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(Reference retrieved automatically from Web of Science through information on FAPESP grant and its corresponding number as mentioned in the publication by the authors.)

p-synephrine induces transcriptional changes via the cAMP/PKA pathway but not cytotoxicity or mutagenicity in human gastrointestinal cells

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Author(s):
Ribeiro, Diego Luis [1] ; Thomazela Machado, Ana Rita [2] ; Machado, Carla [1] ; Aissa, Alexandre Ferro [2] ; Dos Santos, Patrick Wellington [2] ; Mazzaron Barcelos, Gustavo Rafael [3] ; Greggi Antunes, Lusania Maria [2]
Total Authors: 7
Affiliation:
[1] Univ Sao Paulo, Ribeirao Preto Med Sch, Dept Genet, Ribeirao Preto - Brazil
[2] Univ Sao Paulo, Sch Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Ribeirao Preto - Brazil
[3] Univ Fed Sao Paulo, Inst Hlth & Soc, Dept Biosci, BR-11015020 Santos, SP - Brazil
Total Affiliations: 3
Document type: Journal article
Source: JOURNAL OF TOXICOLOGY AND ENVIRONMENTAL HEALTH-PART A-CURRENT ISSUES; v. 84, n. 5 DEC 2020.
Web of Science Citations: 0
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 mu M was not cytotoxic to both cell lines. At 2-200 mu M, 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. (AU)

FAPESP's process: 14/20344-9 - Mutagenicity, genotoxicity and changes in gene expression profile evaluation of synephrine dietary supplement in human cells in vitro
Grantee:Diego Luis Ribeiro
Support type: Scholarships in Brazil - Doctorate