chrysin and Atherosclerosis

Cardiovascular diseases (CVDs) are the commonest cause of global mortality and morbidity. Atherosclerosis, the fundamental pathological manifestation of CVDs, is a complex process and is poorly managed both in terms of preventive and therapeutic intervention. Aberrant lipid metabolism and chronic inflammation play critical roles in the development of atherosclerosis. These processes can be targeted for effective management of the disease. Although managing lipid metabolism is in the forefront of current therapeutic approaches, controlling inflammation may also prove to be crucial for an efficient treatment regimen of the disease. Flavonoids, the plant-derived polyphenols, are known for their antiinflammatory properties. This review discusses the possible antiatherogenic role of 3 flavonoids, namely, chrysin, quercetin, and luteolin primarily known for their antiinflammatory properties.

Topics: Animals; Anti-Inflammatory Agents; Atherosclerosis; Biological Availability; Diet, Healthy; Flavonoids; Humans; Inflammation; Inflammation Mediators; Intestinal Absorption; Lipid Metabolism; Luteolin; Quercetin

Elevated plasma low-density lipoprotein (LDL) cholesterol level is a risk factor for developing atherosclerosis. Increased LDL receptor (LDLR) expression is expected to reduce the risk of atherosclerotic disease since hepatic LDLR is essential for clearing plasma LDL cholesterol. Here, we screened human LDLR promoter effectors and observed that extracts from peduncles of sweet cherry (Prunus avium) 'Sato-Nishiki' induce LDLR gene promoter activity. We used several analytical and chemical methods to show that chrysin 7-O-β-d-glucopyranoside (chrysin-7G) is one of the compounds that stimulate LDLR gene promoter activity in cherry peduncle extracts. Furthermore, synthetic chrysin-7G increased the expression and activity of LDLR. The chrysin-7G-mediated increase in LDLR expression and activity was completely abolished by treatment with an AMP-activated protein kinase (AMPK) inhibitor, compound C. These results indicate that chrysin-7G increases LDLR expression through AMPK activation and may be a useful compound that can be recycled from waste parts of agricultural products.

Topics: AMP-Activated Protein Kinases; Atherosclerosis; Humans; Lipoproteins, LDL; Liver; Receptors, LDL

Cardiometabolic diseases (CMD) have caused a great burden in terms of morbidity and mortality worldwide. The vicious cycle of CMD consists of type II diabetes, hypertension, dyslipidemia, obesity, and atherosclerosis. They have interlinked pathways, interacting and interconnecting with each other. The natural flavonoid chrysin has been shown to possess a broad spectrum of therapeutic activities for human health. Herein, we did an in-depth investigation of the novel mechanisms of chrysin's cardioprotection against cardiometabolic disorders. Studies have shown that chrysin protects the cardiovascular system by enhancing the intrinsic antioxidative defense system. This antioxidant property enhanced by chrysin protects against several risk factors of cardiometabolic disorders, including atherosclerosis, vascular inflammation and dysfunction, platelet aggregation, hypertension, dyslipidemia, cardiotoxicity, myocardial infarction, injury, and remodeling, diabetes-induced injuries, and obesity. Chrysin also exhibited anti-inflammatory mechanisms through inhibiting pro-inflammatory pathways, including NF-κB, MAPK, and PI3k/Akt. Furthermore, chrysin modulated NO, RAS, AGE/RAGE, and PPARs pathways which contributed to the risk factors of cardiometabolic disorders. Taken together, the mechanisms in which chrysin protects against cardiometabolic disorder are more than merely antioxidation and anti-inflammation in the cardiovascular system.

Topics: Anti-Inflammatory Agents; Antioxidants; Atherosclerosis; Cardiotoxicity; Diabetes Mellitus, Type 2; Flavonoids; Humans; Hypertension; Obesity; Phosphatidylinositol 3-Kinases

