Scutellarin Attenuates Hypertension-Induced Expression of Brain Toll-Like Receptor 4/Nuclear Factor Kappa B

Hypertension is associated with low-grade inflammation, and Toll-like receptor 4 (TLR4) has been shown to be linked to the development and maintenance of hypertension. This study aimed to investigate the effects of scutellarin (administered by oral gavage daily for 2 weeks) on brain TLR4/nuclear fac...

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Main Authors: Xingyong Chen, Xiaogeng Shi, Xu Zhang, Huixin Lei, Simei Long, Huanxing Su, Zhong Pei, Ruxun Huang
Format: Article
Language:English
Published: Wiley 2013-01-01
Series:Mediators of Inflammation
Online Access:http://dx.doi.org/10.1155/2013/432623
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author Xingyong Chen
Xiaogeng Shi
Xu Zhang
Huixin Lei
Simei Long
Huanxing Su
Zhong Pei
Ruxun Huang
author_facet Xingyong Chen
Xiaogeng Shi
Xu Zhang
Huixin Lei
Simei Long
Huanxing Su
Zhong Pei
Ruxun Huang
author_sort Xingyong Chen
collection DOAJ
description Hypertension is associated with low-grade inflammation, and Toll-like receptor 4 (TLR4) has been shown to be linked to the development and maintenance of hypertension. This study aimed to investigate the effects of scutellarin (administered by oral gavage daily for 2 weeks) on brain TLR4/nuclear factor kappa B-(NF-κB-) mediated inflammation and blood pressure in renovascular hypertensive (using the 2-kidney, 2-clip method) rats. Immunofluorescence and western immunoblot analyses revealed that hypertension contributed to the activation of TLR4 and NF-κB, accompanied by significantly enhanced expression of proinflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-18 (IL-18). Furthermore, expression of the antiapoptotic protein, myeloid cell leukemia-1 (Mcl1), was decreased, and the pro-apoptotic proteins, Bax and cleavedcaspase-3 p17 were increased in combined cerebral cortical/striatal soluble lysates. Scutellarin significantly lowered blood pressure and attenuated the number of activated microglia and macrophages in brains of hypertensive rats. Furthermore, scutellarin significantly reduced the expression of TLR4, NF-κB p65, TNF-α, IL-1β, IL-18, Bax and cleaved-caspase-3 p17, and increased the expression of Mcl1. Overall, these results revealed that scutellarin exhibits anti-inflammatory and anti-apoptotic properties and decreases blood pressure in hypertensive rats. Therefore, scutellarin may be a potential therapeutic agent in hypertension-associated diseases.
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spelling doaj-art-b1b25fa85bdf4e0d95e37b8a581b43a62025-02-03T06:05:55ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/432623432623Scutellarin Attenuates Hypertension-Induced Expression of Brain Toll-Like Receptor 4/Nuclear Factor Kappa BXingyong Chen0Xiaogeng Shi1Xu Zhang2Huixin Lei3Simei Long4Huanxing Su5Zhong Pei6Ruxun Huang7Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Neurology, The Second Affiliated Hospital, Guangzhou University of Chinese Medicine, Guangzhou 510120, ChinaDepartment of Neurology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, ChinaDepartment of Neurology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, ChinaDepartment of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou 510080, ChinaKey Laboratory of Quality Research in Chinese Medicine, Institute of Chinese Medical Sciences, University of Macau, Taipa 999078, MacauDepartment of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou 510080, ChinaDepartment of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou 510080, ChinaHypertension is associated with low-grade inflammation, and Toll-like receptor 4 (TLR4) has been shown to be linked to the development and maintenance of hypertension. This study aimed to investigate the effects of scutellarin (administered by oral gavage daily for 2 weeks) on brain TLR4/nuclear factor kappa B-(NF-κB-) mediated inflammation and blood pressure in renovascular hypertensive (using the 2-kidney, 2-clip method) rats. Immunofluorescence and western immunoblot analyses revealed that hypertension contributed to the activation of TLR4 and NF-κB, accompanied by significantly enhanced expression of proinflammatory mediators, such as tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-18 (IL-18). Furthermore, expression of the antiapoptotic protein, myeloid cell leukemia-1 (Mcl1), was decreased, and the pro-apoptotic proteins, Bax and cleavedcaspase-3 p17 were increased in combined cerebral cortical/striatal soluble lysates. Scutellarin significantly lowered blood pressure and attenuated the number of activated microglia and macrophages in brains of hypertensive rats. Furthermore, scutellarin significantly reduced the expression of TLR4, NF-κB p65, TNF-α, IL-1β, IL-18, Bax and cleaved-caspase-3 p17, and increased the expression of Mcl1. Overall, these results revealed that scutellarin exhibits anti-inflammatory and anti-apoptotic properties and decreases blood pressure in hypertensive rats. Therefore, scutellarin may be a potential therapeutic agent in hypertension-associated diseases.http://dx.doi.org/10.1155/2013/432623
spellingShingle Xingyong Chen
Xiaogeng Shi
Xu Zhang
Huixin Lei
Simei Long
Huanxing Su
Zhong Pei
Ruxun Huang
Scutellarin Attenuates Hypertension-Induced Expression of Brain Toll-Like Receptor 4/Nuclear Factor Kappa B
Mediators of Inflammation
title Scutellarin Attenuates Hypertension-Induced Expression of Brain Toll-Like Receptor 4/Nuclear Factor Kappa B
title_full Scutellarin Attenuates Hypertension-Induced Expression of Brain Toll-Like Receptor 4/Nuclear Factor Kappa B
title_fullStr Scutellarin Attenuates Hypertension-Induced Expression of Brain Toll-Like Receptor 4/Nuclear Factor Kappa B
title_full_unstemmed Scutellarin Attenuates Hypertension-Induced Expression of Brain Toll-Like Receptor 4/Nuclear Factor Kappa B
title_short Scutellarin Attenuates Hypertension-Induced Expression of Brain Toll-Like Receptor 4/Nuclear Factor Kappa B
title_sort scutellarin attenuates hypertension induced expression of brain toll like receptor 4 nuclear factor kappa b
url http://dx.doi.org/10.1155/2013/432623
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