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p-synephrine induces transcriptional changes via the cAMP/PKA pathway but not cytotoxicity or mutagenicity in human gastrointestinal cells
Journal of Toxicology and Environmental Health, Part A ( IF 2.6 ) Pub Date : 2020-12-08
Diego Luis Ribeiro, Ana Rita Thomazela Machado, Carla Machado, Alexandre Ferro Aissa, Patrick Wellington Dos Santos, Gustavo Rafael Mazzaron Barcelos, Lusânia Maria Greggi Antunes

ABSTRACT

p-Synephrine (SN) is an alkaloid added to thermogenic formulations for weight loss that is predominantly absorbed in the human gastrointestinal tract (GI). As the adverse effects of SN on GI cells remain unclear, the aim of present study was to examine whether SN affected cell viability, cell cycle kinetics, genomic stability, redox status, and expression of cAMP/PKA pathway genes related to metabolism/energy homeostasis in stomach mucosa (MNP01) and colon adenocarcinoma (Caco-2) human cells. p-Synephrine at 25–5000 μM was not cytotoxic to both cell lines. At 2–200 μM, SN increased the formation of reactive oxygen species (ROS) but also enhanced levels of antioxidant defense molecules glutathione (GSH) and catalase (CAT) activity, which may account for the absence of cytotoxicity/mutagenicity in both cell lines. SN induced expression of the cAMP/PKA pathway genes ADCY3 and MAPK1 in MNP01 cells and MAPK1, GNAS, PRKACA, and PRKAR2A in Caco-2 cells, as well as modulated the transcription of genes related to cell proliferation (JUN; AKT1) and inflammation (RELA; TNF) in both cell lines. Therefore, the improved antioxidant state mitigated pro-oxidative effects attributed to SN. Evidence indicates that SN does not appear to exhibit adverse potential but modulated the cAMP/PKA pathway in human GI cell lines.



中文翻译:

p-synephrine通过cAMP / PKA途径诱导转录变化,但对人胃肠道细胞无细胞毒性或致突变性

摘要

p- Synephrine(SN)是一种添加到产热配方中以减轻体重的生物碱,该生物碱主要在人体胃肠道(GI)中吸收。由于尚不清楚SN对GI细胞的不良影响,本研究的目的是检查SN是否影响细胞活力,细胞周期动力学,基因组稳定性,氧化还原状态以及与代谢/能量稳态相关的cAMP / PKA通路基因的表达。在胃粘膜(MNP01)和结肠腺癌(Caco-2)人类细胞中的表达。p-25–5000μM的Synephrine对两种细胞系均无细胞毒性。在2–200μM时,SN增加了活性氧(ROS)的形成,但同时也提高了抗氧化剂防御分子谷胱甘肽(GSH)和过氧化氢酶(CAT)的活性,这可能解释了两种细胞系均不具有细胞毒性/致突变性。SN诱导cAMP / PKA通路基因ADCY3MAPK1在MNP01细胞中表达以及MAPK1,GNAS,PRKACAPRKAR2A在Caco-2细胞中表达,并调节与细胞增殖(JUN; AKT1)相关的基因的转录(RELA; TNF)在两个单元格中。因此,改善的抗氧化剂状态减轻了归因于SN的促氧化作用。有证据表明,SN在人的GI细胞系中似乎没有表现出不利的电位,但调节了cAMP / PKA途径。

更新日期:2020-12-09
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