Ferulic acid, a natural polyphenol, alleviates insulin resistance and hypertension in fructose fed rats: Effect on endothelial-dependent relaxation.
Ferulic acid (FER) is a polyphenolic compound contained in various types of fruits. It has a substantial therapeutic effect inhibitory activity against aldose reductase (AR) inhibition. In this study, we examined the effect of FER on fructose-fed rats in comparison to a standard AR inhibitor, zopolrestat (ZOP). We determined the protective role of FER against metabolic syndrome by examining serum insulin/Glucose levels, triglycerides (TGs), cholesterol and advanced glycation end product (AGE) in rats supplied with 10% fructose drinking water. In addition, blood pressure, vascular reactivity of isolated thoracic aortas and acetylcholine-induced NO were all evaluated to estimate the cardiovascular complications of metabolic syndrome (MetS) associated with fructose feeding. Animals were randomly divided into four groups: control, (+10% fructose, Fru), zopolrestat-treated fructose fed (Fru-zop) and ferulic acid-treated fructose fed rats (Fru-Fer). After 12 weeks of FER treatment, we found significant reduction in both hyperinsulinemia and elevated diastolic blood pressure associated with fructose-fed to levels comparable to those achieved with ZOP. Both FER and ZOP significantly augmented the impaired relaxation associated with fructose-fed, whereas neither showed any significant effect on the developed vasoconstriction. Isolated aortas from fructose-fed rats incubated with either FER or ZOP, reinstated normal relaxation response to acetylcholine (ACh). Furthermore, isolated aortas showed attenuated nitric oxide (NO) production following the addition of (ACh), while both FER and ZOP restored normal induction of NO. Taken together, the current study shows that, FER alleviated insulin resistance and hypertension associated with metabolic syndrome compared to the standard AR inhibitor (ZOP). This potential protective effect is at least mediated by restoring endothelial relaxation.
Department of Pharmacology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia; Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt. Electronic address: helbassossy@kau.edu.eg.
Hany
H
El-Bassossy
Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Dina
D
Badawy
Department of Pharmacology, Faculty of Pharmacy, King Abdulaziz University, Jeddah, Saudi Arabia.
Thikryat
T
Neamatallah
Department of Pharmacology, Faculty of Pharmacy, Zagazig University, Zagazig, Egypt.
Ahmed
A
Fahmy
D000109:Acetylcholine / Q000378:metabolism; D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000502:physiology; D052160:Benzothiazoles / Q000494:pharmacology / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects; D003373:Coumaric Acids / Q000494:pharmacology* / Q000627:therapeutic use; D004727:Endothelium / Q000187:drug effects* / Q000502:physiology; D005632:Fructose / Q000633:toxicity; D017127:Glycation End Products, Advanced / Q000032:analysis; D006973:Hypertension / Q000209:etiology / Q000517:prevention & control; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D010793:Phthalazines / Q000494:pharmacology / Q000627:therapeutic use; D059808:Polyphenols / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D014280:Triglycerides / Q000097:blood; D014661:Vasoconstriction / Q000187:drug effects
D052160:Benzothiazoles; D003373:Coumaric Acids; D017127:Glycation End Products, Advanced; D007328:Insulin; D010793:Phthalazines; D059808:Polyphenols; D014280:Triglycerides; C067172:zopolrestat; D005632:Fructose; D009569:Nitric Oxide; C004999:ferulic acid; D000449:Aldehyde Reductase; D000109:Acetylcholine
Aldose reductase; Aorta; Ferulic acid; Metabolic syndrome; Zopolrestat