Differentiation Effect of Two Alkaloid Fractions from Vietnamese Lycopodiaceae on Mouse Neural Stem Cells
DOI:
https://doi.org/10.18006/2022.10(1).64.72Keywords:
Lycopodium clavatum, Huperzia serrata, Lycopodium Alkaloid, Neuronal Disease, Mouse Neural Stem CellAbstract
Various Lycopodium alkaloids have been studied for their various biological activities including anti-inflammatory, antioxidant, immunomodulatory, and neuroprotective activities. Moreover, these alkaloid compounds have high potential in the treatment of neuron degenerative disease. This study has been carried out to test the effect of Huperzia serrata (Thunb.) Trevis, and Lycopodium clavatum L alkaloid fractions on the mouse neural stem cells (NSCs). Firstly, the alkaloid fractions were used to verify its toxicity on NSCs. The multiple concentrations of alkaloid fractions from H. serrata (0.044; 0.088; 0.175; 0.35; 0.7; 1.4 mg/ml) and L. clavatum (0.031; 0.063; 0.125; 0.25; 0.50; 1.0; 2.0 mg/ml) have been used for the treatment of NSCs at period of 48h incubation. Results of the study suggested that the IC50 value of H. serrata and L. clavatum was 0.56 mg/ml and 0.50 mg/ml, respectively. Then, the NSCs were differentiated in the presence of 5 and 10 µg/ml of alkaloid fraction from H. serrata; 0.625 and 1.25 µg/ml of alkaloid fraction from L. clavatum for 6 days. Here, we observed the primary NSCs treated with alkaloid fraction extract from H. serrata showed the increased gene expression level of early neuron TUBB3 and neuron-specific cytoskeleton MAP2. On the other hand, the L. clavatum alkaloid fraction increased the expression of neural stem cell marker genes (Nestin and PAX6) and decreased neuron marker genes. In conclusion, these results established that alkaloid fraction from H. serrata promoted differentiation of the mouse NSCs to neuron cells, and L. clavatum extract had a capacity for stemness maintenance.
References
Ayer, W.A. (1991). The lycopodium alkaloids. Natural Product Reports 8(5), 455-63. https://doi.org/10.1039/NP9910800455. DOI: https://doi.org/10.1039/np9910800455
Calderón, A.I., Simithy-Williams, J., Sanchez, R., Espinosa, A., Valdespino, I., & Gupta, M.P. (2013). Lycopodiaceae from Panama: a new source of acetylcholinesterase inhibitors. Natutal Product Research, 27(4-5), 500-505. https://doi.org/10.1080/ 14786419.2012.701217. DOI: https://doi.org/10.1080/14786419.2012.701217
Chuong, N.N., Huong, N.T., Hung, T.M., & Luan, T.C. (2014). Anti-cholinesterase activity of lycopodium alkaloids from Vietnamese Huperzia squarrosa (Forst.) Trevis. Molecules, 19(11), 19172-9. https://doi.org/10.3390/molecules191119172. DOI: https://doi.org/10.3390/molecules191119172
Dymek, A., Widelski, J., Wojtanowski, K.K., Vivcharenko, V., Przekora, A., & Mroczek, T. (2021). Fractionation of lycopodiaceae alkaloids and evaluation of their anticholinesterase and cytotoxic activities. Molecules, 26(21), 6379. doi: 10.3390/molecules26216379. DOI: https://doi.org/10.3390/molecules26216379
Friedli, M.J., & Inestrosa, N.C. (2021). Huperzine A and its neuroprotective molecular signaling in Alzheimer’s Disease. Molecules, 26(21), 6531. https://doi.org/10.3390/molecules26216531. DOI: https://doi.org/10.3390/molecules26216531
