Oleuropein improves mitochondrial function to attenuate oxidative stress by activating the Nrf2 pathway in the hypothalamic paraventricular nucleus of spontaneously hypertensive rats
| Autor: | Liang Yang, Hong-Bao Li, Jing Guo, Yu-Wang Miao, Yu-Ming Kang, Chan-Juan Huo, Jiankang Liu, Wenyan Sun, Chen Hou, Xin Wang, Molin Wang |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
Male
0301 basic medicine endocrine system medicine.medical_specialty Antioxidant NF-E2-Related Factor 2 medicine.medical_treatment Iridoid Glucosides MFN2 Mitochondrion medicine.disease_cause Rats Inbred WKY 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound Rats Inbred SHR Internal medicine medicine Animals Iridoids Antihypertensive Agents Pharmacology chemistry.chemical_classification Reactive oxygen species Superoxide Mitochondria Rats Oxidative Stress 030104 developmental biology Endocrinology chemistry Mitochondrial biogenesis Hypothalamus Hypertension Reactive Oxygen Species Oxidative stress Paraventricular Hypothalamic Nucleus Signal Transduction |
| Zdroj: | Neuropharmacology. 113:556-566 |
| ISSN: | 0028-3908 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect