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

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.

Vitamin D supplementation alters the expression of genes associated with hypertension and did not induce DNA damage in rats.

Vitamin D3 deficiency has been correlated with altered expression of genes associated with increased blood pressure (BP); however, the role of vitamin D3 supplementation in the genetic mechanisms underlying hypertension remains unclear. Thus, the aim of this study was investigate the consequences of vitamin D3 supplemented (10,000 IU/kg) or deficient (0 IU/kg) diets on regulation of expression of genes related to hypertension pathways in heart cells of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) controls. An additional aim was to assess the impact of vitamin D3 on DNA damage and oxidative stress markers. The gene expression profiles were determined by PCR array, DNA damage was assessed by an alkaline comet assay, and oxidative stress markers by measurement of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) levels. In SHR rats data showed that the groups of genes most differentially affected by supplemented and deficient diets were involved in BP regulation and renin-angiotensin system. In normotensive WKY controls, the profile of gene expression was similar between the two diets. SHR rats were more sensitive to changes in gene expression induced by dietary vitamin D3 than normotensive WKY animals. In addition to gene expression profile, vitamin D3 supplemented diet did not markedly affect DNA or levels of TBARS and GSH levels in both experimental groups. Vitamin D3 deficient diet produced lipid peroxidation in SHR rats. The results of this study contribute to a better understanding of the role of vitamin D3 in the genetic mechanisms underlying hypertension. Abbreviations: AIN, American Institute of Nutrition; EDTA, disodium ethylenediaminetetraacetic acid; GSH, glutathione; PBS, phosphate buffer solution; SHR, spontaneously hypertensive rats; TBARS, thiobarbituric acid reactive substances; WKY, Wistar Kyoto.