Chrysin attenuates high-fat-diet-induced myocardial oxidative stress via upregulating eNOS and Nrf2 target genes in rats

Sambandam, Yuvaraj; Ramprasath, Tharmarajan; Saravanan, Balakrishnan; Vasudevan, Varadaraj; Sundaresan, Sivapatham; Selvam, Govindan Sadasivam

doi:10.1007/s11010-021-04105-5

Cited by 17 publications

(11 citation statements)

References 35 publications

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“…The weight gain, high liver index, and elevated TG levels (both in the serum and liver tissue) observed in the current study were markedly reduced by chrysin supplementation. These data are in agreement with those of Pai et al [ 33 ] and Pushpavalli et al [ 57 ] and support the findings concerning the antihyperlipidemic effects of chrysin [ 26 , 27 , 58 – 60 ], which is exerted probably via elevating the activity of lipoprotein lipase (LPL) which hydrolyses the extra TG [ 27 ] and downregulating the action of the lipogenic enzymes, e.g., fatty acid synthase [ 59 ].…”

Section: Discussionsupporting

confidence: 90%

“…Here, we reported that chrysin (25 and 50 mg/kg) significantly ameliorated this imbalance, suggesting increased scavenging ability of free radicals and the hepatoprotective effect via antioxidant properties. The chrysin's antioxidant activity has been reported in several animal models via different mechanisms [ 50 – 53 , 60 , 63 – 65 ].…”

Section: Discussionmentioning

confidence: 99%

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Chrysin Attenuates Fructose-Induced Nonalcoholic Fatty Liver in Rats via Antioxidant and Anti-Inflammatory Effects: The Role of Angiotensin-Converting Enzyme 2/Angiotensin (1-7)/Mas Receptor Axis

Attia

Albekairi

Albdeirat

et al. 2022

Oxidative Medicine and Cellular Longevity

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Aim. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome, and if untreated, it may propagate into end-stage liver disease. The classical arm of the renin-angiotensin system (RAS) has a fundamental role in triggering oxidative stress and inflammation, which play potential roles in the pathogenesis of NAFLD. However, the nonclassical alternative axis of RAS, angiotensin- (Ang-) converting enzyme 2 (ACE2)/Ang (1-7)/Mas receptor, opposes the actions of the classical arm, mitigates the metabolic dysfunction, and improves hepatic lipid metabolism rendering it a promising protective target against NAFLD. The current study is aimed at investigating the impact of chrysin, a well-known antioxidant flavonoid, on this defensive RAS axis in NAFLD. Methods. Rats were randomly distributed and treated daily for eight weeks as follows: the normal control, chrysin control (50 mg/kg, p.o), NAFLD group (received 20% fructose in drinking water), and treated groups (25 and 50 mg/kg chrysin given orally and concomitantly with fructose). Diminazene aceturate (DIZE) (15 mg/kg, s.c.) was used as a reference ACE2 activator. Key Findings. High fructose induced significant weight gain, hepatocyte degeneration with fat accumulation, and inflammatory cell infiltration (as examined by H&E staining). This was accompanied by a substantial increase in liver enzymes, glucose, circulating and hepatic triglycerides, lipid peroxides, inflammatory cytokines, and Ang II (the main component of classical RAS). At the same time, protein levels of ACE2, Ang (1-7), and Mas receptors were markedly reduced. Chrysin (25 and 50 mg/kg) significantly ameliorated these abnormalities, with a prominent effect of the dose of 50 mg/kg over DIZE and the lower dose in improving ACE2, Ang (1-7), and Mas. Significance. Chrysin is a promising efficient protective remedy against NAFLD; mechanisms include the activation of ACE2/Ang (1-7)/Mas axis.

