Scutellarin attenuates hypertension-induced expression of brain Toll-like receptor 4/nuclear factor kappa B.

Xingyong Chen,Zhong Pei,Ruxun Huang,Huanxing Su,Simei Long,Xu Zhang,Huixin Lei,Xiaogeng Shi

doi:10.1155/2013/432623

Abstract

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.

Highlights

Hypertension is a major risk factor for cardiovascular accidents [1] and may accelerate the onset and progression of ischemia stroke and cerebral hemorrhage [2]
Toll-like receptors (TLRs) are first-line molecules for initiating the innate immune responses, and its signaling is involved in the activation of microglia by pathogens and damaged host cells
To investigate the potential effect of scutellarin on neuronal cell survival, we evaluated the expression of the apoptosis-related proteins, myeloid cell leukemia-1 (Mcl1), Bax, and cleavedcaspase-3 p17 in brains of hypertensive and sham-operated rats

Summary

Introduction

Hypertension is a major risk factor for cardiovascular accidents [1] and may accelerate the onset and progression of ischemia stroke and cerebral hemorrhage [2]. Hypertension is associated with low-grade inflammation, which may be associated with hypertension-mediated damage to target organs [3]. Inflammation in brain parenchyma can occur as a local process that can be triggered and sustained by activated glial cells, which is thought to contribute to the pathogenesis of several diseases [3]. The innate immune response, predominantly represented by Toll-like receptors (TLRs), has been shown to contribute to the development of this condition [4]. TLRs are first-line molecules for initiating the innate immune responses, and its signaling is involved in the activation of microglia by pathogens and damaged host cells. Activated microglia subsequently secret proinflammatory cytokines and express costimulatory molecules needed for protective immune responses to pathogens and efficient clearance of damaged tissues [6]

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