Twelve-Week Protocatechuic Acid Administration Improves Insulin-Induced and Insulin-Like Growth Factor-1-Induced Vasorelaxation and Antioxidant Activities in Aging Spontaneously Hypertensive Rats

Abstract

Protocatechuic acid (PCA), a strong antioxidant, has been reported for its cardiovascular-protective effects. This study aimed to investigate the effects of PCA administration on vascular endothelial function, mediated by insulin and insulin-like growth factor-1 (IGF-1), and antioxidant activities in aging hypertension. Thirty-six-week-old male aging spontaneously hypertensive rats were randomly divided into vehicle control (SHR) and PCA (SHR+PCA) groups, while age-matched Wistar–Kyoto rats (WKY) served as the normotensive vehicle control group. The oral PCA (200 mg/kg/day) was administered daily for a total of 12 weeks. When the rats reached the age of 48 weeks, the rat aortas were isolated for the evaluation of vascular reactivity and Western blotting. Also, nitric oxide (NO) production and antioxidant activities were examined among the three groups. The results showed that, when compared with the SHR group, the insulin-induced and IGF-1-induced vasorelaxation were significantly improved in the SHR+PCA group. There was no significant difference in the endothelium-denuded vessels among the three groups. After the pre-incubation of phosphatidylinositol 3-kinase (PI3K) or NO synthase (NOS) inhibitors, the vasorelaxation was abolished and comparable among the three groups. The protein levels of insulin receptors, IGF-1 receptors, phospho-protein kinase B (p-Akt)/Akt, and phospho-endothelial NOS (p-eNOS)/eNOS in aortic tissues were significantly enhanced in the SHR+PCA group when compared with the SHR group. Moreover, significant improvements of nitrate/nitrite concentration and antioxidant activities, including superoxide dismutase, catalase, and total antioxidants, were also found in the SHR+PCA group. In conclusion, the 12 weeks of PCA administration remarkably improved the endothelium-dependent vasorelaxation induced by insulin and IGF-1 in aging hypertension through enhancing the PI3K–NOS–NO pathway. Furthermore, the enhanced antioxidant activities partly contributed to the improved vasorelaxation.

Antioxidant Effects and Cytoprotective Potentials of Herbal Tea against H2O2-Induced Oxidative Damage by Activating Heme Oxygenase1 Pathway

“…Phenolic compounds are polyhydroxylated compounds, constituting one of the most extensive groups of naturally active chemicals and exhibiting a variety of biological functions such as protection against oxidative stress-induced diseases [ 22 ]. In this study, we identified six phenolic acids from WHT, and they all exhibited high antioxidant activity, which is consistent with the results from previous research [ 14 , 23 , 24 ]. Among these phenolic acids, rosmarinic acid had the highest content and the highest contribution ratio to the antioxidant activity of WHT, which is a major component of Prunella vulgaris (a raw material of WHT) [ 25 ].…”

Implication of dietary phenolic acids on inflammation in cardiovascular disease

“…However, the mechanism behind this phenomenon is not yet well understood. On the other hand, a study of the effects of 12 weeks of protocatechuic acid supplementation on insulin and insulin growth factor-1 (IGF-1) in aging hypertension rats significantly improved endothelium-dependent vasorelaxation through the modulation of the PI3K--NOS--NO pathway (Masodsai et al, 2019).…”

Dietary Anti-Aging Polyphenols and Potential Mechanisms

“…Protocatechuic acid (PCA) is a major metabolite of green tea polyphenols with a strong antioxidant property [ 177 ]. Administration of PCA (200 mg/kg/day) significantly improved insulin- and IGF-1-induced vasorelaxation in aging spontaneously hypertensive rats via activating the PI3K/NOS/NO pathway [ 178 ]. Cyanidin-3-glucoside (Cy3G), a typical anthocyanin found in deep-colored plants [ 179 ], has been shown to promote eNOS protein expression and subsequently increase NO output in bovine artery endothelial cells [ 170 ].…”