. Taken together, our data indicate a promising possibility of E. japonicum as a functional food and as a therapeutic intervention for preventing osteoporosis and bone fractures.
C3H10T1/2; Eupatorium japonicum; bone marrow; coumaric acid; osteoporosis; ovariectomized rat
Reciprocal regulation of adipocyte and osteoblast differentiation of mesenchymal stem cells by Eupatorium japonicum prevents bone loss and adiposity increase in osteoporotic rats.
Kim MJ1, Jang WS, Lee IK, Kim JK, Seong KS, Seo CR, Song NJ, Bang MH, Lee YM, Kim HR, Park KM, Park KW.
Zebrafish have recently emerged as an attractive model for the in vivo bioassay-guided isolation and characterization of pharmacologically active small molecules of natural origin. We carried out a zebrafish-based phenotypic screen of over 3000 plant-derived secondary metabolite extracts with the goal of identifying novel small-molecule modulators of the BMP and Wnt signaling pathways. One of the bioactive plant extracts identified in this screen – Jasminum gilgianum, an Oleaceae species native to Papua New Guinea – induced ectopic tails during zebrafish embryonic development. As ectopic tail formation occurs when BMP or non-canonical Wnt signaling is inhibited during the tail protrusion process, we suspected a constituent of this extract to act as a modulator of these pathways. A bioassay-guided isolation was carried out on the basis of this zebrafish phenotype, identifying para-coumaric acid methyl ester (pCAME) as the active compound. We then performed an in-depth phenotypic analysis of pCAME-treated zebrafish embryos, including a tissue-specific marker analysis of the secondary tails. We found pCAME to synergize with the BMP-inhibitors dorsomorphin and LDN-193189 in inducing ectopic tails, and causing convergence-extension defects in compound-treated embryos. These results indicate that pCAME may interfere with non-canonical Wnt signaling. Inhibition of Jnk, a downstream target of Wnt/PCP signaling (via morpholino antisense knockdown and pharmacological inhibition with the kinase inhibitor SP600125) phenocopied pCAME-treated embryos. However, immunoblotting experiments revealed pCAME to not directly inhibit Jnk-mediated phosphorylation of c-Jun, suggesting additional targets of SP600125, and/or other pathways, as possibly being involved in the ectopic tail formation activity of pCAME. Further investigation of pCAME’s mechanism of action will help determine this compound’s pharmacological utility.
A phenotypic screen in zebrafish identifies a novel small-molecule inducer of ectopic tail formation suggestive of alterations in non-canonical Wnt/PCP signaling.
Gebruers E1, Cordero-Maldonado ML2, Gray AI3, Clements C3, Harvey AL3, Edrada-Ebel R3, de Witte PA1, Crawford AD4, Esguerra CV1.
2013 Dec 11