多发性硬化是一种常见的中枢神经系统脱髓鞘性疾病,全世界分布范围极广,一直以来是神经疾病领域的研究热点。多发性硬化疾病通过慢性或急性的方式损害中枢神经系统的内在平衡,并能够促进大脑及脊髓大量神经细胞的凋亡,由于中枢神经系统自我修复能力有限,针对MS疾病的治疗带来了一定挑战。近年来,黄酮类中药提取物单体,如灯盏花乙素、黄岑苷、人参皂苷和黄芩素在多发性硬化疾病中的研究备受研究者的广泛关注,越来越多的单体被挖掘解析。本文综述了近年来黄酮类中药提取物单体在多发性硬化的相关研究应用进展。在具体阐明已有成果的基础上,分析了现阶段应用研究中面临的问题与挑战,并对未来多发性硬化中的研究趋势进行了展望。
Multiple sclerosis (MS) is a common demyelinating disease of central nervous system. It is widely distributed in the world, and has been a research hotspot in the field of neurological diseases. Mul-tiple sclerosis can damage the internal balance of the central nervous system in a chronic or acute way, and can promote the apoptosis of a large number of nerve cells in the brain and spinal cord. Due to the limited self-healing ability of the central nervous system, the treatment of MS disease poses certain challenges. In recent years, the research of flavonoid traditional Chinese medicine ex-tract monomers, such as scutellarin, breviscapine, ginsenoside and baicalein in multiple sclerosis disease has attracted extensive attention of researchers, and more and more monomers have been mined and analyzed. In this paper, the recent research progress of flavonoids in multiple sclerosis was reviewed. On the basis of expounding the existing achievements, the problems and challenges faced in the application research at this stage are analyzed, and the research trend of multiple scle-rosis in the future is prospected.
1Institute of Biomedical Engineering, Kunming Medical University, Kunming Yunnan
2Yunnan Provincial Key Laboratory of Stem Cell and Regenerative Medicine, Institute of Biomedical Engineering, Kunming Medical University, Kunming Yunnan
Multiple sclerosis (MS) is a common demyelinating disease of central nervous system. It is widely distributed in the world, and has been a research hotspot in the field of neurological diseases. Multiple sclerosis can damage the internal balance of the central nervous system in a chronic or acute way, and can promote the apoptosis of a large number of nerve cells in the brain and spinal cord. Due to the limited self-healing ability of the central nervous system, the treatment of MS disease poses certain challenges. In recent years, the research of flavonoid traditional Chinese medicine extract monomers, such as scutellarin, breviscapine, ginsenoside and baicalein in multiple sclerosis disease has attracted extensive attention of researchers, and more and more monomers have been mined and analyzed. In this paper, the recent research progress of flavonoids in multiple sclerosis was reviewed. On the basis of expounding the existing achievements, the problems and challenges faced in the application research at this stage are analyzed, and the research trend of multiple sclerosis in the future is prospected.
徐君铭,陈武龙,刘书阁,张林雁,王淑芬. 黄酮类中药提取物单体在多发性硬化中的研究进展Research Progress of Flavonoid Chinese Herbal Extract Monomers in Multiple Sclerosis[J]. 临床医学进展, 2022, 12(06): 5713-5719. https://doi.org/10.12677/ACM.2022.126825
参考文献ReferencesScolding, N.J., Pasquini, M., Reingold, S.C., et al. (2017) Cell-Based Therapeutic Strategies for Multiple Sclerosis. Brain, 140, 2776-2796. <br>https://doi.org/10.1093/brain/awx154Tandon, A., Singh, S.J. and Chaturvedi, R.K. (2018) Stem Cells as Potential Targets of Polyphenols in Multiple Sclerosis and Alzheimer’s Disease. BioMed Research International, 2018, Article ID: 1483791.
<br>https://doi.org/10.1155/2018/1483791Uccelli, A., Laroni, A., Brundin, L., et al. (2019) MEsenchymal StEm Cells for Multiple Sclerosis (MESEMS): A Randomized, Double Blind, Cross-Over Phase I/II Clinical Trial with Au-tologous Mesenchymal Stem Cells for the Therapy of Multiple Sclerosis. Trials, 20, Article No. 263. <br>https://doi.org/10.1186/s13063-019-3346-zCuascut, F.X. and Hutton, G.J. (2019) Stem Cell-Based Thera-pies for Multiple Sclerosis: Current Perspectives. Biomedicines, 7, Article No. 26. <br>https://doi.org/10.3390/biomedicines7020026Jafarzadeh Bejargafshe, M., Hedayati, M., Zahabiasli, S., Tah-masbpour, E., Rahmanzadeh, S. and Nejad-Moghaddam, A. (2019) Safety and Efficacy of Stem Cell Therapy for Treat-ment of Neural Damage in Patients with Multiple Sclerosis. Stem Cell Investigation, 6, 44. <br>https://doi.org/10.21037/sci.2019.10.06Tzeng, Y.M. and Lee, M.J. (2015) Neuroprotective Properties of Ka-valactones. Neural Regeneration Research, 10, 875-877. <br>https://doi.org/10.4103/1673-5374.158335Rajamani, K., Liu, J.W., Wu, C.H., Chiang, I.T., You, D.H., Lin, S.Y., Hsieh, D.K., Lin, S.Z., Harn, H.J. and Chiou, T.W. (2017) n-Butylidenephthalide Exhibits Protection against Neurotoxicity through Regulation of Tryptophan 2, 3 Dioxygenase in Spinocerebellar Ataxia Type 3. Neuropharmacology, 117, 434-446.
