Pseudoginsenoside-F11 (PF11), an ocotillol-type ginsenoside, has been reported to exert neuroprotective effects on ischemic stroke induced by permanent and transient middle cerebral artery occlusion in experimental animals. The aim of the present study was to investigate the effect of PF11 on thromboembolic stroke in rats and its possible mechanisms on thromboinflammation. PF11 (4, 12, 36 mg/kg) was injected intravenously (i.v.) once a day for 3 consecutive days to male Wistar rats followed by embolic middle cerebral artery occlusion (eMCAO). The results showed that PF11 significantly reduced the cerebral infarction volume, brain edema and neurological deficits induced by eMCAO. Meanwhile, the thromboinflammation in the ischemic hemisphere was observed at 24 h after eMCAO, as indicated by the increased number of microvascular thrombus and inflammatory response. Moreover, eMCAO resulted in the up-regulation of platelet glycoprotein Ibα (GPIbα) and VI (GPVI), as well as the activation of contact-kinin pathway. Notably, PF11 significantly reversed all these changes. Furthermore, PF11 prevented the eMCAO-induced loss of tight junction proteins and up-regulation of matrix metalloproteinase-9 (MMP-9), thus leading to the alleviation of blood-brain barrier (BBB) damage. In conclusion, the present study revealed that thromboinflammation was induced in the ischemic hemisphere of rats after eMCAO and PF11 exerted marked protective effects against thromboembolic stroke by attenuating thromboinflammation and preventing BBB damage. This research further identifies the potential therapeutic role of PF11 for ischemic stroke.

Pseudoginsenoside-F11 (PF11) 是一种 ocotillol 型人参皂甙，据报道对实验动物永久性和短暂性大脑中动脉闭塞引起的缺血性卒中发挥神经保护作用。本研究旨在探讨PF11对大鼠血栓栓塞性卒中的影响及其对血栓炎症的可能机制。PF11 (4, 12, 36 mg/kg) 每天一次静脉内 (iv) 注射给雄性 Wistar 大鼠，连续 3 天，随后栓塞大脑中动脉闭塞 (eMCAO)。结果表明，PF11显着减少了eMCAO引起的脑梗死体积、脑水肿和神经功能缺损。同时，在 eMCAO 后 24 h 观察到缺血半球的血栓炎症，正如微血管血栓和炎症反应数量增加所表明的那样。此外，eMCAO 导致血小板糖蛋白 Ibα (GPIbα) 和 VI (GPVI) 的上调，以及接触激肽通路的激活。值得注意的是，PF11 显着逆转了所有这些变化。此外，PF11 可防止 eMCAO 诱导的紧密连接蛋白丢失和基质金属蛋白酶 9 (MMP-9) 的上调，从而减轻血脑屏障 (BBB) 损伤。总之，本研究表明，eMCAO 和 PF11 通过减轻血栓性炎症和防止 BBB 损伤对血栓栓塞性中风发挥显着的保护作用，从而在大鼠缺血性半球诱导血栓炎症。这项研究进一步确定了 PF11 对缺血性中风的潜在治疗作用。