title: Oleuropein improves mitochondrial function to attenuate oxidative stress by activating the Nrf2 pathway in the hypothalamic paraventricular nucleus of spontaneously hypertensive rats.
abstract: Hypertension is associated with increased reactive oxygen species (ROS) production in the paraventricular nucleus (PVN) of the hypothalamus. Oleuropein (OL) has a variety of biochemical roles, including antihypertensive and antioxidative functions. However, there have been few reports on the effects of OL on oxidative stress in the PVN on hypertension. In spontaneously hypertensive rats (SHR), eight-week administration of 60 mg/kg/day of OL significantly reduced blood pressure, pro-inflammatory cytokines and the expression of components of the renin-angiotensin system (RAS) compared with SHR rats treated with saline. Concomitantly, OL inhibited superoxide, and increased the antioxidant defense system in the PVN of SHR. We also found that OL increased mitochondrial biogenesis through mtDNA, PGC-1α, Complex II and Complex IV expression and regulated mitochondrial dynamics through the fusion-related protein Mfn2 and fision-related protein DRP1 to attenuate mitochondrial impairment. Furthermore, the phase II enzyme levels of Nrf2 and its downstream proteins NQO-1 and HO-1 were all markedly increased in the PVN of the OL-treated SHR group compared with the saline-treated SHR rats. Our findings demonstrate that OL administration can protect the PVN of the hypothalamus from oxidative stress by improving mitochondrial function through the activation of the Nrf2-mediated signaling pathway.
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: 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: Liang
authors.initials: L
authors.lastname: Yang
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: Hongbao
authors.initials: H
authors.lastname: Li
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: Jing
authors.initials: J
authors.lastname: Guo
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: Chanjuan
authors.initials: C
authors.lastname: Huo
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: Molin
authors.initials: M
authors.lastname: Wang
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: Yuwang
authors.initials: Y
authors.lastname: Miao
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. Electronic address: j.liu@mail.xjtu.edu.cn.
authors.forename: Jiankang
authors.initials: J
authors.lastname: Liu
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. Electronic address: ykang@mail.xjtu.edu.cn.
authors.forename: Yuming
authors.initials: Y
authors.lastname: Kang
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D006973:Hypertension / Q000188:drug therapy / Q000378:metabolism*; D057888:Iridoid Glucosides; D039823:Iridoids / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology*; D010286:Paraventricular Hypothalamic Nucleus / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017382:Reactive Oxygen Species / Q000037:antagonists & inhibitors / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology
chemical_list: D000959:Antihypertensive Agents; D057888:Iridoid Glucosides; D039823:Iridoids; D051267:NF-E2-Related Factor 2; C495637:Nfe2l2 protein, rat; D017382:Reactive Oxygen Species; C002769:oleuropein
keywords: Hypertension; Mitochondria; Nrf2; Oleuropein; Oxidative stress