Dose-related Effects of Resveratrol in Different Models of Pulmonary Arterial Hypertension: A Systematic Review

Abstract

Background: Pulmonary arterial hypertension (PAH) is a severe and progressive disease of pulmonary arterioles. This pathology is characterized by elevation of the pulmonary vascular resistance and pulmonary arterial pressure, leading to right heart failure and death. Studies have demonstrated that resveratrol possesses a protective effect in the mechanisms related to the genesis of the PAH-induced by different models. Objective: This study aimed to investigate the dose-related effects of resveratrol in different models of pulmonary arterial hypertension. Methods: To identify eligible papers, we performed a systematic literature search on Scielo, PubMed, and Scholar Google. The research was limited to articles written in English in the last 10 years. We use the following descriptors to search: Pulmonary Arterial Hypertension and Resveratrol, OR Resveratrol, and Animal models of Pulmonary Arterial Hypertension, OR Resveratrol, and in vitro models of Pulmonary Arterial Hypertension. Results: 1724 studies were identified through the descriptors employed, fifty-five studies with different models of pulmonary arterial hypertension were selected for the full review, forty-four were excluded after application of exclusion and inclusion criteria, totalizing eleven studies included in this systematic review. Conclusion: The results showed that resveratrol, at low and high doses, protects in a dose-dependent manner against the development of PAH induced through monocrotaline, normoxia and hypoxia models. In addition to having chemopreventive, anti-inflammatory, antioxidant and antiproliferative properties. In the case of PAH-related myocardial injury, resveratrol protects cells from apoptosis, thus working as an antiapoptotic agent.

Resveratrol Improves Bnip3-Related Mitophagy and Attenuates High-Fat-Induced Endothelial Dysfunction

“…For example, resveratrol enhances the expression of Nrf2 in myocardium and, thus, alleviates myocardial ischemia-reperfusion injury (Schreiber et al, 2019;Xu et al, 2019). Administration of resveratrol is shown to retard the progression of pulmonary arterial hypertension (Ferreira et al, 2019). Treatment with resveratrol attenuates isoprenaline-related cardiotoxicity in Wistar rats (Sammeturi et al, 2019).…”

Oral administration of resveratrol reduces oxidative stress generated in the hippocampus of Wistar rats in response to consumption of ethanol

“…The reason why a single dose of resveratrol (10 mg/Kg/day) is used in our study is that, to the best of our knowledge, there is no conclusive evidence of what would be the best dose of resveratrol for health benefits; the more recent studies in animal models show that both low (<20 mg/Kg/day) and high (>30 mg/Kg/day) doses of resveratrol have similar effect sizes on clinical outcomes such as ischemia/reperfusion injury ( Xue et al, 2022 ) and pulmonary arterial hypertension ( Ferreira et al, 2020 ). Unfortunately, at the date of writing this study, there is no meta-analytic evidence on the most useful dose for the protection of oxidative stress, so we consider it widely useful to evaluate a single low dose to reduce the confounding factor of dose-dependence.…”

Systematic analysis of nutrigenomic effects of polyphenols related to cardiometabolic health in humans – Evidence from untargeted mRNA and miRNA studies

“…The effects of polyphenols on hypertension and vascular dysfunction as key components of metabolic syndrome have been widely studied. Bioactives under investigation include hesperidin (Valls et al, 2021), anthocyanins (Igwe et al, 2019), grape seed polyphenols (Schön et al, 2021), or resveratrol (Breuss et al, 2019) (Ferreira et al, 2020), for which global genomic effects have been reported in publications included in our study. Meta-analyses of human intervention studies showed modest effects of various polyphenols or polyphenol-rich foods on blood pressure when compared with antihypertensive drugs (Zhang et al, 2016) (Sahebkar et al, 2017).…”