HESPERIDIN MODULATES HYPERTENSION AND THE URINARY METABOLIC PROFILE IN CAFETERIA DIET-FED RATS

Abstract

Introduction: Diet seems to play a crucial role in the development and prevention of cardiovascular disease (CVD). In particular, fruit-rich diets can be an important modifiable factor for reducing CVD-related comorbidities. Hence, orange juice (OJ) consumption has been reported to exert beneficial effects on some CVD risk factors such as blood pressure an endothelial function. Hesperidin represents more than 90% of the flavanones found in OJ but its role on OJ-mediated beneficial effects is far from fully understood. Aim: The principal aim was to evaluate hesperidin`s effect and underline the mechanisms after a chronic consumption in rats fed cafeteria (CAF) diet. Materials and Methods: Eight-week-old male Sprague-Dawley rats (n=40) were fed CAF or standard (STD) diet for 9 weeks. After this, each diet group was supplemented either with vehicle or hesperidin (100 mg/kg) for 8 weeks. Systolic blood pressure (SBP) and body weight were measured every week during treatment. At the end, urine samples were collected and the urinary metabolic profiles were analysed by 1H-NMR spectroscopy. Results: CAF diet significantly increased body weight, fat content, and SBP compared to STD diet. Hesperidin supplementation had no effect on body weight or fat content in either diet group. However, hesperidin treatment reduced SBP in rats fed CAF diet, but did not change it in STD diet-fed rats. In addition, hesperidin supplementation had a significant effect on the urinary metabolic profiles of both diet groups. Thus, it resulted in changes in several gut microbially derived uremic toxins (DMA, PAG, 4-C), and a reduction in the excretion of metabolites related to inflammation and oxidative stress (2-deoxyciditine, allantoin, pseudouridine, NAG, and fucose). Conclusion: Our findings are consistent with the beneficial effect of hesperidin on blood pressure and the urinary metabolic profile, which could be in part related to a change in the microbiota composition and/or functionality after hesperidin supplementation.