Quercetin Reverses Cardiac Systolic Dysfunction in Mice Fed with a High‐Fat Diet: Role of Angiogenesis

Abstract

Global consumption of high-fat diets (HFD) is associated with an increased incidence of cardiometabolic syndrome and cardiac injury, warranting identification of cardioprotective strategies. Cardioprotective effects of quercetin (Q) have mostly been evaluated in ischemic heart disease models and attributed to senolysis. We hypothesized that Q could alleviate murine cardiac damage caused by HFD by restoring the myocardial microcirculation. C57BL/6J mice were fed standard chow or HFD for 6 months and then treated with Q (50 mg/kg) or vehicle 5-day biweekly for 10 additional weeks. Left ventricular (LV) cardiac function was studied in vivo using magnetic resonance imaging, and intramyocardial fat deposition, microvascular density, oxidative stress, and senescence were analyzed ex vivo. Additionally, direct angiogenic effects of Q were studied in vitro in HUVECs. HFD increased body weight, heart weight, total cholesterol, and triglyceride levels, whereas Q normalized heart weight and triglycerides. LV ejection fraction was lower in HFD vs. control mice ( 56.20 ± 15.8 % vs. 73.38 ± 5.04 % , respectively, P < 0.05 ), but improved in HFD + Q mice ( 67.42 ± 7.50 % , P < 0.05 , vs. HFD). Q also prevented cardiac fat accumulation and reduced HFD-induced cardiac fibrosis, cardiomyocyte hypertrophy, oxidative stress, and vascular rarefaction. Cardiac senescence was not observed in any group. In vitro, ox-LDL reduced HUVEC tube formation activity, which Q effectively improved. Quercetin may directly induce angiogenesis and decrease myocardial oxidative stress, which might account for its cardioprotective effects in the murine HFD-fed murine heart independently from senolytic activity. Furthermore, its beneficial effects might be partly attributed to a decrease in plasma triglycerides and intramyocardial fat deposition.

Nrf2 Activation Mediates Antiallodynic Effect of Electroacupuncture on a Rat Model of Complex Regional Pain Syndrome Type-I through Reducing Local Oxidative Stress and Inflammation

“…The primary antibody was applied to immunostain the hindpaw skin sample sections: mouse anti-8-OHG (1 : 800, ab62623, Abcam), and the primary antibodies were applied to immunostain spinal cord sample sections: rabbit anti-c-Fos (1 : 800, #2250, CST), mouse anti-GFAP (1 : 1000, #c9205, Sigma), and mouse anti-OX42 (1 : 1000, #ab1211, Abcam). These antibodies have successfully been used in previous literatures for immunofluorescence staining of corresponding targets [28][29][30][31]. Then, the sample sections were labeled with the fluorescent secondary antibodies (Cy3-, Cy5-, or FITCconjugated) for 1 h at room temperature after washing in the dark.…”

Extracts from the Leaves of Cissus verticillata Ameliorate High-Fat Diet-Induced Memory Deficits in Mice

“…This may be associated with increased BDNF levels in the hippocampus. C. quadrangularis contains quercetin and ascorbic acid [ 49 ], which have therapeutic effects against HFD-induced liver damage [ 43 ], heart damage [ 50 ], and damage to blood vessels [ 51 ]. However, the analysis of functional compounds from CVEs remains to be elucidated.…”

Targeting Cardiovascular Diseases by Flavonols: An Update

“…Flavonols have numerous cardioprotective properties, such as platelet stabilization, anti-inflammatory, antidiabetic, antihypertensive, and hypocholesterolemic activity [ 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 ]. To the best of our knowledge, quercetin is the most widely distributed and well-known flavonol obtained from natural sources, as well as the best-studied flavonol, in both in vitro and in vivo studies [ 51 ].…”