Fujita, S. (2003). The discovery of the matrix cell, the identification of the multipotent neural stem cell, and the development of the central nervous system. Cell Structure and Function, 28(4), 205-28. https://doi.org/10.1247/csf.28.205. DOI: https://doi.org/10.1247/csf.28.205
Gage, F.H. (2000). Mammalian neural stem cells. Science, 287(5457), 1433-1438. https://doi.org/10.1126/science.287.5457.1433. DOI: https://doi.org/10.1126/science.287.5457.1433
Giang, V.H., Thuy, L.T., Hanh, T.T.H., Cuong, N.X., et al. (2022). Cytotoxic and nitric oxide inhibitory activities of triterpenoids from Lycopodium clavatum L. Natural Product Research 6:1-8. doi: 10.1080/14786419.2021.2024824. DOI: https://doi.org/10.1080/14786419.2021.2024824
Hanif, K., Kumar, M., Singh, N., & Shukla, R. (2015). Effect of homeopathic Lycopodium clavatum on memory functions and cerebral blood flow in memory-impaired rats. Homeopathy, 104(1), 24-28. https://doi.org/10.1016/j.homp.2014.08.003. DOI: https://doi.org/10.1016/j.homp.2014.08.003
Jalal, F.Y. (2019). Lycopodium attenuates loss of dopaminergic neurons by suppressing oxidative stress and neuroinflammation in a rat model of Parkinson’s Disease. Molecules, 24(11), 2182. https://doi.org/10.3390/molecules24112182. DOI: https://doi.org/10.3390/molecules24112182
Kitajima, M., & Takayama, H. (2011). Lycopodium alkaloids: isolation and asymmetric synthesis. Alkaloid synthesis, 309, 1-31. https://doi.org/10.1007/128_2011_126. DOI: https://doi.org/10.1007/128_2011_126
Li, J., Meng, X., Li, F., Liu, J., Ma, M., & Chen, W. (2021). Huperzine A combined with hyperbaric oxygen on the effect on cognitive function and serum hypoxia-inducible factor-1α Level in elderly patients with vascular dementia. American Journal of Translational Research, 13(6), 6897-6904.
Livak, K.J., & Schmittgen, T.D. (2001). Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) Method. Methods, 25(4), 402-408. https://doi.org/10.1006/meth.2001.1262. DOI: https://doi.org/10.1006/meth.2001.1262
Ma, T., Gong, K., Yan, Y., Zhang, L., et al. (2013) Huperzine A promotes hippocampal neurogenesis in vitro and in vivo. Brain Research, 1506, 35-43. https://doi.org/10.1016/ j.brainres.2013.02.026. DOI: https://doi.org/10.1016/j.brainres.2013.02.026
Ma, X., & Gang, D.R. (2004). The Lycopodium alkaloids. Natural Product Reports, 21(6), 752-72. https://doi.org/10.1039/B409720N. DOI: https://doi.org/10.1039/b409720n
Nakatomi, H., Kuriu, T., Okabe, S., Yamamoto, S., et al. (2002) Regeneration of hippocampal pyramidal neurons after ischemic brain injury by recruitment of endogenous neural progenitors. Cell, 110(4), 429-41. https://doi.org/10.1016/S0092-8674(02)00862-0. DOI: https://doi.org/10.1016/S0092-8674(02)00862-0
Noctor, S.C., Flint, A.C., Weissman, T.A., Dammerman, R.S., & Kriegstein, A.R. (2001). Neurons derived from radial glial cells establish radial units in neocortex. Nature, 409(6821), 714-720. https://doi.org/10.1038/35055553. DOI: https://doi.org/10.1038/35055553
Orhan, I., Terzioglu, S., & Sener, B. (2003). Alpha-onocerin: an acetylcholinesterase inhibitor from Lycopodium clavatum. Planta Medica, 69(3), 265-267. https://doi.org/10.1055/s-2003-38489. DOI: https://doi.org/10.1055/s-2003-38489
