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

Zhang,Fengwei; Feng,Jia; Zhang,Jingyu; Kang,Xin; Qian,Dun

doi:10.3892/etm.2020.9410

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

Authors:
- Fengwei Zhang
- Jia Feng
- Jingyu Zhang
- Xin Kang
- Dun Qian
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Affiliations: Department of Hepatobiliary Surgery, The Second Affiliated Hospital of Xi'an Medical University, Xi'an, Shaanxi 710038, P.R. China, Department of Endocrinology, Ninth Hospital of Xi'an, Xi'an, Shaanxi 710054, P.R. China, Department of Gastroenterology, Tangdu Hospital, Air Force Military Medical University, Xi'an, Shaanxi 710082, P.R. China, Department of Endocrinology, Xi'an International Medical Center Hospital, Xi'an, Shaanxi 710100, P.R. China, Department of Cardiology, Xi'an Lintong Development Zone Boren Hospital, Xi'an, Shaanxi 710600, P.R. China
Published online on: October 27, 2020 https://doi.org/10.3892/etm.2020.9410
Article Number: 280

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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.

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