**1. Introduction**

Cardiovascular diseases (CVDs), including coronary artery disease, atherosclerosis, and hypertension, are a group of diseases that acutely threaten human health [1]. Endothelial dysfunction, a hallmark of hypertension, can be caused by oxidative stress. Nitric oxide (NO) is a crucial mediator of endothelium-dependent relaxation in blood pressure regulation [2]. Increased radicals rapidly react with NO, resulting in altered NO bioavailability and impaired endothelial relaxation [3]. Reactive oxygen species (ROS) affect the structure and function of vascular media. Vascular remodeling by ROS leads to enhanced medial thickness [4]. Therefore, preventing oxidation and ROS generation may help improve hypertension-related diseases [5]. Nuclear factor-E2-related factor 2 (Nrf2), an antioxidant transcription factor important in CVD resistance [6], is highly sensitive to oxidative damage. Nrf2 promotes the transcription of antioxidant genes, including heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase (NQO-1), and glutamate-cysteine ligase catalytic subunit (GCLC). A previous study demonstrated that accumulation of Nrf2 in the nucleus and activation of protein kinase B (Akt) accompanied HO-1 and NQO-1 expression [7]. In the endothelium, many growth factors and hormones act as agonists to induce the activation of Akt and phosphorylation of endothelial nitric oxide synthase (eNOS), which increases NO production [8]. As various endothelial signaling pathways converge on Akt, it may be an ideal target protein for eNOS responses [9]. Therefore, the Akt/eNOS and Nrf2 signaling pathways are crucial checkpoints for the induction of phase II enzymes and treatment of endothelial dysfunction.

Phenolic compounds are the most abundant phytochemicals in plant-based foods. Phenolic acids are a major class of phenolic compounds that can suppress ROS, thus reducing oxidative stress to biomolecules within cells [10]. Phenolic acids exert various biological activities, including antioxidant, anticancer, antidiabetic, anti-inflammatory, and antihypertension [11]. The ameliorative effect of phenolic acids on chronic diseases may

**Citation:** Yu, M.; Kim, H.J.; Heo, H.; Kim, M.; Jeon, Y.; Lee, H.; Lee, J. Comparison of the Antihypertensive Activity of Phenolic Acids. *Molecules* **2022**, *27*, 6185. https://doi.org/ 10.3390/molecules27196185

Academic Editor: Nour Eddine Es-Safi

Received: 31 August 2022 Accepted: 19 September 2022 Published: 21 September 2022

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be due to their high antioxidative potential [12]. Gallic acid suppressed hypertension in L-NAME-treated mice and spontaneously hypertensive rats [13,14]. Ferulic acid reduced oxidative injury by increasing the bioavailability of NO in arterial vasculature [15]. Moreover, chlorogenic acid and caffeic acid lowered blood pressure and decreased the properties of enzymes associated with the pathogenesis of hypertension [16]. However, information on the comparative efficacy of phenolic acids in modulating endothelial dysfunction and hypertension is limited. This study aimed to compare the inhibitory effect of phenolic acids on endothelial dysfunction against the oxidative damages in EA.hy 926 endothelial cells.
