The study of the effect of quercetin on the proliferation and differentiation of neural stem cells of sub-ventricular zone (SVZ) in the adult rats
Subject Areas :Ali Ebrahimi 1 , Kazem Parivar 2 , nasim hayati roodbari 3 , Akram Eidi 4
1 - Department of Biology, Faculty of Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
2 - Department of Animal Biology, Faculty of Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
3 - Department of Biology, Faculty of Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
4 - Department of Biology, Faculty of Science, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Keywords: Proliferation, Quercetin, Sub-Ventricular Zone (SVZ), Differentiation,
Abstract :
The presence of neural precursor stem cells (NSCs) in some parts of the adult brains and the potency of these types of cells for the acceleration of the proliferation and differentiation processes with a therapeutic viewpoint is another beneficial facet of the application of neural precursor stem cells in cell biology. Quercetin, as an herbal flavonoid, has been extensively investigated and shown to have numerous effects on some cell-lines and disorders. We aimed to investigate the impact of quercetin, on proliferation and differentiation of NSCs derived from the subventricular zone (SVZ) of the adult rat brains. The isolated SVZs were mechanically minced into pieces through repeated pipetting in phosphate-buffered saline, incubated with 0.25% trypsin and treated with trypsin inhibitor; then centrifuged to obtain the cell suspension. The obtained cell suspension was cultured for one week to achieve neurospheres. When the cells reached confluence of 70-80%, they were sub-cultured for three passages and in the third passage, quercetin was treated with the cultured cells at the concentrations of 1, 5, and 15 μM. Methods such as Real time-PCR, MTT assay and ImageJ software, have been used to validate differentiation and proliferation of cells. The results indicated that the differentiation rate of NSCs is affected by various concentrations of quercetin in a dose-dependent manner so that 1µM quercetin had the least, and 15µM quercetin showed the most effects on cell differentiation. However, 1µM quercetin exhibited no significant cell toxicity, the most antiproliferative potential showed when treated with 15µM concentration quercetin.
1.Ademosun, A.O., Oboh, G., Bello, F., Ayeni, P.O. (2015). Antioxidative properties and effect of quercetin and its glycosylated form (Rutin) on acetylcholinesterase and but yryl cholinesterase activities, J. Evid. Based Complementary Altern. Med. 4 (2015), doi:http://dx.doi.org/10. 1177/2156587215610032.
2.Allison, M., Bond, M., Hongjun, S. (2015). Adult mammalian neural stem cells and neurogenesis: five decades later. Cell Stem Cell, 17(4); 385–395.
3.Alrawaiq, N.S., Abdullah, A. (2014). A review of flavonoid quercetin: metabolism:bioactivity and antioxidant properties. Int.J. PharmTech Res, 6; 933–941.
4.Ambron, RT., Walters, ET. (1996). Priming events and retrograde injurysignals. A new perspective on the cellular and molecular biology of nerve regeneration, [J]. Mol Neurobiol, 13(2); 61-79.
5.Boots, AW., Haenen, GR., Bast, A. (2008). Health effects of quercetin: from antioxidant to nutraceutical. [J]. Eur J Pharmacol, 585(2-3); 325-337.
6.Bischoff, SC. (2008). Quercetin: potentials in the prevention and therapy of disease. [J]. Curr Opin Clin Nutr Metab Care, 11(6); 733-740.
7.Chen, M., Yin. Z., Zhang, L., Liao, H.(2015). Quercetin promotes neurite growth through enhancing intracellular cAMP level and GAP-43 expression. Chinese Journal of Natural Medicines, 13(9); 0667-0672 .
8.Chen, ZL., Yu, WM., Sidney, S. (2007). Peripheral regeneration. [J]. Annu Rev Neurosci, 30; 209-233.
9.Cho, JY., Kim, IS., Jang, YH. (2006). Protective effect of quercetin, a natural flavonoid against neuronal damage after transient global cerebral ischemia. [J]. Neurosci Lett, 404(3); 330-335.
10.Dajas, F., Rivera-Megret, F., Blasina, F. (2003). Neuroprotection by flavonoids, [J]. Braz J Med Biol Res, 36(12); 1613-1620.
11.Golmohammadi, MG., Sagha, M., Azari, H., Najafzadeh, N. (2011). Isolation of neural stem and progenitor cells from the adult mouse brainusing the neurosphere assay. Journal of Ardabil Univ Med Sci, 11(3); 246-258.