Chrysin (Chy) is known for various biological proprieties such as inhibitory effects on inflammation, cancer, oxidative stress, aging, and atherosclerosis. However, the hypolipidemic activity of Chy and its mechanistic action remains unclear in cardiovascular diseases (CVD). In this study, we focused on the hypolipidemic proprieties of Chy in hypercholesterolemia-induced atherosclerosis. Male Wistar rats (150-220 g) were divided into four groups as follows: Group I control was fed with standard laboratory chow. Rats in Group II were fed a high-fat diet (HFD) for 60 days. After 60 days of HFD, Group III rats received Chy (100 mg/kg body weight); Group IV rats received Atorvastatin (Atv; 10 mg/kg body weight) for 30 days. Biochemical studies showed Chy, Atv treatment decreased the activities of liver marker enzymes and the levels of Reactive Oxygen Species (ROS) and lipid profile. Gene expression analysis on nuclear factor erythroid 2-related factor 2 (Nrf2) and its regulated genes were significantly reduced in the intestine and increased in the aorta by Chy and Atv. Gut microbial species such as Bacteroidetes, Lactobacillus, Enterococcus, and Clostridium leptum copy numbers were significantly increased by Chy and Atv treatment. In addition, Chy and Atv modulated the expression of inflammatory genes including TLR4, TNFα, NLRP3, and IL-17 in the aorta and intestine compared with hypercholesterolemic control rats. Chy and Atv effectively increased the caspase-3 mRNA expression in the intestine, but these decreased in the aorta. The present study concludes that by reducing oxidative stress and increasing gut microbial colonization, Chy may provide an effective therapeutic approach for the prevention of hypercholesterolemia-mediated atherosclerosis. PRACTICAL APPLICATIONS: Our study focused on a therapeutic model representing the clinical presentation of atherosclerosis in humans. Statins are commonly used in the treatment of cardiovascular complications, patients with hypercholesterolemia face difficulties in the continuation of statin therapy. The reason for statin discontinuation has been associated with toxicological effects. It is necessary to investigate the potentiality of the natural compound as an alternative medicine to statin with fewer side effects. The main theme of our study is to compare the therapeutic potential of Chy and Atv. Chy is a natural bioflavonoid that could be considered as an alternative medicinal compound to statins and to avoid tox

Topics: Animals; Apoptosis; Atherosclerosis; Body Weight; Flavonoids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypercholesterolemia; Male; Oxidative Stress; Rats; Rats, Wistar

Hypercholesterolemia is one of the major risk factors that precipitate coronary heart disease and atherosclerosis. Oxidative stress is believed to contribute to the pathogenesis of hypercholesterolemic atherosclerosis; hence, various antioxidant compounds are being evaluated for potential anti-atherogenic effects. In the present study, the putative anti-atherogenic and antioxidant efficacy of a flavonoid, chrysin, was evaluated in an experimental model of atherosclerosis. In male, albino Wistar rats fed an atherogenic diet for 45 days and treated with saline, significantly higher mean levels of serum lipid profile parameters (total cholesterol, triglycerides, low-density, and very low-density lipoprotein cholesterol), lower mean levels of high-density lipoprotein cholesterol and higher mean serum levels of hepatic marker enzymes (aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, and lactate dehydrogenase) were observed when compared with the levels in rats fed a control diet. In addition, significantly lower mean hepatic levels of lipoprotein lipase, 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, antioxidant enzymes (catalase, superoxide dismutase, and glutathione peroxidase) and non-enzymatic antioxidants (reduced glutathione, and vitamins C and E), and a significantly higher mean level of hepatic malondialdehyde (MDA) were noted in comparison to the values in control rats. In atherogenic diet-fed rats that received chrysin orally (200 mg/kg b.wt) for 15 days, starting 30 days after the start of the atherogenic diet, significantly lower mean serum levels of lipid profile parameters (except for HDL-cholesterol which was elevated), hepatic marker enzymes, and significantly higher mean hepatic levels of LPL, HMG-CoA reductase, enzymatic, and non-enzymatic antioxidants and significantly lower mean levels of hepatic MDA were noted, compared to the values in atherogenic diet-fed, saline-treated rats. Histopathological studies appeared to suggest the protective effect of chrysin on the hepatic tissue and aorta of atherosclerotic rats. These results suggest that chrysin has anti-atherogenic potential in an experimental setting.

Topics: Animals; Antioxidants; Atherosclerosis; Biomarkers; Flavonoids; Hydroxymethylglutaryl CoA Reductases; Lipids; Lipoprotein Lipase; Liver; Male; Malondialdehyde; Rats; Rats, Wistar