细胞凋亡
免疫印迹
血管紧张素II
药理学
化学
无限冲激响应
医学
内分泌学
生物化学
血压
数字滤波器
滤波器(信号处理)
计算机科学
计算机视觉
基因
作者
Yuan Lin,Chi-Yi Lin,Hsien Tsung Yao,Wei Wen Kuo,Chia Yao Shen,Yu Lan Yeh,Tsung Jung Ho,V. Vijaya Padma,Yu Chen Lin,Chih Yang Huang
标识
DOI:10.1016/j.jep.2017.04.028
摘要
Platycodon grandiflorum (PG) is a Chinese medical plant used for decades as a traditional prescription to eliminate phlegm, relieve cough, reduce inflammation and lower blood pressure. PG also has a significant effect on the cardiovascular systems. The aqueous extract of Platycodon grandiflorum (JACQ.) A. DC. root was screened for inhibiting Ang II-induced IGF-IIR activation and apoptosis pathway in H9c2 cardiomyocytes. The effects were also studied in spontaneously hypertensive rats (five groups, n=5) using low and high doses of PG for 50 days. The Ang II-induced IGF-IIR activation was analyzed by luciferase reporter, RT-PCR, western blot and surface IGF-IIR expression assay. Furthermore, the major active constituent of PG was carried out by high performance liquid chromatography-mass spectrometry (HPLC-MS). Our results indicate that a crude extract of PG significantly suppresses the Ang II-induced IGF-IIR signaling pathway to prevent cardiomyocyte apoptosis. PG extract inhibits Ang II-mediated JNK activation and SIRT1 degradation to reduce IGF-IIR activity. Moreover, PG maintains SIRT1 stability to enhance HSF1-mediated IGF-IIR suppression, which prevents cardiomyocyte apoptosis. In animal models, the administration of PG markedly reduced this apoptotic pathway in the heart of SHRs. Taken together, PG may be considered as an effective treatment for cardiac diseases in hypertensive patients.
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