Lantana macrophylla Schauer (Verbenaceae) ethanolic extract induces activation of ERK1/2 and p38 MAPKs pathway and Ca²⁺ imbalance in human trophoblasts derived cell lines

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• 作者：Aline O. da Concei&#231 ; &#227 ; o^a ; ^b ; Fernando F. de Oliveira^e ; Rosilene A. de Oliveira^e ; Ademir de J. da S. Junior^e ; Larissa Takser^d ; Carlos Reyes-Moreno^f ; Julie Lafond^a ; ^b ; ^c ; ^{lafond.julie@uqam.ca}
• 关键词：1 ; 25-(OH)2D3 ; vitamin D3 ; cAMP ; cyclic adenosine monophosphate ; BSA ; bovine serum albumin ; [Ca2+]i ; intracellular Ca2+ concentration ; CaBP28K ; calcium binding protein 28K ; DMSO ; dimethyl sulfoxide ; ECL ; enhanced chemiluminescence ; EGTA ; ethylene glycol te
• 刊名：Food and Chemical Toxicology
• 出版年：2012
• 期刊代码：20_02786915
• 类别：pha
• 出版时间：March-April, 2012
• 卷：50
• 期：3-4
• 页码：1001-1012
• 文件大小：1454 K

摘要

Lantana macrophylla Schauer (Verbenaceae) a medicinal plant used to treat menstrual and respiratory disorders was investigated. The ethanolic extract from leaves was subjected to phytochemical and biological analysis. BeWo and JEG-3 cells were used to evaluate human chorionic gonadotropin hormone (hCG) production, syncytial formation, Ca²⁺ uptake and Ca²⁺ handling protein expression. The cAMP production and the mitogen-activated protein kinases (MAPKs) phosphorylation were also investigated. Phytochemical analysis yield three triterpenes: oleanolic, ursolic and latonolic acid. Viability assay showed no significant cytotoxic effect. A significant decrease in hCG production but not a disturbance on BeWo cell fusion were observed. The cAMP pathway was not affected by L. macrophylla extract alone; although the cAMP production inducted by forskolin was diminished. Both ERK1/2 and p38 MAPKs pathways were activated. Increased intracellular Ca²⁺ concentration ([Ca²⁺]i) was observed after 24 h treatment in a time and dose dependent manner; however only L. macrophylla at 10 渭g/mL induced increased [Ca²⁺]i after 10 min treatment. CaBP28K and PMCA1/4 were modulated at protein and mRNA levels, respectively. This study showed for the first time the effect of triterpenoids from L. macrophylla leaves on trophoblasts-like cells and indicates a potential toxic effect of this plant in the placental development and fetal growth.