Quercetin modulates AMPK/SIRT1/NF‑κB signaling to inhibit inflammatory/oxidative stress responses in diabetic high fat diet‑induced atherosclerosis in the rat carotid artery

Abstract

Inflammation and oxidative stress serve interrelated roles in the development of atherosclerosis and other vascular diseases. Quercetin has been previously reported to exhibit numerous beneficial properties towards several metabolic conditions and cardiovascular disease. The present study aimed to evaluate the effects of quercetin on the 5'adenosine monophosphate-activated protein kinase (AMPK)/sirtuin 1 (SIRT1)/NF-κB signaling pathway and inflammatory/oxidative stress response in diabetic-induced atherosclerosis in the carotid artery of rats. Male Wistar rats were used to create a diabetes-induced atherosclerosis model by the administration of high fat diet (HFD) with streptozotocin, which lasted for 8 weeks. Control and diabetic rats received quercetin (30 mg/kg/day; orally) for the last 2 weeks of the diabetic period. Plasma lipid profile and vascular levels of oxidative stress markers, inflammatory cytokines, NF-κB signaling proteins and SIRT1 expression were evaluated using ELISA and western blotting. Quercetin treatment in HFD diabetic rats was reported to improve the lipid profile and reduce the number of atherosclerotic lesions, atherogenic index and malondialdehyde levels, whilst increasing the activity of enzymatic antioxidants in the carotid artery. Additionally, the inflammatory response was suppressed by quercetin administration, as indicated by the reduced NF-κB and IL-1β levels, and increased IL-10 levels. Furthermore, SIRT1 expression was revealed to be significantly increased in response to quercetin treatment compared with non-treated HFD rats. However, these effects of quercetin were abolished or reversed by the administration of compound-C (0.2 mg/kg), a specific AMPK blocker, in HFD rats. Therefore, quercetin may have promising potential in ameliorating atherosclerotic pathophysiology in the rat carotid artery by inhibiting oxidative stress and inflammatory responses mechanistically by modulating the AMPK/SIRT1/NF-κB signaling pathway.

Diabetes Mellitus and Cardiovascular Diseases: Nutraceutical Interventions Related to Caloric Restriction

“…In detail, Zhang et al have observed that QE treatment in obese diabetic rats improves the lipid metabolism and reduces the number of atherosclerotic lesions, enhancing the activity of antioxidant enzymes in the carotid artery. They demonstrated, using a specific AMPK inhibitor (compound-C), that QE mitigates atherosclerotic damages, activating the AMPK/SIRT1/NF-κB signaling pathway [174].…”

Research on the Mechanism of Wuwei Yuganzi San in the Treatment of Coronary Heart Disease Based on Network Pharmacology

“…Among them, quercetin is a avonoid ingredient and exists widely in nature. Research showed that quercetin modulated AMPK/SIRT1/NF-κB signaling pathway [37] or JAK2/STAT3 pathway [38] to inhibit cell apoptosis and oxidative stress, reduce myocardial infarction size, improve ventricular remodeling and cardiac functionrelated biochemical indexes, and promote the recovery of cardiac blood ow. And a double-blind, placebocontrolled, randomized clinical trial demonstrated signi cantly elevated total antioxidant capacity [39].…”

Dynamic Alterations of the Distal Intestinal Microbiota, Transcriptome, and Metabolome of Hybrid Grouper by β -Conglycinin With Reconciliations by Sodium Butyrate in Feed

“…Our results showed that high-dose 7S had negative effects on "cysteine and methionine metabolism, " "AMPK signaling pathway, " "galactose metabolism, " "starch and sucrose metabolism, " "ABC transporters, " and "amino sugar and nucleotide sugar metabolism" and a positive effect on "ferroptosis." Quercetin could inhibit oxidative stress and inflammatory responses by regulating the AMPK/SIRT1/NF-κB signaling pathway (Zhang et al, 2020), indicating that high-dose 7S might inhibit the absorption and utilization of carbohydrates in the feed of hybrid grouper, resulting in insufficient energy supply. Ferroptosis is caused by the accumulation of reactive oxygen radicals on membrane lipids because of the failure of glutathione peroxidase activity (Doll et al, 2016).…”