PMID- 33472479 OWN - NLM STAT- MEDLINE DCOM- 20210514 LR - 20210514 IS - 1473-2300 (Electronic) IS - 0300-0605 (Print) IS - 0300-0605 (Linking) VI - 49 IP - 1 DP - 2021 Jan TI - Dietary chlorogenic acid ameliorates oxidative stress and improves endothelial function in diabetic mice via Nrf2 activation. PG - 300060520985363 LID - 10.1177/0300060520985363 [doi] LID - 0300060520985363 AB - OBJECTIVES: Chlorogenic acid (CGA) is an antioxidant dietary factor. We investigated the effects of CGA on endothelial cell dysfunction in diabetic mice and the mechanistic role of nuclear factor erythroid-related factor 2 (Nrf2) in the antioxidant effect of CGA. METHODS: Diabetic (db/db) mice were fed normal chow or chow containing 0.02% CGA for 12 weeks. Human umbilical vein endothelial cells (HUVECs) and mouse aortas were treated with normal or high glucose. RESULTS: CGA treatment induced upregulation of Nrf2 in HUVECs in a dose-dependent manner. CGA pretreatment prevented reactive oxygen species generation and preserved nitric oxide bioavailability in HUVECs and aortas from wild-type but not Nrf2(-/-) mice. CGA improved endothelium-dependent relaxation in high glucose-treated aortas from wild-type and db/db mice, but not Nrf2(-/-) mice. Dietary CGA improved endothelium-dependent relaxation in db/db mice. CONCLUSIONS: CGA ameliorates endothelial dysfunction in diabetic mice through activation of the Nrf2 anti-oxidative pathway. FAU - Wang, Dan AU - Wang D AD - Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. AD - Key Laboratory of Aging and Vascular Homeostasis, Sichuan Higher Education Institute, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. FAU - Hou, Jixin AU - Hou J AD - Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. AD - Key Laboratory of Aging and Vascular Homeostasis, Sichuan Higher Education Institute, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. FAU - Wan, Jindong AU - Wan J AD - Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. AD - Key Laboratory of Aging and Vascular Homeostasis, Sichuan Higher Education Institute, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. FAU - Yang, Yi AU - Yang Y AD - Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. AD - Key Laboratory of Aging and Vascular Homeostasis, Sichuan Higher Education Institute, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. FAU - Liu, Sen AU - Liu S AD - Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. AD - Key Laboratory of Aging and Vascular Homeostasis, Sichuan Higher Education Institute, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. FAU - Li, Xiaoqing AU - Li X AD - School of Pharmacy, Chengdu Medical College, Chengdu, Sichuan, China. FAU - Li, Wenzhang AU - Li W AD - Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. AD - Key Laboratory of Aging and Vascular Homeostasis, Sichuan Higher Education Institute, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. FAU - Dai, Xiaozhen AU - Dai X AD - School of Biological Sciences and Technology, Chengdu Medical College, Chengdu, Sichuan, China. FAU - Zhou, Peng AU - Zhou P AD - Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. AD - Key Laboratory of Aging and Vascular Homeostasis, Sichuan Higher Education Institute, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. FAU - Liu, Weihua AU - Liu W AD - Department of Scientific Research, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. FAU - Wang, Peijian AU - Wang P AUID- ORCID: 0000-0002-3622-4538 AD - Department of Cardiology, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. AD - Key Laboratory of Aging and Vascular Homeostasis, Sichuan Higher Education Institute, The First Affiliated Hospital, Chengdu Medical College, Chengdu, Sichuan, China. LA - eng PT - Journal Article PL - England TA - J Int Med Res JT - The Journal of international medical research JID - 0346411 RN - 0 (NF-E2-Related Factor 2) RN - 318ADP12RI (Chlorogenic Acid) SB - IM MH - Animals MH - Chlorogenic Acid/metabolism/pharmacology MH - *Diabetes Mellitus, Experimental/drug therapy MH - Endothelium, Vascular MH - Mice MH - *NF-E2-Related Factor 2/metabolism MH - Oxidative Stress PMC - PMC7829538 OTO - NOTNLM OT - Chlorogenic acid OT - diabetes OT - endothelial dysfunction OT - endothelium OT - nuclear factor E2-related factor 2 OT - oxidative stress COIS- Declaration of conflicting interest: The authors declare that there is no conflict of interest. EDAT- 2021/01/22 06:00 MHDA- 2021/05/15 06:00 PMCR- 2021/01/20 CRDT- 2021/01/21 05:23 PHST- 2021/01/21 05:23 [entrez] PHST- 2021/01/22 06:00 [pubmed] PHST- 2021/05/15 06:00 [medline] PHST- 2021/01/20 00:00 [pmc-release] AID - 10.1177_0300060520985363 [pii] AID - 10.1177/0300060520985363 [doi] PST - ppublish SO - J Int Med Res. 2021 Jan;49(1):300060520985363. doi: 10.1177/0300060520985363.