Translational Medicine Center, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
Department of Spine Surgery, Honghui Hospital, Xi'an Jiaotong University, Xi'an, China.
Cell Biol Int. 2021 Dec;45(12):2429-2442. doi: 10.1002/cbin.11687. Epub 2021 Aug 23.
Compelling evidences suggest that transplantation of bone marrow-derived mesenchymal stem cells (BM-MSCs) can be therapeutically effective for central nervous system (CNS) injuries and neurodegenerative diseases. The therapeutic effect of BM-MSCs mainly attributes to their differentiation into neuron-like cells which replace injured and degenerative neurons. Importantly, the neurotrophic factors released from BM-MSCs can also rescue injured and degenerative neurons, which plays a biologically pivotal role in enhancing neuroregeneration and neurological functional recovery. Tetramethylpyrazine (TMP), the main bioactive ingredient extracted from the traditional Chinese medicinal herb Chuanxiong, has been reported to promote the neuronal differentiation of BM-MSCs. This study aimed to investigate whether TMP regulates the release of neurotrophic factors from BM-MSCs. We examined the effect of TMP on brain-derived neurotrophic factor (BDNF) released from BM-MSCs and elucidated the underlying molecular mechanism. Our results demonstrated that TMP at concentrations of lower than 200 μM increased the release of BDNF in a dose-dependent manner. Furthermore, the effect of TMP on increasing the release of BDNF from BM-MSCs was blocked by inhibiting the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (AKT)/cAMP-response element binding protein (CREB) pathway. Therefore, we concluded that TMP could induce the release of BDNF from BM-MSCs through activation of the PI3K/AKT/CREB pathway, leading to the formation of neuroprotective and proneurogenic microenvironment. These findings suggest that TMP possesses novel therapeutic potential to promote neuroprotection and neurogenesis through improving the neurotrophic ability of BM-MSCs, which provides a promising nutritional prevention and treatment strategy for CNS injuries and neurodegenerative diseases via the transplantation of TMP-treated BM-MSCs.
有强有力的证据表明，骨髓间充质干细胞（BM-MSCs）的移植对于中枢神经系统（CNS）损伤和神经退行性疾病具有治疗效果。BM-MSCs 的治疗效果主要归因于其分化为神经元样细胞，从而替代受损和变性的神经元。重要的是，BM-MSCs 释放的神经营养因子也可以挽救受损和变性的神经元，这在增强神经再生和神经功能恢复方面发挥了重要的生物学作用。川芎嗪（TMP）是从传统中药川芎中提取的主要生物活性成分，已被报道可促进 BM-MSCs 的神经元分化。本研究旨在探讨 TMP 是否调节 BM-MSCs 释放神经营养因子。我们研究了 TMP 对 BM-MSCs 释放脑源性神经营养因子（BDNF）的影响，并阐明了其潜在的分子机制。结果表明，TMP 在低于 200μM 的浓度下以剂量依赖性方式增加 BDNF 的释放。此外，PI3K/蛋白激酶 B（AKT）/cAMP 反应元件结合蛋白（CREB）通路的抑制阻断了 TMP 对 BM-MSCs 中 BDNF 释放的影响。因此，我们得出结论，TMP 通过激活 PI3K/AKT/CREB 通路诱导 BM-MSCs 释放 BDNF，从而形成神经保护和神经发生的微环境。这些发现表明，TMP 通过提高 BM-MSCs 的神经营养能力来促进神经保护和神经发生，从而为通过移植 TMP 处理的 BM-MSCs 治疗 CNS 损伤和神经退行性疾病提供了一种有前途的营养预防和治疗策略。
