Quercetin alleviates pulmonary angiogenesis in a rat model of hepatopulmonary syndrome

Abstract

Quercetin shows protective effects against hepatopulmonary syndrome (HPS), as demonstrated in a rat model. However, whether these effects involve pulmonary vascular angiogenesis in HPS remains unclear. Therefore, this study aimed to assess the effect of quercetin on pulmonary vascular angiogenesis and explore the underlying mechanisms. Male Sprague-Dawley rats weighing 200-250 g underwent sham operation or common bile duct ligation (CBDL). Two weeks after surgery, HIF-1α and NFκB levels were assessed in rat lung tissue by immunohistochemistry and western blot. Then, CBDL and sham-operated rats were further divided into 2 subgroups each to receive intraperitoneal administration of quercetin (50 mg/kg daily) or 0.2% Tween for two weeks: Sham (Sham+Tween; n=8), CBDL (CBDL+Tween; n=8), Q (Sham+quercetin; n=8), and CBDL+Q (CBDL+quercetin; n=8). After treatment, lung tissue specimens were assessed for protein (immunohistochemistry and western blot) and/or gene expression (quantitative real-time PCR) levels of relevant disease markers, including VEGFA, VEGFR2, Akt/p-Akt, HIF-1α, vWf, and IκB/p-IκB. Finally, arterial blood was analyzed for alveolar arterial oxygen pressure gradient (AaPO2). Two weeks after CBDL, HIF-1α expression in the lung decreased, but was gradually restored at four weeks. Treatment with quercetin did not significantly alter HIF-1α levels, but did reduce AaPO2 as well as lung tissue NF-κB activity, VEGFA gene and protein levels, Akt activity, and angiogenesis. Although hypoxia is an important feature in HPS, our findings suggest that HIF-1α was not the main cause for the VEGFA increase. Interestingly, quercetin inhibited pulmonary vascular angiogenesis in rats with HPS, with involvement of Akt/NF-κB and VEGFA/VEGFR-2 pathways.

Oxidative stress and cellular pathways of asthma and inflammation: Therapeutic strategies and pharmacological targets

“…The authors correlated the observed benefits with a potential role of Quercetin as a ROS and oxidant scavenger, along with its known ability to reduce inflammatory cytokine production (in particular TNFα) via modulation of NF-κβ1 and Iκβ pathways (Nair, et al, 2006). Moreover, supplementation of Quercetin in a rat model of hepatopulmonary syndrome showed anti-angiogenic effects associated with AKT/NF-κB and VEGFA/VEGFR-2 pathways (X. Li, et al, 2016).…”

A Systematic Study of Mechanism of Sargentodoxa cuneata and Patrinia scabiosifolia Against Pelvic Inflammatory Disease With Dampness-Heat Stasis Syndrome via Network Pharmacology Approach

“…Salvia Miltiorrhiza and puerarin improved the thrombus status by regulating the level of VEGF and the release of coagulation factors ( Hu et al, 2020 ). In a rat model of hepatopulmonary syndrome, quercetin predominantly inhibited pulmonary vascular angiogenesis by regulate VEGFA/VEGFR-2 pathways ( Li et al, 2016 ). Moreover, acacetin played an anti-inflammatory role by regulating the VEGFA ( Li and Ren, 2019 ).…”

Detection of antitumoral effects of quercetin through protein synthesis associated with argyrophilic nucleolar-regulating region

“…32,33 In the literature, there are articles reporting that the angiogenesis is decreased in the tumor groups as a result of factor VIII staining in studies with plants with antioxidant properties (Cornus mas L, curcumin, resveratrol, Viburnum opulus, quercetin). 8 –11,35 –37 Yang et al showed that AuNPs-Qu-5 inhibits angiogenesis and metastasis of quercetin in breast cancer cells tested by targeting the EGFR/ vascular endothelial growth factor receptor 2 (VEGFR-2) signal pathway. 5 In our study, the expression of FVIII in solid tumor masses was evaluated and the decrease in FVIII expression was found statistically significant in the groups given quercetin ( p < 0.05).…”