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Section: Discussionsupporting

confidence: 90%

Section: Discussionmentioning

confidence: 99%

Chrysin Attenuates Fructose-Induced Nonalcoholic Fatty Liver in Rats via Antioxidant and Anti-Inflammatory Effects: The Role of Angiotensin-Converting Enzyme 2/Angiotensin (1-7)/Mas Receptor Axis

Attia

Albekairi

Albdeirat

et al. 2022

Oxidative Medicine and Cellular Longevity

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“…HFD increased the myocardium damage, with increased production of ROS and decreased expression of antioxidant levels (Yuvaraj et al, 2021). Similarly, the present study found significantly increased ROS production with downregulated expression of Nrf2, SOD, and Catalase genes compared with hypercholesterolemic control rats.…”

Section: Discussionsupporting

confidence: 82%

Chrysin reduces hypercholesterolemia‐mediated atherosclerosis through modulating oxidative stress, microflora, and apoptosis in experimental rats

Sambandam

Sasikumar

Puhari

et al. 2022

Journal of Food Biochemistry

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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 toxicity problems associated with statins. Chy is a bioflavonoid present in Passiflora caerulea (blue passion flower), Oroxylum indicum (Indian trumpet flower), Pelargonium crispum, propolis, and honey. Consuming Chy‐rich foods will reduce hypercholesterolemia‐mediated cardiovascular complications. Overall, the present studies provided a key to developing bioactive compounds‐based foods for CVD patients.

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“…The administration of chrysin in mice challenged with LPS (lipopolysaccharide) reduced the development of lung injuries by suppressing the inositol-requiring enzyme 1α/thioredoxin interaction protein/nucleotidebinding oligomerization domain-like receptor protein 3 pathway [56]. In rats, it prevented the myocardial complications of hypercholesterolemia-triggered oxidative stress through the activation of endothelial nitric oxide synthase and Nrf2 target genes such as SOD (superoxide dismutase) and catalase [57]. Furthermore, chrysin significantly inhibited proliferation and induced apoptosis on human cervical cancer cells [58] and colorectal cancer cells [59] by modulating various apoptotic genes and AKT/MAPK pathway genes.…”

Section: Flavonoids and Chronic Inflammationmentioning

confidence: 99%

Flavonoids: A Myth or a Reality for Cancer Therapy?

et al. 2021

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Nutraceuticals are biologically active molecules present in foods; they can have beneficial effects on health, but they are not available in large enough quantities to perform this function. Plant metabolites, such as polyphenols, are widely diffused in the plant kingdom, where they play fundamental roles in plant development and interactions with the environment. Among these, flavonoids are of particular interest as they have significant effects on human health. In vitro and/or in vivo studies described flavonoids as essential nutrients for preventing several diseases. They display broad and promising bioactivities to fight cancer, inflammation, bacterial infections, as well as to reduce the severity of neurodegenerative and cardiovascular diseases or diabetes. Therefore, it is not surprising that interest in flavonoids has sharply increased in recent years. More than 23,000 scientific publications on flavonoids have described the potential anticancer activity of these natural molecules in the last decade. Studies, in vitro and in vivo, show that flavonoids exhibit anticancer properties, and many epidemiological studies confirm that dietary intake of flavonoids leads to a reduced risk of cancer. This review provides a glimpse of the mechanisms of action of flavonoids on cancer cells.

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Chrysin attenuates high-fat-diet-induced myocardial oxidative stress via upregulating eNOS and Nrf2 target genes in rats

Cited by 17 publications

References 35 publications

Chrysin Attenuates Fructose-Induced Nonalcoholic Fatty Liver in Rats via Antioxidant and Anti-Inflammatory Effects: The Role of Angiotensin-Converting Enzyme 2/Angiotensin (1-7)/Mas Receptor Axis

Chrysin Attenuates Fructose-Induced Nonalcoholic Fatty Liver in Rats via Antioxidant and Anti-Inflammatory Effects: The Role of Angiotensin-Converting Enzyme 2/Angiotensin (1-7)/Mas Receptor Axis

Chrysin reduces hypercholesterolemia‐mediated atherosclerosis through modulating oxidative stress, microflora, and apoptosis in experimental rats

Flavonoids: A Myth or a Reality for Cancer Therapy?

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