Baicalein attenuates cardiac hypertrophy in mice via suppressing oxidative stress and activating autophagy in cardiomyocytes
Baicalein attenuates cardiac hypertrophy in mice via suppressing oxidative stress and activating autophagy in cardiomyocytes
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黄芩素通过抑制氧化应激和激活心肌细胞自噬来减轻小鼠心脏肥大
DOI：
10.1038/s41401-020-0496-1
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发表时间：
2020-08-14
影响因子：
8.2
通讯作者：
Wang, Jian-xun
中科院分区：
文献类型：
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作者：
Liu, Bing-yan;Li, Ling;Wang, Jian-xun
黄芩素是从黄芩根中提取的天然黄酮类化合物，具有多种药理活性。在这项研究中，我们研究了黄芩素在体内和体外对心脏肥大的保护作用的分子机制。通过注射异丙肾上腺素（ISO，30mg中心点kg(-1)中心点d(-1)）15天诱导小鼠心脏肥大。第3、6、9、12、15天尾静脉注射黄芩素(25 mg/kg)。我们发现，黄芩素给药可显着减轻 ISO 诱导的心脏肥大并恢复心脏功能。在用 ISO (10 μM) 处理的新生大鼠心肌细胞中也观察到黄芩素对心脏肥大的保护作用。在心肌细胞中，ISO 处理显着增加活性氧 (ROS) 并抑制自噬，而黄芩素 (30 μM) 预处理可大大缓解这种情况。我们发现黄芩素预处理增加了过氧化氢酶和线粒体自噬受体 FUN14 结构域 1 (FUNDC1) 的表达，从而清除 ROS 并促进自噬，从而减弱 ISO 诱导的心脏肥大。此外，我们发现黄芩素直接与转录因子FOXO3a结合，促进其转录活性，并反式激活过氧化氢酶和FUNDC1。总之，我们的数据为黄芩素和 FOXO3a 调节 ISO 诱导的心脏肥大提供了新的证据。黄芩素在治疗心脏肥大方面具有巨大潜力。
Baicalein is a natural flavonoid extracted from the root ofScutellaria baicalensisthat exhibits a variety of pharmacological activities. In this study, we investigated the molecular mechanisms underlying the protective effect of baicalein against cardiac hypertrophy in vivo and in vitro. Cardiac hypertrophy was induced in mice by injection of isoproterenol (ISO, 30 mg center dot kg(-1)center dot d(-1)) for 15 days. The mice received caudal vein injection of baicalein (25 mg/kg) on 3rd, 6th, 9th, 12th, and 15th days. We showed that baicalein administration significantly attenuated ISO-induced cardiac hypertrophy and restored cardiac function. The protective effect of baicalein against cardiac hypertrophy was also observed in neonatal rat cardiomyocytes treated with ISO (10 mu M). In cardiomyocytes, ISO treatment markedly increased reactive oxygen species (ROS) and inhibited autophagy, which were greatly alleviated by pretreatment with baicalein (30 mu M). We found that baicalein pretreatment increased the expression of catalase and the mitophagy receptor FUN14 domain containing 1 (FUNDC1) to clear ROS and promote autophagy, thus attenuated ISO-induced cardiac hypertrophy. Furthermore, we revealed that baicalein bound to the transcription factor FOXO3a directly, promoting its transcription activity, and transactivated catalase and FUNDC1. In summary, our data provide new evidence for baicalein and FOXO3a in the regulation of ISO-induced cardiac hypertrophy. Baicalein has great potential for the treatment of cardiac hypertrophy.