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University","award":["82270468"],"award-info":[{"award-number":["82270468"]}]},{"name":"Fundamental Research Funds for the Central University","award":["82070439"],"award-info":[{"award-number":["82070439"]}]},{"name":"Fundamental Research Funds for the Central University","award":["82070440"],"award-info":[{"award-number":["82070440"]}]},{"name":"Fundamental Research Funds for the Central University","award":["No. 2021JQ-068"],"award-info":[{"award-number":["No. 2021JQ-068"]}]},{"name":"Fundamental Research Funds for the Central University","award":["No. 2020GCZX-13"],"award-info":[{"award-number":["No. 2020GCZX-13"]}]},{"name":"Fundamental Research Funds for the Central University","award":["No. xzy012022045"],"award-info":[{"award-number":["No. xzy012022045"]}]},{"name":"Fundamental Research Funds for the Central University","award":["No. 2020A02"],"award-info":[{"award-number":["No. 2020A02"]}]},{"name":"Research Program of Xi\u2019an Children\u2019s Hospital","award":["82200473"],"award-info":[{"award-number":["82200473"]}]},{"name":"Research Program of Xi\u2019an Children\u2019s Hospital","award":["82270468"],"award-info":[{"award-number":["82270468"]}]},{"name":"Research Program of Xi\u2019an Children\u2019s Hospital","award":["82070439"],"award-info":[{"award-number":["82070439"]}]},{"name":"Research Program of Xi\u2019an Children\u2019s Hospital","award":["82070440"],"award-info":[{"award-number":["82070440"]}]},{"name":"Research Program of Xi\u2019an Children\u2019s Hospital","award":["No. 2021JQ-068"],"award-info":[{"award-number":["No. 2021JQ-068"]}]},{"name":"Research Program of Xi\u2019an Children\u2019s Hospital","award":["No. 2020GCZX-13"],"award-info":[{"award-number":["No. 2020GCZX-13"]}]},{"name":"Research Program of Xi\u2019an Children\u2019s Hospital","award":["No. xzy012022045"],"award-info":[{"award-number":["No. xzy012022045"]}]},{"name":"Research Program of Xi\u2019an Children\u2019s Hospital","award":["No. 2020A02"],"award-info":[{"award-number":["No. 2020A02"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>Background: Luteolin is widely distributed among a number of vegetal species worldwide. The pharmacological effects of luteolin are diverse and amongst antioxidant, free radical scavenging, and anti-inflammatory activities. Preliminary study showed that luteolin can ameliorate hypertension. However, the precise mechanism needs further investigation. There is no evidence that luteolin affects the paraventricular nucleus of the hypothalamus (PVN), a brain nucleus associated with a critical neural regulator of blood pressure. Our main aim was to explore the effect of luteolin on the PI3K\/Akt\/NF-\u03baB signaling pathway within the PVN of hypertensive rats. Methods: spontaneously hypertensive rats (SHRs) and corresponding normotensive control rats, the Wistar Kyoto (WKY) rats were divided into four groups and subsequently treated for 4 weeks with bilateral PVN injections of either luteolin (20 \u00b5g\/0.11 \u00b5L, volume: 0.11 \u00b5L\/h) or vehicle (artificial cerebrospinal fluid). Results: luteolin infusion to the PVN significantly decreased some hemodynamic parameters including the mean arterial pressure (MAP), heart rate (HR), circulating plasma norepinephrine (NE) and epinephrine (EPI). Additionally, there was a decrease in the expressions of the phosphatidylinositol 3-kinase (p-PI3K) and phosphorylated protein kinase-B (p-AKT), levels of reactive oxygen species (ROS), NAD(P)H oxidase subunit (NOX2, NOX4) in the PVN of SHRs. Meanwhile, the expression of inflammatory cytokines and the activity of nuclear factor \u03baB (NF-\u03baB) p65 in the PVN of SHRs were lowered. Furthermore, immunofluorescence results showed that injection of luteolin in the PVN reduced the expression of tyrosine hydroxylase (TH), and increased that of superoxide dismutase (SOD1) and the 67-kDa isoform of glutamate decarboxylase (GAD67) in the PVN of SHRs. Conclusion: Our novel findings revealed that luteolin lowered hypertension via inhibiting NF-\u03baB-mediated inflammation and PI3K\/Akt signaling pathway in the PVN.<\/jats:p>","DOI":"10.3390\/nu15030502","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T04:19:40Z","timestamp":1674101980000},"page":"502","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":55,"title":["Luteolin Attenuates Hypertension via Inhibiting NF-\u03baB-Mediated Inflammation and PI3K\/Akt Signaling Pathway in the Hypothalamic Paraventricular Nucleus"],"prefix":"10.3390","volume":"15","author":[{"given":"Hong-Li","family":"Gao","sequence":"first","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Shaanxi Engineering and Research Center of Vaccine, Xi\u2019an Jiaotong University School of Basic Medical Sciences, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Jing","family":"Yu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Shaanxi Engineering and Research Center of Vaccine, Xi\u2019an Jiaotong University School of Basic Medical Sciences, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Qi","family":"Feng","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Shaanxi Engineering and Research Center of Vaccine, Xi\u2019an Jiaotong University School of Basic Medical Sciences, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Shaanxi Engineering and Research Center of Vaccine, Xi\u2019an Jiaotong University School of Basic Medical Sciences, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han-Bo","family":"Hu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Shaanxi Engineering and Research Center of Vaccine, Xi\u2019an Jiaotong University School of Basic Medical Sciences, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Yang","family":"Zhao","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Shaanxi Engineering and Research Center of Vaccine, Xi\u2019an Jiaotong University School of Basic Medical Sciences, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia-Hao","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Shaanxi Engineering and Research Center of Vaccine, Xi\u2019an Jiaotong University School of Basic Medical Sciences, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kai-Li","family":"Liu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Shaanxi Engineering and Research Center of Vaccine, Xi\u2019an Jiaotong University School of Basic Medical Sciences, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Shaanxi Engineering and Research Center of Vaccine, Xi\u2019an Jiaotong University School of Basic Medical Sciences, Xi\u2019an 710061, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li-Yan","family":"Fu","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Shaanxi Engineering and Research Center of Vaccine, Xi\u2019an Jiaotong University School of Basic Medical Sciences, Xi\u2019an 710061, 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and Genes Related to Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Shaanxi Engineering and Research Center of Vaccine, Xi\u2019an Jiaotong University School of Basic Medical Sciences, Xi\u2019an 710061, China"},{"name":"Institute of Pediatric Diseases, Xi\u2019an Children\u2019s Hospital, Xi\u2019an 710003, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Ming","family":"Kang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Environment and Genes Related to Diseases of Education Ministry of China, Department of Physiology and Pathophysiology, Shaanxi Engineering and Research Center of Vaccine, Xi\u2019an Jiaotong University School of Basic Medical Sciences, Xi\u2019an 710061, 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