Key Laboratory of Bioactive Substances and Resources Utilization of Chinese Herbal Medicine (Ministry of Education), Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences & Peking Union Medical College, No. 151 Malianwa North Road, Haidian District, Beijing 100193, China.
Institute of Drug Discovery Technology, Ningbo University, No. 818 Fenghua Road, Ningbo 315211, China.
Molecules. 2023 Aug 3;28(15):5837. doi: 10.3390/molecules28155837.
Myelin repair, which is known as remyelination, is critical to the treatment of neurodegenerative diseases, and myelination depends on not only the differentiation of oligodendrocyte precursor cells toward oligodendrocytes but also the renewal of oligodendrocyte precursor cells under pathological conditions. However, simultaneously promoting the differentiation and proliferation of oligodendrocyte precursor cells in lesions remains an unmet challenge and might affect demyelinating diseases. Kidney-tonifying herbs of traditional Chinese medicine (TCM) are effective in improving the symptoms of degenerative patients. However, herbs or compounds with dual functions are unverified. The purpose of this study was to find a kidney-tonifying TCM that synchronously improved the differentiation and proliferation of oligodendrocyte precursor cells under pathological conditions. Compounds with dual functions were screened from highly frequently used kidney-tonifying TCM, and the effects of the obtained compound on remyelination were investigated in an in vitro oligodendrocyte precursor cell differentiation model under pathological conditions and in demyelinating mice in vivo. The compound icaritin, which is an active component of Yin-Yang-Huo (the leaves of Maxim), demonstrated multiple effects on the remyelination process, including enhancing oligodendrocyte precursor cell proliferation, facilitating the differentiation of neural progenitor cells toward oligodendrocyte precursor cells and further toward oligodendrocytes, and maturation of oligodendrocytes under corticosterone- or glutamate-induced pathological conditions. Importantly, icaritin effectively rescued behavioral functions and increased the formation of myelin in a cuprizone-induced demyelination mouse model. The multiple effects of icaritin make it a promising lead compound for remyelination therapy.
髓鞘修复，即再髓鞘化，对神经退行性疾病的治疗至关重要，而髓鞘的形成不仅依赖于少突胶质前体细胞向少突胶质细胞的分化，还依赖于病理条件下少突胶质前体细胞的更新。然而，同时促进病变中少突胶质前体细胞的分化和增殖仍然是一个未满足的挑战，可能会影响脱髓鞘疾病。补肾中药对改善退行性患者的症状有一定效果。然而，具有双重功能的草药或化合物尚未得到验证。本研究旨在寻找一种补肾中药，使其能同步改善病理条件下少突胶质前体细胞的分化和增殖。从常用补肾中药中筛选出具有双重功能的化合物，并在病理条件下体外少突胶质前体细胞分化模型和体内脱髓鞘小鼠中研究所得化合物对髓鞘再生的影响。淫羊藿（ Maxim 的叶子）中的活性成分淫羊藿苷对髓鞘再生过程具有多种作用，包括增强少突胶质前体细胞增殖、促进神经祖细胞向少突胶质前体细胞分化，进一步向少突胶质细胞分化，以及在皮质酮或谷氨酸诱导的病理条件下促进少突胶质细胞成熟。重要的是，淫羊藿苷能有效改善行为功能，增加杯状霉素诱导的脱髓鞘小鼠模型中髓鞘的形成。淫羊藿苷的多种作用使其成为髓鞘再生治疗的有前途的先导化合物。
