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 factor kappa B-(NF- κ B-) 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- κ B, accompanied by significantly enhanced expression of proinflammatory mediators, such as tumor necrosis factor- α (TNF- α ), interleukin-1 β (IL-1 β ), 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- κ B p65, TNF- α , IL-1 β , 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.
Department of Neurology, National Key Clinical Department and Key Discipline of Neurology, The First Affiliated Hospital Sun Yat-Sen University, Guangzhou 510080, China ; Department of Neurology, Fujian Provincial Hospital, Fujian Medical University, Fuzhou 350001, China ; Guangdong Key Laboratory for Diagnosis and Treatment of Major Neurological Diseases, The First Affiliated Hospital, Sun Yat-Sen University, Guangzhou 510080, China.
Xingyong
X
Chen
Xiaogeng
X
Shi
Xu
X
Zhang
Huixin
H
Lei
Simei
S
Long
Huanxing
H
Su
Zhong
Z
Pei
Ruxun
R
Huang
D000818:Animals; D047310:Apigenin / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D005965:Glucuronates / Q000494:pharmacology*; D006973:Hypertension / Q000378:metabolism* / Q000503:physiopathology; D020382:Interleukin-18 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D017628:Microglia / Q000473:pathology; D064549:Myeloid Cell Leukemia Sequence 1 Protein / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051197:Toll-Like Receptor 4 / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
C494828:Bax protein, rat; D005965:Glucuronates; D020382:Interleukin-18; D053583:Interleukin-1beta; C579093:Mcl1 protein, rat; D064549:Myeloid Cell Leukemia Sequence 1 Protein; D016328:NF-kappa B; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; C484876:scutellarin; D047310:Apigenin; C505410:Casp3 protein, rat; D053148:Caspase 3