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.

中文翻译：

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Tetramethylpyrazine 通过激活 PI3K/AKT/CREB ​​通路诱导 BM-MSC 释放 BDNF


令人信服的证据表明，骨髓间充质干细胞（BM-MSC）移植可有效治疗中枢神经系统（CNS）损伤和神经退行性疾病。 BM-MSCs的治疗效果主要归因于它们分化为神经元样细胞，替代受损和退化的神经元。重要的是，BM-MSC释放的神经营养因子还可以拯救受损和退化的神经元，这在增强神经再生和神经功能恢复方面发挥着生物学上的关键作用。四甲基吡嗪（TMP）是从传统中药川芎中提取的主要生物活性成分，据报道可以促进 BM-MSCs 的神经元分化。本研究旨在探讨 TMP 是否调节 BM-MSC 释放神经营养因子。我们检查了 TMP 对 BM-MSC 释放的脑源性神经营养因子 (BDNF) 的影响，并阐明了潜在的分子机制。我们的结果表明，浓度低于 200 μM 的 TMP 以剂量依赖性方式增加 BDNF 的释放。此外，通过抑制磷脂酰肌醇-4,5-二磷酸3-激酶（PI3K）/蛋白激酶B（AKT）/cAMP反应元件结合蛋白（CREB），TMP增加BM-MSCs释放BDNF的作用被阻断。 ）途径。因此，我们得出结论，TMP可以通过激活PI3K/AKT/CREB途径诱导BM-MSCs释放BDNF，从而形成神经保护性和促神经源性微环境。 这些发现表明，TMP具有通过提高BM-MSC的神经营养能力来促进神经保护和神经发生的新治疗潜力，这为通过TMP处理的BM-MSC移植来预防和治疗中枢神经系统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。