Current insights and future perspectives of flavonoids: A promising antihypertensive approach

Abstract

Hypertension, or high blood pressure (BP), is a complex disease influenced by various risk factors. It is characterized by persistent elevation of BP levels, typically exceeding 140/90 mmHg. Endothelial dysfunction and reduced nitric oxide (NO) bioavailability play crucial roles in hypertension development. L‐NG‐nitro arginine methyl ester (L‐NAME), an analog of L‐arginine, inhibits endothelial NO synthase (eNOS) enzymes, leading to decreased NO production and increased BP. Animal models exposed to L‐NAME manifest hypertension, making it a useful design for studying the hypertension condition. Natural products have gained interest as alternative approaches for managing hypertension. Flavonoids, abundant in fruits, vegetables, and other plant sources, have potential cardiovascular benefits, including antihypertensive effects. Flavonoids have been extensively studied in cell cultures, animal models, and, to lesser extent, in human trials to evaluate their effectiveness against L‐NAME‐induced hypertension. This comprehensive review summarizes the antihypertensive activity of specific flavonoids, including quercetin, luteolin, rutin, troxerutin, apigenin, and chrysin, in L‐NAME‐induced hypertension models. Flavonoids possess antioxidant properties that mitigate oxidative stress, a major contributor to endothelial dysfunction and hypertension. They enhance endothelial function by promoting NO bioavailability, vasodilation, and the preservation of vascular homeostasis. Flavonoids also modulate vasoactive factors involved in BP regulation, such as angiotensin‐converting enzyme (ACE) and endothelin‐1. Moreover, they exhibit anti‐inflammatory effects, attenuating inflammation‐mediated hypertension. This review provides compelling evidence for the antihypertensive potential of flavonoids against L‐NAME‐induced hypertension. Their multifaceted mechanisms of action suggest their ability to target multiple pathways involved in hypertension development. Nonetheless, the reviewed studies contribute to the evidence supporting the useful of flavonoids for hypertension prevention and treatment. In conclusion, flavonoids represent a promising class of natural compounds for combating hypertension. This comprehensive review serves as a valuable resource summarizing the current knowledge on the antihypertensive effects of specific flavonoids, facilitating further investigation and guiding the development of novel therapeutic strategies for hypertension management.

Associations of Flavonoid Intakes with Mortality among Populations with Hypertension: A Prospective Cohort Study

“…The benefits of flavonoids may be related to their multifaceted bioactivities, including antioxidant [40,41], anti-inflammatory [42,43], anti-platelet aggregation [44,45], modulating gut microbiota [46], and vasodilation [13,47]. Although their bioavailability is limited, this shortcoming is compensated by their potent bioactivities and diverse biological effects.…”

“…Flavonoids can affect arachidonic acid metabolism by inhibiting the expression of cyclooxygenase 2 and lipoxygenase, ultimately exerting the anti-inflammatory effect [42,43]. Finally, flavonoids can also exert antihypertensive effects by increasing the bioavailability of nitric oxide (NO) and modulating vasoactive factors and vasodilation [13,47], and this process may also involve alterations of metabolites associated with gut microbiota [46], such as 3-hydroxyphenylacetic acid [52].…”

“…Flavonoids are naturally occurring polyphenolic compounds that include six subclasses, mainly flavanones, flavones, flavan-3-ols, flavonols, isoflavones, and anthocyanins [11]. Owing to their structural diversity, these subclasses exert different effects, such as antioxidant, anti-inflammatory, immunomodulatory, vasodilation, and antithrombotic [11][12][13]. Growing evidence has affirmed that flavonoids, as well as flavonoid-rich foods (e.g., fruit, vegetables, and tea), were linked not only to a reduced risk of HTN but also to lower all-cause, cancer-related, and CVD-related mortality [14][15][16][17][18][19][20].…”