PMID- 32242611 OWN - NLM STAT- MEDLINE DCOM- 20210712 LR - 20210712 IS - 1941-7225 (Electronic) IS - 0895-7061 (Linking) VI - 33 IP - 7 DP - 2020 Jul 18 TI - Cinnamaldehyde Ameliorates Vascular Dysfunction in Diabetic Mice by Activating Nrf2. PG - 610-619 LID - 10.1093/ajh/hpaa024 [doi] AB - BACKGROUND: Oxidative stress is known to be associated with the development of diabetes. Cinnamaldehyde (CA) is a spice compound in cinnamon that enhances the antioxidant defense against reactive oxygen species (ROS) by activating nuclear factor erythroid-related factor 2 (Nrf2), which has been shown to have a cardioprotection effect. However, the relationship between CA and Nrf2 in diabetic vascular complications remains unclear. METHODS: Leptin receptor-deficient (db/db) mice were fed normal chow or diet containing 0.02% CA for 12 weeks. The vascular tone, blood pressure, superoxide level, nitric oxide (NO) production, renal morphology, and function were measured in each group. RESULTS: CA remarkably inhibited ROS generation, preserved NO production, increased phosphorylated endothelial nitric oxide synthase (p-eNOS), attenuated the upregulation of nitrotyrosine, P22 and P47 in aortas of db/db mice, and apparently ameliorated the elevation of type IV collagen, TGF-beta1, P22, and P47 in kidney of db/db mice. Feeding with CA improved endothelium-dependent relaxation of aortas and mesenteric arteries, and alleviated the remodeling of mesenteric arteries in db/db mice. Additionally, dietary CA ameliorated glomerular fibrosis and renal dysfunction in diabetic mice. Nrf2 and its targeted genes heme oxygenase-1 (HO-1) and quinone oxidoreductase-1 (NQO-1) were slightly increased in db/db mice and further upregulated by CA. However, these protective effects of CA were reversed in Nrf2 downregulation mice. CONCLUSIONS: A prolonged diet of CA protects against diabetic vascular dysfunction by inhibiting oxidative stress through activating of Nrf2 signaling pathway in db/db mice. CI - (c) American Journal of Hypertension, Ltd 2020. All rights reserved. For Permissions, please email: journals.permissions@oup.com. FAU - Wang, Peijian AU - Wang P AD - Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, PR China. AD - Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, PR China. AD - Key Laboratory of Aging and Vascular Homeostasis of Sichuan Higher Education Institutes, The First Affiliated Hospital, Chengdu Medical College, Chengdu, PR China. FAU - Yang, Yi AU - Yang Y AD - Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, PR China. AD - Key Laboratory of Aging and Vascular Homeostasis of Sichuan Higher Education Institutes, The First Affiliated Hospital, Chengdu Medical College, Chengdu, PR China. FAU - Wang, Dan AU - Wang D AD - Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, PR China. AD - Key Laboratory of Aging and Vascular Homeostasis of Sichuan Higher Education Institutes, The First Affiliated Hospital, Chengdu Medical College, Chengdu, PR China. FAU - Yang, Qiyuan AU - Yang Q AD - West China College of Stomatology, Sichuan University, Chengdu, PR China. FAU - Wan, Jindong AU - Wan J AD - Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, PR China. AD - Key Laboratory of Aging and Vascular Homeostasis of Sichuan Higher Education Institutes, The First Affiliated Hospital, Chengdu Medical College, Chengdu, PR China. FAU - Liu, Sen AU - Liu S AD - Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, PR China. AD - Key Laboratory of Aging and Vascular Homeostasis of Sichuan Higher Education Institutes, The First Affiliated Hospital, Chengdu Medical College, Chengdu, PR China. FAU - Zhou, Peng AU - Zhou P AD - Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, PR China. AD - Key Laboratory of Aging and Vascular Homeostasis of Sichuan Higher Education Institutes, The First Affiliated Hospital, Chengdu Medical College, Chengdu, PR China. FAU - Yang, Yongjian AU - Yang Y AD - Department of Cardiology, The General Hospital of Western Theater Command, Chengdu, PR China. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Hypertens JT - American journal of hypertension JID - 8803676 RN - 0 (Flavoring Agents) RN - 0 (NF-E2-Related Factor 2) RN - 0 (Nfe2l2 protein, mouse) RN - 0 (Reactive Oxygen Species) RN - 0 (TRPA1 Cation Channel) RN - 0 (Trpa1 protein, mouse) RN - 31C4KY9ESH (Nitric Oxide) RN - 7864XYD3JJ (Acrolein) RN - SR60A3XG0F (cinnamaldehyde) SB - IM CIN - Am J Hypertens. 2020 Jul 18;33(7):597-598. PMID: 32242620 MH - Acrolein/*analogs & derivatives/pharmacology/therapeutic use MH - Animals MH - Aorta/drug effects/metabolism MH - Diabetes Mellitus, Experimental/*complications/metabolism MH - Diabetic Angiopathies/*prevention & control MH - Drug Evaluation, Preclinical MH - Flavoring Agents/pharmacology/*therapeutic use MH - Kidney/drug effects MH - Male MH - Mice, Inbred C57BL MH - NF-E2-Related Factor 2/*metabolism MH - Nitric Oxide/metabolism MH - Oxidative Stress/drug effects MH - Reactive Oxygen Species/metabolism MH - TRPA1 Cation Channel/metabolism OTO - NOTNLM OT - blood pressure OT - cinnamaldehyde OT - diabetic vascular dysfunction OT - hypertension OT - nuclear factor erythroid-related factor 2 OT - oxidative stress EDAT- 2020/04/04 06:00 MHDA- 2021/07/13 06:00 CRDT- 2020/04/04 06:00 PHST- 2019/07/16 00:00 [received] PHST- 2019/11/05 00:00 [revised] PHST- 2020/04/01 00:00 [accepted] PHST- 2020/04/04 06:00 [pubmed] PHST- 2021/07/13 06:00 [medline] PHST- 2020/04/04 06:00 [entrez] AID - 5815427 [pii] AID - 10.1093/ajh/hpaa024 [doi] PST - ppublish SO - Am J Hypertens. 2020 Jul 18;33(7):610-619. doi: 10.1093/ajh/hpaa024.