12.Guillermo Gormaz J., S. Quintremil, R. (2015). Cardiovascular disease a target for the pharmacological effects of quercetin. Curr. Topics Med. Chem.,15;1735–1742.
13.Ilary, A., Esther, U., Xavier, N. (2012). Specificity of peripheral nerve regeneration: Interactions at the axon level. [J]. Prog Neurobiol. (2); 98- 106.
14.Johari, J., Kianmehr, A., Mustafa, M.R., Abubakar, S., Zandi, K. (2012). Antiviral activity of baicalein and quercetin against the Japanese encephalitis virus. Int. J. Mol. Sci.,13; 16785–16795.
15.Nakajima, K.I., Niisato, N., Marunaka, Y. (2011). Quercetin stimulates NGF-induced neurite outgrowth in PC12 cells via activation of Na+/K+/2Cl-cotransporter. Cell. Physiol. Biochem., 28;147–156.
16.Namiko, A., Valeria, C. (2008).Nerve injury signaling. [J]. Curr Opin Neurobiol, 18(30);276-283.
17.Natarajan, S., Pandima, D. K., Nabavi, Se. F. (2011). Bioactive effects of quercetin in the central nervous system: Focusing on the mechanisms of actions. Journal of Ardabil Univ Med. Sci, 11(3); 246-258.
18.Ohnishi, H., Sato, M., Ohnishi-Kameyama, M., Matsunaga, I., Naito, S. (2015). Estimated daily intake and seasonal food sources of quercetin in Japan. Nutrients, 7; 2345–2358.
19.Palazzolo, G., Horvath, P., Zenobi-Wong, M. (2012). The flavonoid isoquercitrin promotes neurite elongation by reducing RhoA activity. PLoS One, 7;e49979.
20.Robaszkiewicz, A., Balcerczyk, A., Bartosz, G. (2007). Antioxidative and prooxidative effects of quercetin on A549 cells. Cell. Biol. Int., 31; 1245–1250.
21.Russo, M., Spagnuolo, C., Tedesco, I., Bilotto, S., Russo, G.L. (2012). The flavonoid quercetin in disease prevention and therapy: facts and fancies. Biochem. Pharmacol, 83; 6–15.
22.Schültke, E., Kamencic, H., Zhao, M. (2005). Neuroprotection following fluid percussion brain trauma: a pilot study using quercetin. [J]. J Neurotrauma, 22(12); 1475-1484.
23.Sharma, V., Mishra, M., Ghosh, S., Tewari, R., Basu, A., Seth, P. (2007). Modulation of interleukin-1b mediated inflammatory response in human astrocytes by flavonoids: implications in neuroprotection. Brain Res. Bull, 73; 55–63.
24.Shu-Ting, Ch. (2014). Oral and intraperitoneal administration of quercetin decreased lymphocyte DNA damage and plasma lipid peroxidation induced by TSA in vivo. BioMed Research International, 1155(10); 2133-2143.
25.Sun ,G.Y., Chen, Z., Jasmer, K.J., Chuang, D.Y., Gu, Z., Hannink, M. (2015). Quercetin attenuates inflammatory responses in BV-2 microglial cells: role of MAPKs on the nrf2 pathway and induction of heme oxygenase-1. PLoS One, 10;e0141509.
26.Taupin, P. (2011). Neurogenesis, NSCs, pathogenesis and therapies for lzheimer's disease. Front Biosci., (Schol Ed) 3; 178-190.
27.Testa, G., Gamba, P., Badilli, U., Gargiulo, S., Maina, M., Guina, T. (2014). Loading into nanoparticles improves quercetin's efficacy in preventing neuroinflammation induced by oxysterols. PLoS. One., 9;e96795.
28.Yue, L., Zhen-Gang, T., Yi, L., Xin-Guo, Qu., Wei, L., Guo-Bin, Wang, C. (2017). Effects of quercetin on proliferation and migration of human glioblastoma U251 cells. Biomedicine & Pharmacotherapy, 92;33–38.
29.Zhang, M., Swarts, S.G., Yin, L., Liu, C., Tian, Y., Cao, Y. (2011). Antioxidant properties of quercetin oxygen transport to tissue XXXII. Springer, 283–289
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