Russo, I., Barlati, S., & Bosetti, F. (2011). Effects of neuroinflammation on the regenerative capacity of brain stem cells. Journal of Neurochemistry, 116(6), 947-956. https://doi.org/10.1111/j.1471-4159.2010.07168.x. DOI: https://doi.org/10.1111/j.1471-4159.2010.07168.x
Siengalewicz, P., Mulzer, J., & Rinner, U. (2013). Lycopodium alkaloids synthetic highlights and recent developments. The Alkaloids Chemistry and Biology, 72, 1-151. https://doi.org/10.1016/B978-0-12-407774-4.00001-7. DOI: https://doi.org/10.1016/B978-0-12-407774-4.00001-7
Takouda, J., Katada, S., & Nakashima, K. (2017). Emerging mechanisms underlying astrogenesis in the developing mammalian brain. Proceedings of Japan Academy, Series B, 93(6), 386-398. https://doi.org/10.2183/pjab.93.024. DOI: https://doi.org/10.2183/pjab.93.024
Temple, S. (2001). The development of neural stem cells. Nature, 414(6859), 112-117. https://doi.org/10.1038/35102174. DOI: https://doi.org/10.1038/35102174
Thu, D.K., Vui, D.T., & Tung, B.T. (2019). Two Lycopodium Alkaloids from the aerial parts of Huperzia phlegmaria. Pharmacognosy Research, 11(4), 396-399. http://dx.doi.org/10.4103/pr.pr_82_19. DOI: https://doi.org/10.4103/pr.pr_82_19
Wang, C.Y., Zheng, W., Wang, T., Xie, J.W., et al. (2011). Huperzine A activates Wnt/β-catenin signaling and enhances the
nonamyloidogenic pathway in an Alzheimer transgenic mouse model. Neuropsychopharmacology, 36(5), 1073-1089. https://doi.org/10.1038/npp.2010.245. DOI: https://doi.org/10.1038/npp.2010.245
Wang, Z.F., & Tang, X.C. (2007). Huperzine A protects C6 rat glioma cells against oxygen-glucose deprivation-induced injury. FEBS Letters, 581(4), 596-602. https://doi.org/10.1016/j.febslet.2007.01.016. DOI: https://doi.org/10.1016/j.febslet.2007.01.016
Yang, G., Wang, Y., Tian, J., & Liu, J.P. (2013). Huperzine A for Alzheimer's disease: a systematic review and meta-analysis of randomized clinical trials. PLoS One, 8(9), e74916. https://doi.org/10.1371/journal.pone.0074916. DOI: https://doi.org/10.1371/journal.pone.0074916
Zangara, A. (2003). The psychopharmacology of huperzine A: an alkaloid with cognitive enhancing and neuroprotective properties of interest in the treatment of Alzheimer's disease. Pharmacology Biochemistry and Behavior, 75(3), 675-86. https://doi.org/10.1016/S0091-3057(03)00111-4. DOI: https://doi.org/10.1016/S0091-3057(03)00111-4
Zhang, H.Y., Yan, H., & Tang, X.C. (2008). Non-cholinergic effects of huperzine A: beyond inhibition of acetylcholinesterase. Cellular Molecular Neurobiology, 28(2), 173-83. https://doi.org/10.1007/s10571-007-9163-z. DOI: https://doi.org/10.1007/s10571-007-9163-z
Zhu, N., Lin, J., Wang, K., Wei, M., Chen, Q., & Wang, Y. (2015). Huperzine A protects neural stem cells against Aβ-induced apoptosis in a neural stem cells and microglia co-culture system. International Journal of Clinical & Experimental Pathology, 8(6), 6425-33. PMC4525852.
Zhu, X., Yan, J., Bregere, C., Zelmer, A., et al. (2019). RBM3 promotes neurogenesis in a niche dependent manner via IMP2-IGF2 signaling pathway after hypoxic-ischemic brain injury. Nature Communications, 10, 3982. https://doi.org/10.1038/s41467-019-11870-x. DOI: https://doi.org/10.1038/s41467-019-11870-x
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