<br>https://doi.org/10.1016/j.neuropharm.2017.02.014Gao, Y.L., Zhang, Y., Cao, J.P., Wu, S.B., Cai, X.H., Zhang, Y.C., Zhang, R.J., Song, X.G. and Zhang, L.D. (2017) Regulation of the Endoplasmic Reticulum Stress Re-sponse and Neuroprotective Effects of Acupuncture on Brain Injury Caused by Heroin Addiction. Acupuncture in Medi-cine, 35, 366-373.
<br>https://doi.org/10.1136/acupmed-2016-011220Remondelli, P. and Renna, M. (2017) The Endoplasmic Retic-ulum Unfolded Protein Response in Neurodegenerative Disorders and Its Potential Therapeutic Significance. Frontiers in Molecular Neuroscience, 10, Article No. 187.
<br>https://doi.org/10.3389/fnmol.2017.00187Zhang, P.Y., Guo, T., He, H.Y., Yang, L.Q. and Deng, Y.H. (2017) Breviscapine Confers a Neuroprotective Efficacy against Transient Focal Cerebral Ischemia by Attenuating Neu-ronal and Astrocytic Autophagy in the Penumbra. Biomedicine & Pharmacotherapy, 90, 69-76. <br>https://doi.org/10.1016/j.biopha.2017.03.039Wang, W.W., Han, J.H., Wang, L. and Bao, T.H. (2017) Scu-tellarin May Alleviate Cognitive Deficits in a Mouse Model of Hypoxia by Promoting Proliferation and Neuronal Dif-ferentiation of Neural Stem Cells. Iranian Journal of Basic Medical Sciences, 20, 272-279.Chaparro, E., Quiroga, C., Erasso, D., Bosco, G., Rubini, A., Mangar, D., et al. (2014) Isoflurane Prevents Learning Deficiencies Caused by Brief Hypoxia and Hypotension in Adult Sprague Dawley Rats. Journal of Enzyme Inhibition and Medicinal Chemistry, 29, 895-900. <br>https://doi.org/10.3109/14756366.2013.866658Veazey, K.J., Carnahan, M.N., Muller, D., Mi-randa, R.C. and Golding, M.C. (2013) Alcohol-Induced Epigenetic Alterations to Developmentally Crucial Genes Regu-lating Neural Stemness and Differentiation. Alcoholism: Clinical and Experimental Research, 37, 1111-1122. <br>https://doi.org/10.1111/acer.12080Guo, X., Lian, R., Guo, Y., Liu, Q., Ji, Q. and Chen, J. (2015) bFGF and Activin A Function to Promote Survival and Proliferation of Single iPS Cells in Conditioned Half-Exchange mTeSR1 Medium. Human Cell, 28, 122-132.
<br>https://doi.org/10.1007/s13577-015-0113-7Wu, X.S., Bao, T.H., Ke, Y., Sun, D.Y., Shi, Z.T., Tang, H.R., et al. (2016) Hint1 Suppresses Migration and Invasion of Hepatocellular Carcinoma Cells in Vitro by Modulating Girdin Activity. Tumor Biology, 37, 14711-14719.
<br>https://doi.org/10.1007/s13277-016-5336-zZhuang, P.W., Cui, G.Z., Zhang, Y.J., et al. (2013) Baicalin Reg-ulates Neuronal Fate Decision in Neural Stem/Progenitor Cells and Stimulates Hippocampal Neurogenesis in Adult Rats. CNS Neuroscience & Therapeutics, 19, 154-162.
