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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 2.3 ) Pub Date : 2020-12-08 , DOI: 10.1080/15287394.2020.1855490
Diego Luis Ribeiro 1 , Ana Rita Thomazela Machado 2 , Carla Machado 1 , Alexandre Ferro Aissa 2 , Patrick Wellington Dos Santos 2 , Gustavo Rafael Mazzaron Barcelos 3 , Lusânia Maria Greggi Antunes 2
Affiliation  

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-辛弗林通过 cAMP/PKA 途径诱导转录变化,但不诱导人胃肠道细胞的细胞毒性或致突变性

摘要

p-辛弗林 (SN) 是一种生物碱,添加到生热制剂中以减轻体重,主要在人体胃肠道 (GI) 中吸收。由于 SN 对 GI 细胞的不利影响尚不清楚,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。- 25–5000 μM 的辛弗林对两种细胞系都没有细胞毒性。在 2-200 μM 时,SN 增加了活性氧 (ROS) 的形成,但也增强了抗氧化防御分子谷胱甘肽 (GSH) 和过氧化氢酶 (CAT) 活性的水平,这可能是两种细胞系均不存在细胞毒性/致突变性的原因. SN 诱导MNP01 细胞中cAMP/PKA 通路基因ADCY3MAPK1和Caco-2 细胞中MAPK1、GNAS、PRKACAPRKAR2A 的表达,并调节与细胞增殖 ( JUN; AKT1 ) 和炎症相关的基因的转录(相对;肿瘤坏死因子) 在两个细胞系中。因此,改善的抗氧化状态减轻了归因于 SN 的促氧化作用。证据表明 SN 似乎没有表现出不利的潜力,但在人 GI 细胞系中调节了 cAMP/PKA 途径。

更新日期:2021-02-09
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