title: Pomegranate extract decreases oxidative stress and alleviates mitochondrial impairment by activating AMPK-Nrf2 in hypothalamic paraventricular nucleus of spontaneously hypertensive rats.
abstract: High blood pressure, or "hypertension," is associated with high levels of oxidative stress in the paraventricular nucleus of the hypothalamus. While pomegranate extract is a known antioxidant that is thought to have antihypertensive effects, the mechanism whereby pomegranate extract lowers blood pressure and the tissue that mediates its antihypertensive effects are currently unknown. We have used a spontaneously hypertensive rat model to investigate the antihypertensive properties of pomegranate extract. We found that chronic treatment of hypertensive rats with pomegranate extract significantly reduced blood pressure and cardiac hypertrophy. Furthermore, pomegranate extract reduced oxidative stress, increased the antioxidant defense system, and decreased inflammation in the paraventricular nucleus of hypertensive rats. We determined that pomegranate extract reduced mitochondrial superoxide anion levels and increased mitochondrial function in the paraventricular nucleus of hypertensive rats by promoting mitochondrial biogenesis and improving mitochondrial dynamics and clearance. We went on to identify the AMPK-nuclear factor-erythroid 2 p45-related factor 2 (Nrf2) pathway as a mechanism whereby pomegranate extract reduces oxidative stress in the paraventricular nucleus to relieve hypertension. Our findings demonstrate that pomegranate extract alleviates hypertension by reducing oxidative stress and improving mitochondrial function in the paraventricular nucleus, and reveal multiple novel targets for therapeutic treatment of hypertension.
authors.affiliation: Department of Nutrition and Food Security, School of Public Health, Xi'an Jiaotong University, Xi'an 710061, China.|Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Wenyan
authors.initials: W
authors.lastname: Sun
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Chunhong
authors.initials: C
authors.lastname: Yan
authors.affiliation: The Sam and Ann Barshop Institute for Longevity and Aging Studies, Department of Cellular and Structural Biology, University of Texas Health Science Center San Antonio, San Antonio, Texas 78245, USA.
authors.forename: Bess
authors.initials: B
authors.lastname: Frost
authors.affiliation: Department of Central Laboratory, Shaanxi Provincial People's Hospital, Xi'an 710068, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Hou
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Mengqi
authors.initials: M
authors.lastname: Zeng
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Hongli
authors.initials: H
authors.lastname: Gao
authors.affiliation: Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Xi'an Jiaotong University Cardiovascular Research Center, Xi'an Jiaotong University, Xi'an 710061, China.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Kang
authors.affiliation: Center for Mitochondrial Biology and Medicine, The Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology and Frontier Institute of Science and Technology, Xi'an Jiaotong University, Xi'an 710049, China.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
mesh_terms: D055372:AMP-Activated Protein Kinases / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000737:chemistry / Q000494:pharmacology*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D029561:Lythraceae / Q000737:chemistry*; D008297:Male; D008928:Mitochondria / Q000378:metabolism* / Q000473:pathology; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects*; D010286:Paraventricular Hypothalamic Nucleus / Q000378:metabolism* / Q000473:pathology; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D000959:Antihypertensive Agents; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D010936:Plant Extracts; D055372:AMP-Activated Protein Kinases