Yang Yanqin, Wang Wenwen, Xiong Zhewen, Kong Jiamin, Wang Li, Qiu Yuwen, Shen Feihai, Huang Zhiying
Pharmazie. 2016 Sep 1;71(9):514-523. doi: 10.1691/ph.2016.6597.
Clinical application of triptolide (TP), a main active ingredient of the traditional Chinese herb Tripterygium wilfordii Hook f. (TWHF), is limited by a series of severe toxicities, including cardiotoxicity. In previous studies, we found the activation of sirtuin 3 (SIRT3) attenuated TP-induced toxicity in cardiomyocytes. Resveratrol (RSV), a polyphenol from the skins of grapes and red wine, is an activator of SIRT3. The current study aimed to investigate the protective effect of RSV against TP-induced cardiotoxicity and the underlying mechanisms. Mice were treated with a single dose of TP (2.5 mg/kg) via the intragastric (i.g.) route. After 24 h, TP induced abnormal changes of serum biochemistry, activity decrease of antioxidant enzymes and damage of heart tissue such as myocardial fiber rupture, cell swelling and interstitial congestion. In contrast, administration with RSV (50 mg/kg i.g. 12 h before and 2 h after the administration of TP) attenuated the detrimental effects induced by TP in BALB/c mice. Moreover, the cardiomyocyte protective effects of RSV on TP-induced heart injury were associated with the activation of SIRT3 and its downstream targets. In vitro study also indicated that RSV counteracted TP-induced cardiotoxicity through SIRT3-FOXO3 signaling pathway in H9c2 cells. Collectively, these findings suggest the potential of RSV as a promising agent in protecting heart from TP-induced damage.
雷公藤甲素（TP）是传统中药雷公藤（Tripterygium wilfordii Hook f., TWHF）的主要活性成分，其临床应用受到包括心脏毒性在内的一系列严重毒性的限制。在先前的研究中，我们发现沉默调节蛋白3（SIRT3）的激活可减轻TP诱导的心肌细胞毒性。白藜芦醇（RSV）是一种来自葡萄皮和红酒的多酚，是SIRT3的激活剂。本研究旨在探讨RSV对TP诱导的心脏毒性的保护作用及其潜在机制。小鼠通过灌胃（i.g.）途径接受单剂量TP（2.5 mg/kg）治疗。24小时后，TP诱导血清生化指标异常变化、抗氧化酶活性降低以及心脏组织损伤，如心肌纤维断裂、细胞肿胀和间质充血。相比之下，给予RSV（在TP给药前12小时和给药后2小时，50 mg/kg灌胃）可减轻TP对BALB/c小鼠诱导的有害影响。此外，RSV对TP诱导的心脏损伤的心肌细胞保护作用与SIRT3及其下游靶点的激活有关。体外研究还表明，RSV通过H9c2细胞中的SIRT3-FOXO3信号通路抵消TP诱导的心脏毒性。总的来说，这些发现表明RSV作为一种有前景的药物，在保护心脏免受TP诱导的损伤方面具有潜力。
