Objective. This study aimed to evaluate the protective effect of kaempferol against myocardial ischemia/reperfusion (I/R) injury in rats.Method. Left ventricular developed pressure (LVDP) and its maximum up/down rate (±dp/dtmax) were recorded as myocardial function. Infarct size was detected with 2,3,5-triphenyltetrazolium chloride staining. Cardiomyocyte apoptosis was determined using terminal deoxynucleotidyl nick-end labeling (TUNEL). The levels of creatine kinase (CK), lactate dehydrogenase (LDH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione/glutathione disulfide (GSH/GSSG) ratio, and tumor necrosis factor-alpha (TNF-α) were determined using enzyme linked immunosorbent assay (ELISA). Moreover, total glycogen synthase kinase-3β(GSK-3β), phospho-GSK-3β(P-GSK-3β), precaspase-3, cleaved caspase-3, and cytoplasm cytochrome C were assayed using Western blot analysis.Results. Pretreatment with kaempferol significantly improved the recovery of LVDP and±dp/dtmax, as well as increased the levels of SOD and P-GSK-3βand GSH/GSSG ratio. However, the pretreatment reduced myocardial infarct size and TUNEL-positive cell rate, as well as decreased the levels of cleaved caspase-3, cytoplasm cytochrome C, CK, LDH, MDA, and TNF-α.Conclusion. These results suggested that kaempferol provides cardioprotection via antioxidant activity and inhibition of GSK-3βactivity in rats with I/R.

This study aims to evaluate the cardioprotective effects of astragalin against myocardial ischemia/reperfusion (I/R) injury in isolated rat heart. The cardioprotective effects of astragalin on myocardial I/R injury were investigated on Langendorff apparatus. Adult male Sprague‐Dawley rats were randomly divided into five groups. The results showed that astragalin pretreatment improved myocardial function. Compared with I/R group, lactate dehydrogenase (LDH) and creatine kinase (CK) activities in coronary flow decreased in astragalin pretreatment groups, whereas superoxide dismutase (SOD) activity and glutathione/glutathione disulfide (GSH/GSSG) ratio significantly increased. The levels of malondialdehyde (MDA), intracellular reactive oxygen species (ROS), tumor necrosis factor‐α (TNF‐α), and interleukin‐6 (IL‐6) decreased in astragalin‐treated groups. The infarct size (IS) and apoptosis rate in hearts from astragalin‐treated groups were lower than those in hearts from the I/R group. Western blot analysis also revealed that astragalin preconditioning significantly reduced Bax level, whereas Bcl‐2 was increased in the myocardium. Therefore, astragalin exhibited cardioprotective effects via its antioxidative, antiapoptotic, and anti‐inflammatory activities.

The aim of this study is to investigate both the efficacy and mechanism of action of kaempferide (Kae) as a therapy for the treatment of cardiovascular disease. A rat model of myocardial ischemia/reperfusion (I/R) injury was established by ligation of the left anterior descending coronary artery for 30 min followed by a 2 h perfusion. In our study, we show that Kae remarkably improved cardiac function, alleviated myocardial injury via a decrease in myocardial enzyme levels, and attenuated myocardial infarct size in a dose-dependent manner. In addition, preconditioning treatment with Kae was found to significantly decrease serum TNF-α, IL-6, C-reactive protein (CRP), MDA, and ROS levels, while it was found to increase serum levels of SOD. Nuclear factor erythroid 2-related factor 2 (Nrf2) and cleaved caspase-3 expression levels were observed to be downregulated, while phospho-Akt (p-Akt) and phospho-glycogen synthase kinase-3β (p-GSK-3β) expression levels were upregulated. However, cotreatment with LY294002 (a PI3K inhibitor) or TDZD-8 (a GSK-3β inhibitor) was found to abolish the above cardioprotective effects observed with the Kae treatment. The data presented in this study provides evidence that Kae attenuates I/R-induced myocardial injury through inhibition of the Nrf2 and cleaved caspase-3 signaling pathways via a PI3K/Akt/GSK 3β-dependent mechanism.

