Wang Zhaojun, Liu Zhongqing, Hao Ying, Zhu Zhanchi, Hong Jing, Cui Leisha, Cheng Guosheng, Tan Rui
College of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China; School of Nano-Tech and Nano-Bionics, University of Science and Technology of China, Hefei 230026, China; CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
College of Life Science and Engineering, Southwest Jiaotong University, Chengdu 610031, China; CAS Key Laboratory of Nano-Bio Interface, Suzhou Institute of Nano-Tech and Nano Bionics, Chinese Academy of Sciences, Suzhou 215123, China.
Phytomedicine. 2025 Aug;144:156905. doi: 10.1016/j.phymed.2025.156905. Epub 2025 May 30.
Ischemic stroke induced irreversible damage or loss of neurons, severely causing high death rates. Natural medicine has rapidly risen for stroke therapy. Given the activation of neural cells, it is crucial to reveal the neuroregulation and molecular mechanisms of natural medicine for developing effective therapeutical approaches for stroke. Safflower is recommended widely in traditional Chinese medicine for the treatment of ischemic stroke. However, hydroxysafflor yellow A (HSYA) as a bioactive component of safflower underlying its neurogenic effects remains largely unknown.
We aimed to study the role and underlying mechanisms of HSYA in regulating neural stem cell (NSC) behaviors and endogenous neural regeneration after stroke.
CCK-8 assay was performed to detect cell viability. Immunofluorescent staining, RT-qPCR, and western blot were employed to verify the effects of HSYA on cell proliferation and differentiation of NSCs. Finally, the transient middle cerebral artery occlusion-reperfusion (MCAO/R) model, neurofunctional test, laser speckle imaging system, TTC staining, western blot and immunohistochemistry were used to investigate brain injury repair and endogenous neural regeneration in MACO/R rats treated with HSYA.
HSYA could noticeably promote the proliferation and differentiation of NSCs in vitro. Meanwhile, the therapeutic effect of HSYA on MCAO/R rats was evaluated using edaravone as a positive drug. The behavioral functions, infarcted volume, brain water content and apoptosis Nissl bodies of MCAO/R rats were significantly improved after HSYA treatment. Also, HSYA showed neuroprotective, endogenous neural regeneration, blood flow recanalization potential and motor function reconstruction in vivo, as evidenced by enhancement of the neurological function recovery, promotion of endogenous neurogenesis and astrogenesis, and increase of the cerebral blood flow.
HSYA could promote NSC proliferation and neuronal differentiation in vitro, and regulate endogenous neural regeneration post-stroke, providing a novel strategy for investigating the neural effects of natural medicine in stroke therapy. More importantly, the mechanism of HSYA on NSC proliferation and endogenous neurogenesis was revealed in this work.
缺血性中风会导致神经元不可逆的损伤或丧失，严重导致高死亡率。天然药物在中风治疗中迅速兴起。鉴于神经细胞的激活，揭示天然药物的神经调节和分子机制对于开发有效的中风治疗方法至关重要。红花在传统中医中被广泛推荐用于治疗缺血性中风。然而，羟基红花黄色素A（HSYA）作为红花的一种生物活性成分，其神经源性作用在很大程度上仍不清楚。
我们旨在研究HSYA在调节中风后神经干细胞（NSC）行为和内源性神经再生中的作用及潜在机制。
采用CCK-8法检测细胞活力。运用免疫荧光染色、RT-qPCR和蛋白质印迹法验证HSYA对NSC细胞增殖和分化的影响。最后，采用短暂性大脑中动脉闭塞再灌注（MCAO/R）模型、神经功能测试、激光散斑成像系统、TTC染色、蛋白质印迹法和免疫组织化学法研究HSYA治疗的MACO/R大鼠的脑损伤修复和内源性神经再生。
HSYA在体外能显著促进NSC的增殖和分化。同时，以依达拉奉作为阳性对照药物评估HSYA对MCAO/R大鼠的治疗效果。HSYA治疗后，MCAO/R大鼠的行为功能、梗死体积、脑含水量和凋亡尼氏体均有显著改善。此外，HSYA在体内显示出神经保护、内源性神经再生、血流再通潜力和运动功能重建，表现为神经功能恢复增强、内源性神经发生和星形胶质细胞生成增加以及脑血流量增加。
HSYA在体外可促进NSC增殖和神经元分化，并调节中风后的内源性神经再生，为研究天然药物在中风治疗中的神经作用提供了新策略。更重要 的是，本研究揭示了HSYA对NSC增殖和内源性神经发生的作用机制。
