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Oleuropein improves mitochondrial function to attenuate oxidative stress by activating the Nrf2 pathway in the hypothalamic paraventricular nucleus of spontaneously hypertensive rats.

Authors: Sun, Wenyan  Wang, Xin  Hou, Chen  Yang, Liang  Li, Hongbao  Guo, Jing  Huo, Chanjuan  Wang, Molin  Miao, Yuwang  Liu, Jiankang  Kang, Yuming 
Citation: Sun W, etal., Neuropharmacology. 2017 Feb;113(Pt A):556-566. doi: 10.1016/j.neuropharm.2016.11.010. Epub 2016 Nov 12.
Pubmed: (View Article at PubMed) PMID:27847271
DOI: Full-text: DOI:10.1016/j.neuropharm.2016.11.010

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.

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CRRD Object Information
CRRD ID: 12910764
Created: 2017-06-23
Species: All species
Last Modified: 2017-06-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.