Gao Jiale, Liu Jianxun, Yao Mingjiang, Zhang Wei, Yang Bin, Wang Guangrui
Beijing Key Laboratory of Pharmacology of Chinese Materia Medica, Institute of Basic Medical Sciences of Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Department of Pathology, Xiyuan Hospital, China Academy of Chinese Medical Sciences, Beijing, China.
Front Pharmacol. 2022 Jun 13;13:889404. doi: 10.3389/fphar.2022.889404. eCollection 2022.
Saponins (PNS), the main active component of herbal medicine Panax notoginseng, has been widely used to treat cerebrovascular diseases. It has been acknowledged that PNS exerted protection on nerve injuries induced by ischemic stroke, however, the long-term impacts of PNS on the restoration of neurological defects and neuroregeneration after stroke have not been thoroughly studied and the underlying molecular mechanism of stimulating neurogenesis is difficult to precisely clarify, much more in-depth researches are badly needed. In the present study, cerebral ischemia injury was induced by microsphere embolism (ME) in rats. After 14 days, PNS administration relieved cerebral ischemia injury as evidenced by alleviating neurological deficits and reducing hippocampal pathological damage. What's more, PNS stimulated hippocampal neurogenesis by promoting cell proliferation, migration and differentiation activity and modulated synaptic plasticity. Increased number of BrdU/Nestin, BrdU/DCX and NeuroD1-positive cells and upregulated synapse-related GAP43, SYP, and PSD95 expression were observed in the hippocampus. We hypothesized that upregulation of brain-derived neurotrophic factor (BDNF) expression and activation of Akt/mTOR/p70S6K signaling after ME could partially underlie the neuroprotective effects of PNS against cerebral ischemia injury. Our findings offer some new viewpoints into the beneficial roles of PNS against ischemic stroke.
皂苷（三七总皂苷，PNS）是中药三七的主要活性成分，已被广泛用于治疗脑血管疾病。人们已经认识到PNS对缺血性中风引起的神经损伤具有保护作用，然而，PNS对中风后神经功能缺损恢复和神经再生的长期影响尚未得到充分研究，刺激神经发生的潜在分子机制也难以精确阐明，因此急需进行更深入的研究。在本研究中，通过微球栓塞（ME）诱导大鼠脑缺血损伤。14天后，给予PNS可减轻脑缺血损伤，表现为神经功能缺损减轻和海马病理损伤减少。此外，PNS通过促进细胞增殖、迁移和分化活性刺激海马神经发生，并调节突触可塑性。在海马中观察到BrdU/Nestin、BrdU/DCX和NeuroD1阳性细胞数量增加，以及突触相关蛋白GAP43、SYP和PSD95表达上调。我们推测，ME后脑源性神经营养因子（BDNF）表达上调以及Akt/mTOR/p70S6K信号通路激活可能是PNS对脑缺血损伤神经保护作用的部分潜在机制。我们的研究结果为PNS对缺血性中风的有益作用提供了一些新观点。
