Cryptotanshinone possesses therapeutic effects on ischaemic stroke through regulating STAT5 in a rat model

Cryptotanshinone (CT), a lipophilic compound extracted from roots of Salvia miltiorrhiza Bunge (Lamiaceae) (Danshen), has multiple properties in diseases, such as pulmonary fibrosis, lung cancer, and osteoarthritis. Our previous findings suggest that CT plays a protective role in cerebral stroke. However, the molecular mechanisms underlying CT protection in ischaemic stroke remain unclear.
This study examines the effect of CT on ischaemic stroke.
We used the middle cerebral artery occlusion (MCAO) rat (Sprague-Dawley rats, 200 ± 20 g, n = 5) model with a sham operation group was treated as negative control. MCAO rats were treated with 15 mg/kg CT using intragastric administration. Moreover, TGF-β (5 ng/mL) was used to treat MCAO rats as a positive control group.
The 50% inhibitory concentration (IC50) of CT on CD4+ cell damage was 485.1 μg/mL, and median effective concentration (EC50) was 485.1 μg/mL. CT attenuates the infarct region in the MCAO model. The percentage of CD4+CD25+FOXP3+ Treg cells in the peripheral blood of the MCAO group was increased with CT treatment. The protein level of FOXP3 and the phosphorylation of STAT5 were recovered in the CD4+CD25+ Treg cells of model group after treated with CT. Importantly, the effects of CT treatment were blocked by treatment with the inhibitor STAT5-IN-1 in CD4+ T cells of the MCAO model.
Our findings not only enhance the understanding of the mechanisms underlying CT treatment, but also indicate its potential value as a promising agent in the treatment of ischaemic stroke. Further study will be valuable to examine the effects of CT on patients with ischaemic stroke.

隐丹参酮（Cryptotanshinone, CT）是从唇形科（Lamiaceae）植物丹参（Salvia miltiorrhiza Bunge）根部提取的脂溶性化合物，在肺纤维化、肺癌、骨关节炎等多种疾病中展现出多样的药理活性。既往研究表明，CT对脑卒中具有保护作用，但CT在缺血性脑卒中中发挥保护作用的分子机制仍未阐明。
本研究旨在探究CT对缺血性脑卒中的干预作用。
本研究采用大脑中动脉闭塞（middle cerebral artery occlusion, MCAO）大鼠模型（Sprague-Dawley大鼠，体重200±20g，n=5），并设置假手术组作为阴性对照。通过灌胃给药方式向MCAO模型大鼠给予15mg/kg的CT。此外，以5ng/mL的转化生长因子-β（transforming growth factor-β, TGF-β）处理MCAO大鼠，以此作为阳性对照组。
CT对CD4+细胞损伤的半数抑制浓度（50% inhibitory concentration, IC50）为485.1μg/mL，半数有效浓度（median effective concentration, EC50）同样为485.1μg/mL。CT可缩小MCAO模型大鼠的脑梗死区域。经CT处理后，MCAO模型大鼠外周血中CD4+CD25+FOXP3+调节性T细胞（Treg细胞）的占比显著升高。在模型组大鼠的CD4+CD25+Treg细胞中，FOXP3的蛋白表达水平以及信号转导与转录激活因子5（STAT5）的磷酸化水平均得到恢复。值得注意的是，在MCAO模型的CD4+T细胞中，CT的治疗效应可被STAT5抑制剂STAT5-IN-1所阻断。
本研究结果不仅加深了我们对CT治疗缺血性脑卒中分子机制的理解，同时也提示其作为缺血性脑卒中潜在治疗药物的应用价值。后续开展CT用于缺血性脑卒中患者的相关研究将具有重要意义。