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马缨丹(马鞭草科)乙醇提取物诱导人滋养层来源细胞系中 ERK1/2 和 p38MAPKs 通路的激活和 Ca2+失衡。

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

机构信息

Laboratoire de Physiologie Materno-foetale, Département des Sciences Biologiques, Centre de Recherches Biomédicales, Université du Québec à Montréal, Montréal, Québec, Canada.

出版信息

Food Chem Toxicol. 2012 Mar;50(3-4):1001-12. doi: 10.1016/j.fct.2011.12.021. Epub 2011 Dec 24.

DOI:10.1016/j.fct.2011.12.021
PMID:22222932
Abstract

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 μg/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.

摘要

大青(马鞭草科)是一种被用来治疗月经和呼吸道紊乱的药用植物,其叶的乙醇提取物已进行了植物化学和生物学分析。BeWo 和 JEG-3 细胞被用于评估人绒毛膜促性腺激素(hCG)的产生、合胞体的形成、Ca2+摄取和 Ca2+处理蛋白的表达。还研究了 cAMP 的产生和丝裂原活化蛋白激酶(MAPKs)的磷酸化。植物化学分析产生了三种三萜:齐墩果酸、熊果酸和拉坦酸。细胞活力测定显示无明显的细胞毒性作用。观察到 hCG 的产生显著减少,但 BeWo 细胞融合没有受到干扰。单独的大青提取物对 cAMP 途径没有影响;尽管 forskolin 诱导的 cAMP 产生减少。ERK1/2 和 p38 MAPKs 通路均被激活。24 小时处理后观察到细胞内 Ca2+浓度([Ca2+]i)呈时间和剂量依赖性增加;然而,只有大青在 10μg/mL 时,在 10 分钟处理后才会引起 [Ca2+]i 的增加。CaBP28K 和 PMCA1/4 在蛋白和 mRNA 水平上分别被调节。这项研究首次显示了大青叶中的三萜类化合物对滋养层样细胞的影响,并表明这种植物在胎盘发育和胎儿生长方面可能具有潜在的毒性作用。

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