TY - JOUR
T1 - Ferulic acid-4-O-sulfate rather than ferulic acid relaxes arteries and lowers blood pressure in mice
AU - Van Rymenant, Evelien
AU - Van Camp, John
AU - Pauwels, Bart
AU - Boydens, Charlotte
AU - Vanden Daele, Laura
AU - Beerens, Katrijn
AU - Brouckaert, Peter
AU - Smagghe, Guy
AU - Kerimi, Asimina
AU - Williamson, Gary
AU - Grootaert, Charlotte
AU - Van de Voorde, Johan
PY - 2017/6/1
Y1 - 2017/6/1
N2 - Consumption of foods rich in ferulic acid (FA) such as wholegrain cereals, or FA precursors such as chlorogenic acids in coffee, is inversely correlated with risk of cardiovascular disease and type 2 diabetes. As a result of digestion and phase II metabolism in the gut and liver, FA is converted predominantly into ferulic acid-4-O-sulfate (FA-sul), an abundant plasma metabolite. Although FA-sul is the main metabolite, very little has been reported regarding its bioactivities. We have compared the ex vivo vasorelaxing effect of FA and FA-sul (10−7–3.10−5 M) on isolated mouse arteries mounted in tissue myographs. FA-sul, but not FA, elicited a concentration-dependent vasorelaxation of saphenous and femoral arteries and aortae. The FA-sul-mediated vasorelaxation was blunted by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a soluble guanylate cyclase (sGC) inhibitor. The role of sGC was confirmed in femoral arteries isolated from sGCα1(−/−) knockout mice. Furthermore, 4-aminopyridine, a specific inhibitor of voltage-dependent potassium channels, significantly decreased FA-sul-mediated effects. In anesthetized mice, intravenous injection of FA-sul decreased mean arterial pressure, whereas FA had no effect, confirming the results obtained ex vivo. FA-sul is probably one of the major metabolites accounting for the blood pressure-lowering effects associated with FA consumption.
AB - Consumption of foods rich in ferulic acid (FA) such as wholegrain cereals, or FA precursors such as chlorogenic acids in coffee, is inversely correlated with risk of cardiovascular disease and type 2 diabetes. As a result of digestion and phase II metabolism in the gut and liver, FA is converted predominantly into ferulic acid-4-O-sulfate (FA-sul), an abundant plasma metabolite. Although FA-sul is the main metabolite, very little has been reported regarding its bioactivities. We have compared the ex vivo vasorelaxing effect of FA and FA-sul (10−7–3.10−5 M) on isolated mouse arteries mounted in tissue myographs. FA-sul, but not FA, elicited a concentration-dependent vasorelaxation of saphenous and femoral arteries and aortae. The FA-sul-mediated vasorelaxation was blunted by 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one, a soluble guanylate cyclase (sGC) inhibitor. The role of sGC was confirmed in femoral arteries isolated from sGCα1(−/−) knockout mice. Furthermore, 4-aminopyridine, a specific inhibitor of voltage-dependent potassium channels, significantly decreased FA-sul-mediated effects. In anesthetized mice, intravenous injection of FA-sul decreased mean arterial pressure, whereas FA had no effect, confirming the results obtained ex vivo. FA-sul is probably one of the major metabolites accounting for the blood pressure-lowering effects associated with FA consumption.
KW - Blood pressure
KW - Ferulic acid
KW - Ferulic acid-4-O-sulfate
KW - Mouse
KW - Vasorelaxation
KW - Blood pressure
KW - Vasorelaxation
KW - Ferulic acid-4-O-sulfate
KW - Ferulic acid
KW - Ex vivo
U2 - 10.1016/j.jnutbio.2017.02.018
DO - 10.1016/j.jnutbio.2017.02.018
M3 - A1: Web of Science-article
C2 - 28391055
SN - 1873-4847
VL - 44
SP - 44
EP - 51
JO - Journal of Nutritional Biochemistry
JF - Journal of Nutritional Biochemistry
ER -