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Luteolin Attenuates Hypertension via Inhibiting NF-κB-Mediated Inflammation and PI3K/Akt Signaling Pathway in the Hypothalamic Paraventricular Nucleus

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,...

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Autores principales: Gao, Hong-Li, Yu, Xiao-Jing, Feng, Yu-Qi, Yang, Yu, Hu, Han-Bo, Zhao, Yu-Yang, Zhang, Jia-Hao, Liu, Kai-Li, Zhang, Yan, Fu, Li-Yan, Li, Ying, Qi, Jie, Qiao, Jin-An, Kang, Yu-Ming
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9921115/
https://www.ncbi.nlm.nih.gov/pubmed/36771206
http://dx.doi.org/10.3390/nu15030502
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author Gao, Hong-Li
Yu, Xiao-Jing
Feng, Yu-Qi
Yang, Yu
Hu, Han-Bo
Zhao, Yu-Yang
Zhang, Jia-Hao
Liu, Kai-Li
Zhang, Yan
Fu, Li-Yan
Li, Ying
Qi, Jie
Qiao, Jin-An
Kang, Yu-Ming
author_facet Gao, Hong-Li
Yu, Xiao-Jing
Feng, Yu-Qi
Yang, Yu
Hu, Han-Bo
Zhao, Yu-Yang
Zhang, Jia-Hao
Liu, Kai-Li
Zhang, Yan
Fu, Li-Yan
Li, Ying
Qi, Jie
Qiao, Jin-An
Kang, Yu-Ming
author_sort Gao, Hong-Li
collection PubMed
description 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-κB 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 µg/0.11 µL, volume: 0.11 µL/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 κB (NF-κB) 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-κB-mediated inflammation and PI3K/Akt signaling pathway in the PVN.
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spelling pubmed-99211152023-02-12 Luteolin Attenuates Hypertension via Inhibiting NF-κB-Mediated Inflammation and PI3K/Akt Signaling Pathway in the Hypothalamic Paraventricular Nucleus Gao, Hong-Li Yu, Xiao-Jing Feng, Yu-Qi Yang, Yu Hu, Han-Bo Zhao, Yu-Yang Zhang, Jia-Hao Liu, Kai-Li Zhang, Yan Fu, Li-Yan Li, Ying Qi, Jie Qiao, Jin-An Kang, Yu-Ming Nutrients Article 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-κB 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 µg/0.11 µL, volume: 0.11 µL/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 κB (NF-κB) 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-κB-mediated inflammation and PI3K/Akt signaling pathway in the PVN. MDPI 2023-01-18 /pmc/articles/PMC9921115/ /pubmed/36771206 http://dx.doi.org/10.3390/nu15030502 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Gao, Hong-Li
Yu, Xiao-Jing
Feng, Yu-Qi
Yang, Yu
Hu, Han-Bo
Zhao, Yu-Yang
Zhang, Jia-Hao
Liu, Kai-Li
Zhang, Yan
Fu, Li-Yan
Li, Ying
Qi, Jie
Qiao, Jin-An
Kang, Yu-Ming
Luteolin Attenuates Hypertension via Inhibiting NF-κB-Mediated Inflammation and PI3K/Akt Signaling Pathway in the Hypothalamic Paraventricular Nucleus
title Luteolin Attenuates Hypertension via Inhibiting NF-κB-Mediated Inflammation and PI3K/Akt Signaling Pathway in the Hypothalamic Paraventricular Nucleus
title_full Luteolin Attenuates Hypertension via Inhibiting NF-κB-Mediated Inflammation and PI3K/Akt Signaling Pathway in the Hypothalamic Paraventricular Nucleus
title_fullStr Luteolin Attenuates Hypertension via Inhibiting NF-κB-Mediated Inflammation and PI3K/Akt Signaling Pathway in the Hypothalamic Paraventricular Nucleus
title_full_unstemmed Luteolin Attenuates Hypertension via Inhibiting NF-κB-Mediated Inflammation and PI3K/Akt Signaling Pathway in the Hypothalamic Paraventricular Nucleus
title_short Luteolin Attenuates Hypertension via Inhibiting NF-κB-Mediated Inflammation and PI3K/Akt Signaling Pathway in the Hypothalamic Paraventricular Nucleus
title_sort luteolin attenuates hypertension via inhibiting nf-κb-mediated inflammation and pi3k/akt signaling pathway in the hypothalamic paraventricular nucleus
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9921115/
https://www.ncbi.nlm.nih.gov/pubmed/36771206
http://dx.doi.org/10.3390/nu15030502
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