<br>https://doi.org/10.1111/cns.12050Quintard, H., Borsotto, M., Veyssiere, J., et al. (2011) MLC901, a Tradi-tional Chinese Medicine Protects the Brain against Global Ischemia. Neuropharmacology, 61, 622-631. <br>https://doi.org/10.1016/j.neuropharm.2011.05.003Zhuang, P., Zhang, Y., Cui, G., et al. (2012) Direct Stimu-lation of Adult Neural Stem/Progenitor Cells in Vitro and Neurogenesis in Vivo by Salvianolic Acid B. PLOS ONE, 7, e35636. <br>https://doi.org/10.1371/journal.pone.0035636Li, Y., Zhuang, P.W., Shen, B.G., Zhang, Y.J. and Shen, J.G. (2012) Baicalin Promotes Neuronal Differentiation of Neural Stem/Progenitor Cells through Modulating p-stat3 and bHLH Family Protein Expression. Brain Research, 1429, 36-42. <br>https://doi.org/10.1016/j.brainres.2011.10.030Bond, A.M., Bhalala, O.G. and Kessler, J.A. (2012) The Dy-namic Role of Bone Morphogenetic Proteins in Neural Stem Cell Fate and Maturation. Developmental Neurobiology, 72, 1068-1084. <br>https://doi.org/10.1002/dneu.22022Jang, E.S. and Goldman, J.E. (2011) Pax6 Expression Is Sufficient to Induce a Neurogenic Fate in Glial Progenitors of the Neonatal Subventricular Zone. PLOS ONE, 6, e20894. <br>https://doi.org/10.1371/journal.pone.0020894Han, S.H., Kim, S.J., Yun, Y.W., Nam, S.Y., Lee, H.J. and Lee, B.J. (2018) Protective Effects of Cultured and Fermented Ginseng Extracts against Scopolamine-Induced Memory Loss in a Mouse Model. Laboratory Animal Research, 34, 37-43. <br>https://doi.org/10.5625/lar.2018.34.1.37Wang, Z.L., Chen, L.B., Qiu, Z., et al. (2018) Ginsenoside Rg1 Ameliorates Testicular Senescence Changes in D-Gal-Induced Aging Mice via Anti-Inflammatory and Antioxidative Mechanisms. Molecular Medicine Reports, 17, 6269-6276. <br>https://doi.org/10.3892/mmr.2018.8659Sacco, R., Cacci, E. and Novarino, G. (2018) Neural Stem Cells in Neuropsychiatric Disorders. Current Opinion in Neurobiology, 48, 131-138. <br>https://doi.org/10.1016/j.conb.2017.12.005Zhao, L., Zhou, C., Li, L., et al. (2017) Acupuncture Improves Cerebral Microenvironment in Mice with Alzheimer’s Disease Treated with Hippocampal Neural Stem Cells. Molecular Neurobiology, 54, 5120-5130.
<br>https://doi.org/10.1007/s12035-016-0054-5Zhu, D., Liu, M., Yang, Y., et al. (2014) Ginsenoside Rd Ame-liorates Experimental Autoimmune Encephalomyelitis in C57BL/6 Mice. Journal of Neuroscience Research, 92, 1217-1226. <br>https://doi.org/10.1002/jnr.23397Jin, B., Zhang, C., Geng, Y., et al. (2020) Therapeutic Effect of Ginsenoside Rd on Experimental Autoimmune Encephalomyelitis Model Mice: Regulation of Inflammation and Treg/Th17 Cell Balance. Mediators of Inflammation, 2020, Article ID: 8827527. <br>https://doi.org/10.1155/2020/8827527Mirshafiey, A. and Jadidi-Niaragh, F. (2010) Immunopharmacological Role of the Leukotriene Receptor Antagonists and Inhibitors of Leukotrienes Generating Enzymes in Multiple Sclerosis. Immunopharmacology and Immunotoxicology, 32, 219-227. <br>https://doi.org/10.3109/08923970903283662Rong, S., Cao, Q., Liu, M., Seo, J., Jia, L., Boudyguina, E., et al. (2012) Macrophage 12/15 Lipoxygenase Expression Increases Plasma and Hepatic Lipid Levels and Exacerbates Atherosclerosis. Journal of Lipid Research, 53, 686-695.
<br>https://doi.org/10.1194/jlr.M022723Poulsen, L., Siersbaek, M. and Mandrup, S. (2012) PPARs: Fatty Acid Sensors Controlling Metabolism. Seminars in Cell & Developmental Biology, 23, 631-639. <br>https://doi.org/10.1016/j.semcdb.2012.01.003Xu, J., Zhang, Y., Xiao, Y., et al. (2013) Inhibition of 12/15-Lipoxygenase by Baicalein Induces Microglia PPARβ/δ: A Potential Therapeutic Role for CNS Autoimmune Dis-ease. Cell Death & Disease, 4, e569.
<br>https://doi.org/10.1038/cddis.2013.86Gray, E., Ginty, M., Kemp, K., Scolding, N. and Wilkins, A. (2012) The PPAR-Gamma Agonist Pioglitazone Protects Cortical Neurons from Inflammatory Mediators via Improvement in Peroxisomal Function. Journal of Neuroinflammation, 9, Article No. 63. <br>https://doi.org/10.1186/1742-2094-9-63