The Antioxidative Effects of Flavones in Hypertensive Disease

Abstract

Hypertension is the leading remediable risk factor for cardiovascular morbidity and mortality in the United States. Excess dietary salt consumption, which is a catalyst of hypertension, initiates an inflammatory cascade via activation of antigen-presenting cells (APCs). This pro-inflammatory response is driven primarily by sodium ions (Na⁺) transporting into APCs by the epithelial sodium channel (ENaC) and subsequent NADPH oxidase activation, leading to high levels of oxidative stress. Oxidative stress, a well-known catalyst for hypertension-related illness development, disturbs redox homeostasis, which ultimately promotes lipid peroxidation, isolevuglandin production and an inflammatory response. Natural medicinal compounds derived from organic materials that are characterized by their anti-inflammatory, anti-oxidative, and anti-mutagenic properties have recently gained traction amongst the pharmacology community due to their therapeutic effects. Flavonoids, a natural phenolic compound, have these therapeutic benefits and can potentially serve as anti-hypertensives. Flavones are a type of flavonoid that have increased anti-inflammatory effects that may allow them to act as therapeutic agents for hypertension, including diosmetin, which is able to induce significant arterial vasodilation in several different animal models. This review will focus on the activity of flavones to illuminate potential preventative and potential therapeutic mechanisms against hypertension.

Keywords: NADPH oxidase; diosmetin; flavone; flavonoid; hypertension; inflammation; molecular pharmacology; protein kinase C (PKC).

Figure 1

Salt-sensitive hypertension pathway.

Figure 2

Flavonoid carbon numbers and ring names. (A) benzene ring; (B) phenyl ring; (C) heterocyclic ring.

Figure 3

Types of flavonoids.

Figure 4

Structure of diosmetin.

Figure 5

Illustration of Smad3 phosphorylation inhibition by flavones through the inhibition of LSD1A and the JAK2/STAT3 pathway.

Figure 6

Illustration of flavones inhibiting increased intracellular calcium ion concentration through inhibition of PKC-mediated phosphorylation of p47phox.

Figure 7

Flavonoids play a role in scavenging ROS through the activation of the Nrf2/HO-1 pathway and potentially direct intracellular ROS scavenging.

Figure 8

Flavones inhibit hypertension associated inflammation by inhibiting AhR and CYP1A1.

Figure 9

MRP-1 stops the intracellular anti-inflammatory response through inhibition of GSH-mediated ROS and lipid peroxide scavenging; inhibition of MRP-1 by diosmetin supports this intracellular anti-inflammatory response.

Figure 10

Flavone activity in different hypertensive pathways and potential hypertension-inhibiting mechanisms.