As metabolomics is widely used in the study of disease mechanisms, an increasing number of studies have found that metabolites play an important role in the occurrence of diseases. The aim of this study is to investigate the effects and mechanisms of quercetin in high-fat-sucrose diet (HFD)-induced nonalcoholic fatty liver disease (NAFLD) development using nontargeted metabolomics. A rat model of NAFLD was established by feeding with an HFD for 30 and 50 days. The results indicated quercetin exhibited hepatoprotective activity in 30-day HFD-induced NAFLD rats by regulating fatty acid related metabolites (adrenic acid, etc.), inflammation-related metabolites (arachidonic acid, etc.), oxidative stress-related metabolites (2-hydroxybutyric acid) and other differential metabolites (citric acid, etc.). However, quercetin did not improve NAFLD in the 50-day HFD; perhaps quercetin was unable to reverse the inflammation induced by a long-term high-fat diet. These data indicate that dietary quercetin may be beneficial to NAFLD in early stages. Furthermore, combining metabolomics and experimental approaches opens avenues to study the effects and mechanisms of drugs for complex diseases.

Background: Quercetin (Qr), isoquercitrin (IQ), and quercetin-3-O-β-D-glucuronide (QG) are powerful phytochemicals that have been shown to exhibit disease prevention and health promotion properties. However, there may exist transformations between Qr, IQ, and QG in vivo. And the pharmacokinetic profiles of Qr, IQ, and QG have not been systematically compared. The pharmacokinetics study would be helpful to better understand the pharmacological actions of them. Methods: Herein, we developed a reliable HPLC-MS method to compare the pharmacokinetics of Qr, IQ, and QG after separate (50 mg/kg) oral administration of them in rats, using puerarin as internal standard. The detection was performed using negative selected ion monitoring. This method was validated in terms of selectivity, linearity, precision, accuracy, extraction recovery, matrix effect, and stability; and shows reliabilities in monitoring the pharmacokinetic behaviors of these three compounds. Results: Our results showed that after separate oral administration of Qr, IQ, and QG, all of the compounds could be detected in plasma. In addition, QG could be detected in the Qr group; Qr and QG could be measured in the IQ group; and Qr could be found in rat plasma after 1.5 h of QG administration. Moreover, the AUC_0−t of Qr in the; Qr group (2,590.5 ± 987.9 mg/L*min), IQ group (2,212.7 ± 914.1 mg/L*min), and QG group (3,505.7 ± 1,565.0 mg/L*min) was larger than the AUC_0−t of QG in the; Qr group (1,550.0 ± 454.2 mg/L*min), IQ group (669.3 ± 188.3 mg/L*min), and QG group (962.7 ± 602.3 mg/L*min). The AUC_0−t of IQ was the lowest among all groups. Discussion: Quercetin, IQ, and QG can all be absorbed into plasma. A mutual transformation exists between Qr and QG, and IQ can be metabolized into Qr and QG in SD rats. These results would provide a meaningful basis for understanding the pharmacological actions of these three compounds.

Cardiovascular disease is the highest cause of death, and atherosclerosis (AS) is the primary pathogenesis of many cardiovascular diseases. In this study, we aim to investigate the possible pharmaceutical effects of Dendrobium huoshanense C. Z. Tang et S. J. Cheng polysaccharide (DHP) in AS. We fed zebrafish with high-cholesterol diet (HCD) to establish a zebrafish AS model and treated with DHP and observed plaque formation and neutrophil counts under a fluorescence microscope. Next, a parallel flow chamber was utilized to establish low shear stress- (LSS-) induced endothelial cell (EC) dysfunction model. We observed that DHP significantly improved HCD-induced lipid deposition, oxidative stress, and inflammatory response, mainly showing that DHP significantly increased superoxide dismutase (SOD) activity, decreased plaque formation, and decreased neutrophil recruitment and the levels of total cholesterol (TC), triglyceride (TG), malondialdehyde (MDA), and reactive oxygen species (ROS). Furthermore, DHP significantly improved LSS-induced oxidative stress and EC dysfunction. Our results indicated that DHP can exert treatment effects on AS, which may attribute to its hypolipidemic, antioxidant, anti-inflammatory activities and improving LSS-induced EC dysfunction. DHP has promising potential for further development as a functional natural medicine source targeted at AS prevention.