PMID- 34076830 OWN - NLM STAT- MEDLINE DCOM- 20220207 LR - 20240226 IS - 1559-0259 (Electronic) IS - 1530-7905 (Linking) VI - 21 IP - 9 DP - 2021 Sep TI - Apigenin Improves Hypertension and Cardiac Hypertrophy Through Modulating NADPH Oxidase-Dependent ROS Generation and Cytokines in Hypothalamic Paraventricular Nucleus. PG - 721-736 LID - 10.1007/s12012-021-09662-1 [doi] AB - Apigenin, identified as 4', 5, 7-trihydroxyflavone, is a natural flavonoid compound that has many interesting pharmacological activities and nutraceutical potential including anti-inflammatory and antioxidant functions. Chronic, low-grade inflammation and oxidative stress are involved in both the initiation and progression of hypertension and hypertension-induced cardiac hypertrophy. However, whether or not apigenin improves hypertension and cardiac hypertrophy through modulating NADPH oxidase-dependent reactive oxygen species (ROS) generation and inflammation in hypothalamic paraventricular nucleus (PVN) has not been reported. This study aimed to investigate the effects of apigenin on hypertension in spontaneously hypertensive rats (SHRs) and its possible central mechanism of action. SHRs and Wistar-Kyoto (WKY) rats were randomly assigned and treated with bilateral PVN infusion of apigenin or vehicle (artificial cerebrospinal fluid) via osmotic minipumps (20 mug/h) for 4 weeks. The results showed that after PVN infusion of apigenin, the mean arterial pressure (MAP), heart rate, plasma norepinephrine (NE), Beta 1 receptor in kidneys, level of phosphorylation of PKA in the ventricular tissue and cardiac hypertrophy, perivascular fibrosis, heart level of oxidative stress, PVN levels of oxidative stress, interleukin 1beta (IL-1beta), interleukin 6 (IL-6), iNOS, monocyte chemotactic protein 1 (MCP-1), tyrosine hydroxylase (TH), NOX2 and NOX4 were attenuated and PVN levels of interleukin 10 (IL-10), superoxide dismutase 1 (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67) were increased. These results revealed that apigenin improves hypertension and cardiac hypertrophy in SHRs which are associated with the down-regulation of NADPH oxidase-dependent ROS generation and inflammation in the PVN. CI - (c) 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature. FAU - Gao, Hong-Li AU - Gao HL AD - Key Laboratory of Environment and Genes Related To Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China. FAU - Yu, Xiao-Jing AU - Yu XJ AD - Key Laboratory of Environment and Genes Related To Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China. FAU - Hu, Han-Bo AU - Hu HB AD - Key Laboratory of Environment and Genes Related To Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China. FAU - Yang, Qian-Wen AU - Yang QW AD - Key Laboratory of Environment and Genes Related To Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China. FAU - Liu, Kai-Li AU - Liu KL AD - Key Laboratory of Environment and Genes Related To Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China. FAU - Chen, Yan-Mei AU - Chen YM AD - Key Laboratory of Environment and Genes Related To Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China. FAU - Zhang, Yan AU - Zhang Y AD - Key Laboratory of Environment and Genes Related To Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China. FAU - Zhang, Dong-Dong AU - Zhang DD AD - Key Laboratory of Environment and Genes Related To Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China. FAU - Tian, Hua AU - Tian H AD - Key Laboratory of Environment and Genes Related To Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China. FAU - Zhu, Guo-Qing AU - Zhu GQ AD - Department of Physiology, Nanjing Medical University, Nanjing, 210029, China. FAU - Qi, Jie AU - Qi J AD - Key Laboratory of Environment and Genes Related To Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China. jie-qi@mail.xjtu.edu.cn. FAU - Kang, Yu-Ming AU - Kang YM AD - Key Laboratory of Environment and Genes Related To Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Xi'an Jiaotong University School of Basic Medical Sciences, Shaanxi Engineering and Research Center of Vaccine, Xi'an, 710061, China. ykang@mail.xjtu.edu.cn. LA - eng GR - 81770426/National Natural Science Foundation of China/ GR - 82070439/National Natural Science Foundation of China/ GR - 82070440/National Natural Science Foundation of China/ GR - xjh012019059/the Fundamental Research Funds for the Central Universities/ GR - xzd012019035/the Fundamental Research Funds for the Central Universities/ GR - PY3A044/the Fundamental Research Funds for the Central Universities/ GR - 2019M663750/Postdoctoral Research Foundation of China (CN)/ GR - 2020JM-079/Natural Science Basic Research Program of Shaanxi/ GR - 2019JQ-605/Natural Science Basic Research Program of Shaanxi/ PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20210602 PL - United States TA - Cardiovasc Toxicol JT - Cardiovascular toxicology JID - 101135818 RN - 0 (Anti-Inflammatory Agents) RN - 0 (Antihypertensive Agents) RN - 0 (Antioxidants) RN - 0 (Cytokines) RN - 0 (Reactive Oxygen Species) RN - 7V515PI7F6 (Apigenin) RN - EC 1.6.3.- (NADPH Oxidases) SB - IM MH - Animals MH - Anti-Inflammatory Agents/*pharmacology MH - Antihypertensive Agents/*pharmacology MH - Antioxidants/*pharmacology MH - Apigenin/*pharmacology MH - Arterial Pressure/drug effects MH - Cardiomegaly/*drug therapy/enzymology/physiopathology MH - Cytokines/*metabolism MH - Disease Models, Animal MH - Fibrosis MH - Hypertension/*drug therapy/enzymology/physiopathology MH - Male MH - Myocardium/metabolism/pathology MH - NADPH Oxidases/genetics/*metabolism MH - Oxidative Stress/*drug effects MH - Paraventricular Hypothalamic Nucleus/*drug effects/enzymology/physiopathology MH - Rats, Inbred SHR MH - Rats, Inbred WKY MH - Reactive Oxygen Species/*metabolism MH - Ventricular Function, Left/drug effects MH - Ventricular Remodeling/drug effects MH - Rats OTO - NOTNLM OT - Apigenin OT - Cytokines OT - Hypertension OT - Hypothalamic paraventricular nucleus OT - Oxidative stress EDAT- 2021/06/03 06:00 MHDA- 2022/02/08 06:00 CRDT- 2021/06/02 12:26 PHST- 2021/02/08 00:00 [received] PHST- 2021/05/17 00:00 [accepted] PHST- 2021/06/03 06:00 [pubmed] PHST- 2022/02/08 06:00 [medline] PHST- 2021/06/02 12:26 [entrez] AID - 10.1007/s12012-021-09662-1 [pii] AID - 10.1007/s12012-021-09662-1 [doi] PST - ppublish SO - Cardiovasc Toxicol. 2021 Sep;21(9):721-736. doi: 10.1007/s12012-021-09662-1. Epub 2021 Jun 2.