Endocannabinoids are well‐known regulators of neurotransmission by activating the cannabinoid (CB) receptors. Endocannabinoids are being used extensively for the treatment of various neurological disorders such as Alzheimer's and Parkinson's diseases. Although endocannabinoids are well studied in cell survival, proliferation, and differentiation in various neurological disorders and several cancers, the functional role in the regulation of blood cell development is less examined. In the present study, virodhamine, which is an agonist of CB receptor‐2, was used to examine its effect on megakaryocytic development from a megakaryoblastic cell. We observed that virodhamine increases cell adherence, cell size, and cytoplasmic protrusions. Interestingly, we have also observed large nucleus and increased expression of megakaryocytic marker (CD61), which are the typical hallmarks of megakaryocytic differentiation. Furthermore, the increased expression of CB2 receptor was noticed in virodhamine‐induced megakaryocytic cells. The effect of virodhamine on megakaryocytic differentiation could be mediated through CB2 receptor. Therefore, we have studied virodhamine induced molecular regulation of megakaryocytic differentiation; mitogen‐activated protein kinase (MAPK) activity, mitochondrial function, and reactive oxygen species (ROS) production were majorly affected. The altered mitochondrial functions and ROS production is the crucial event associated with megakaryocytic differentiation and maturation. In the present study, we report that virodhamine induces megakaryocytic differentiation by triggering MAPK signaling and ROS production either through MAPK effects on ROS‐generating enzymes or by the target vanilloid receptor 1‐mediated regulation of mitochondrial function.

中文翻译：

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Virodhamine 是一种内源性大麻素，通过调节 MAPK 活性和线粒体功能诱导巨核细胞分化。

内源性大麻素是众所周知的通过激活大麻素 (CB) 受体来调节神经传递的物质。内源性大麻素被广泛用于治疗各种神经系统疾病，如阿尔茨海默氏症和帕金森氏病。尽管内源性大麻素在各种神经系统疾病和几种癌症中的细胞存活、增殖和分化方面得到了很好的研究，但其在调节血细胞发育中的功能作用却鲜有研究。在本研究中，病毒罗丹明是 CB 受体 2 的激动剂，用于检查其对巨核细胞巨核细胞发育的影响。我们观察到病毒罗达明增加细胞粘附、细胞大小和细胞质突起。有趣的是，我们还观察到大细胞核和巨核细胞标志物（CD61）的表达增加，这是巨核细胞分化的典型标志。此外，在病毒罗丹明诱导的巨核细胞中观察到 CB2 受体的表达增加。病毒罗丹明对巨核细胞分化的影响可能是通过CB2受体介导的。因此，我们研究了病毒罗他明诱导的巨核细胞分化的分子调控；丝裂原活化蛋白激酶 (MAPK) 活性、线粒体功能和活性氧 (ROS) 产生受到主要影响。线粒体功能的改变和 ROS 的产生是与巨核细胞分化和成熟相关的关键事件。在目前的研究中，