Flavonoids as Natural Anti-Inflammatory Agents Targeting Nuclear Factor-Kappa B (NFκB) Signaling in Cardiovascular Diseases: A Mini Review

Flavonoids are a group of phytochemicals that have shown numerous health effects and have therefore been studied extensively. Of the six common food flavonoid classes, flavonols are distributed ubiquitously among different plant foods whereas appreciable amounts of isoflavones are found in leguminous plant-based foods. Flavonoids have shown promising health promoting effects in human cell culture, experimental animal and human clinical studies. They have shown antioxidant, hypocholesterolemic, anti-inflammatory effects as well as ability to modulate cell signaling and gene expression related disease development. Low bioavailability of flavonoids has been a concern as it can limit or even hinder their health effects. Therefore, attempts to improve their bioavailability in order to improve the efficacy of flavonoids are being studied. Further investigations on bioavailability are warranted as it is a determining factor for flavonoid biological activity.

The intake of flavonols, flavones and isoflavones by Japanese women was calculated from our food-phytochemical composition table. The relationship between intake of these phytochemicals and various anthropometric and blood chemistry data was analyzed in a cross-sectional study. The subjects were 115 women volunteers, aged 29-78 y, living in the northern part of Japan. Each subject completed a 3-d dietary record and received a health check up, including urine and blood sampling for biochemical analysis. Total mean intakes of flavonoids (sum of flavonols and flavones) and isoflavones were 16.7 and 47.2 mg/d, respectively. The major source of flavonoids was onions (45.9%) and that of isoflavones was tofu (37.0%). Total intake of isoflavones exceeded that of other dietary antioxidants, such as flavonoids, carotenoids (3.5 mg/d) and vitamin E (8.2 mg/d), and was approximately one half of the vitamin C intake (109 mg/d). The total intake of flavonoids was inversely correlated with the plasma total cholesterol concentration (TC) (r = -0.236, P: < 0.05) and plasma LDL cholesterol concentration (LDL-C) (r = -0.220, P: < 0.05), after the adjustment for age, body mass index and total energy intake. As a single component, quercetin was inversely correlated with both TC (r = -0.261, P: < 0.01) and LDL-C (r = -0. 263, P: < 0.01). Among Japanese, flavonoid and isoflavone intake is the main component among nonnutrient phytochemicals with antioxidant potential in the diet. These results suggest that a high consumption of both flavonoids and isoflavones by Japanese women may contribute to their low incidence of coronary heart disease compared with women in other countries.

Cardiovascular disease is the leading cause of death worldwide. Despite advancements in diagnosis and treatment of cardiovascular disease, the incidence of cardiovascular disease is still rising. Therefore, new lines of medications are needed to treat the growing population of patients with cardiovascular disease. Although the majority of the existing pharmacotherapies for cardiovascular disease are synthesized molecules, natural compounds, such as resveratrol, are also being tested. Resveratrol is a non-flavonoid polyphenolic compound, which has several biological effects. Preclinical studies have provided convincing evidence that resveratrol has beneficial effects in animal models of hypertension, atherosclerosis, stroke, ischemic heart disease, arrhythmia, chemotherapy-induced cardiotoxicity, diabetic cardiomyopathy, and heart failure. Although not fully delineated, some of the beneficial cardiovascular effects of resveratrol are mediated through activation of silent information regulator 1 (SIRT1), AMP-activated protein kinase (AMPK), and endogenous anti-oxidant enzymes. In addition to these pathways, the anti-inflammatory, anti-platelet, insulin-sensitizing, and lipid-lowering properties of resveratrol contribute to its beneficial cardiovascular effects. Despite the promise of resveratrol as a treatment for numerous cardiovascular diseases, the clinical studies for resveratrol are still limited. In addition, several conflicting results from trials have been reported, which demonstrates the challenges that face the translation of the exciting preclinical findings to humans. Herein, we will review much of the preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular disease and provide information about the physiological and molecular signaling mechanisms involved. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes.