신경전구세포의 증식과 분화에 미치는 α-asarone의 영향
Effects of α-asarone on Proliferation and Differentiation of Neural Progenitor Cells
0
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
노인성 인지장애 등에 사용되어져 온 석창포 (Acorus gramineus Solander)의 뿌리줄기에 존재하는 주요 성분중 하나가 α-asarone이다. 본 연구는 신경전구세포와 해마조직절편배양을 이용하여 α-asarone이 신경전구세포의 증식과 분화에 미치는 영향을 살펴보았다. 신경전구세포와 해마조직에서의 증식과 분화 정도는 cell counting kit-8 분석과 증식과 분화의 바이오마크를 이용한 면역세포조직화학적 염색으로 확인하였다. 신경전구세포에 α-asarone을 처리하였을 때 특히 3 μM에서 현저한 세포증식을 보였다. 분화 정도를 보면 nestin과 함께 별아교세포와 희소돌기아교세포의 분화마크인 GFAP와 PDGFR-α 이 일부 관찰되었으나 신경세포의 분화마크인 Dcx의 발현이 가장 현저하였다. 배양한 해마조직절편에 α-asarone을처리했을 때 해마의 치아이랑에서 현저한 BrdU 및 Ki67 양성세포가 유의성 있게 증가하여 세포증식을 보였다. 이는특히 30 μM/ml 농도에서 가장 높게 나타났으며 새로이 형성 분화된 신경모세포인 BrdU/Dcx 이중양성세포의 증가도 현저하였다. α-asarone은 신경전구세포와 해마조직절편배양에서 현저한 신경전구세포의 증식과 분화를 촉진하는 것을 알 수있으며, 이는 뇌병변 질환에 대한 신경전구세포의 활성 치료에 대한 약물로서 가능성을 보여 준다.
Abstract
This study investigated whether α-asarone could promote proliferation and differentiation of neural progenitor cells into the neuronal cell types in in vitro and ex vivo studies. For in vitro assay, neural progenitor cells were isolated from fetal cerebral cortex (E15) and checked cell proliferation rate and neural progenitor cell marker in neurospheres. Treatment of α-asarone, particularly at a concentration of 3 μM, promoted the proliferation of neural progenitor cells and effectively differentiated neural progenitor cells into neurons. For ex vivo assay, a hippocampi slice culture system from 7 day postnatal rat fetuses was used. Although slight tissue damage was observed in the hippocampus after the high concentration (100 μM) of α-asarone, however, α-asarone enhanced the proliferation of neural progenitor cells in dentate gyrus region and also effectively differentiated into neuroblast at concentration of 30 μM. Consequently, α-asarone promotes the proliferation of neural progenitor cells and effectively differentiates neural progenitor cells into neurons. Therefore, our results support the therapeutic benefits of α-asarone for treating neurodegenerative diseases.
참고문헌 (34)
- Geraerts M, "Concise review: therapeutic strategies for Parkinson disease based on the modulation of adult neurogenesis", Stem Cells, 25, pp.263~270 (2007)[DOI]
- Volkman R, "Concise Review: Mesenchymal stem cells in neurodegenerative diseases", Stem Cells, 35, pp.1867~1880 (2017)[DOI]
- Gage FH, "Mammalian neural stem cells", Science, 287, pp.1433~1438 (2000)[DOI]
- Arvidsson A, "Neuronal replacement from endogenous precursors in the adult brain after stroke", Nat Med, 8, pp.963~970 (2002)[DOI]
- Parent JM, "Rat forebrain neurogenesis and striatal neuron replacement after focal stroke", Ann Neurol, 52, pp.802~813 (2002)[DOI]
- Poulose SM, "Nutritional factors affecting adult neurogenesis and cognitive function", Adv Nutr, 8, pp.804~811 (2017)[DOI]
- Han W, "Anti-arthritic effects of clematichinenoside (AR-6) on PI3K", Akt signaling pathway and TNF-alpha associated with collagen-induced arthritis, 2013, pp.51, 13~22
- Rajput SB, "An overview on traditional uses and pharmacological profile of Acorus calamus Linn. (Sweet flag) and other Acorus species", Phytomedicine, 21, pp.268~276 (2014)[DOI]
- Li M, "Antidepressant effect of water decoction of Rhizoma acori tatarinowii in the behavioural despair animal models of depression", Zhong Yao Cai, 24, pp.40~41 (2001)
- Zhang H, "Ameliorating effects of essential oil from Acori graminei rhizoma on learning and memory in aged rats and mice", J Pharm Pharmacol, 59, pp.301~309 (2007)[DOI]
- Jiang J, "Acorus gramineus inhibits microglia mediated neuroinflammation and prevents neurotoxicity in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of Parkinson's disease", J Ethnopharmacol, 144, pp.506~513 (2012)[DOI]
- Limon ID, "Neuroprotective effect of alpha-asarone on spatial memory and nitric oxide levels in rats injected with amyloid-beta (25-35)", Neurosci Lett, 453, pp.98~103 (2009)[DOI]
- Ma Y, "The effect of acori graminei rhizoma and extract fractions on spatial memory and hippocampal neurogenesis in amyloid beta 1-42 injected mice", CNS Neurol Disord Drug Targets, 14, pp.411~420 (2015)[DOI]
- Manikandan S, "Antioxidant property of alpha-asarone against noise-stress-induced changes in different regions of rat brain", Pharmacol Res, 52, pp.467~474 (2005)[DOI]
- Fang YQ, "Pharmacokinetics of beta-asarone in rabbit blood, hippocampus, cortex, brain stem, thalamus and cerebellum", Pharmazie, 67, pp.120~123 (2012)
- Pak ME, "Studies on medicinal herbs for cognitive enhancement based on the text mining of Dongeuibogam and preliminary evaluation of its effects", J Ethnopharmacol, 179, pp.383~390 (2016)[DOI]
- Lam KY, "Asarone from Acori Tatarinowii Rhizoma Potentiates the Nerve Growth Factor-Induced Neuronal Differentiation in Cultured PC12 Cells: A Signaling Mediated by Protein Kinase A", PLoS One, 11, pp.e0163337~ (2016)[DOI]
- Chellian R, "Pharmacology and toxicology of alpha- and beta-Asarone: A review of preclinical evidence", Phytomedicine, 32, pp.41~58 (2017)[DOI]
- Mao J, "A herbal medicine for Alzheimer's disease and its active constituents promote neural progenitor proliferation", Aging Cell, 14, pp.784~796 (2015)[DOI]
- Huang C, "alpha-asarone from Acorus gramineus alleviates epilepsy by modulating A-type GABA receptors", Neuropharmacology, 65, pp.1~11 (2013)[DOI]
- Kumar H, "Cognitive enhancing effects of alpha asarone in amnesic mice by influencing cholinergic and antioxidant defense mechanisms", Biosci Biotechnol Biochem, 76, pp.1518~1522 (2012)[DOI]
- Erlandsson A, "Immunosuppression promotes endogenous neural stem and progenitor cell migration and tissue regeneration after ischemic injury", Exp Neurol, 230, pp.48~57 (2011)[DOI]
- Kolb B, "Growth factor-stimulated generation of new cortical tissue and functional recovery after stroke damage to the motor cortex of rats", J Cereb Blood Flow Metab, 27, pp.983~997 (2007)[DOI]
- Donovan MH, "Decreased adult hippocampal neurogenesis in the PDAPP mouse model of Alzheimer's disease", J Comp Neurol, 495, pp.70~83 (2006)[DOI]
- Drapeau E, "Stem cell review series: role of neurogenesis in age-related memory disorders", Aging Cell, 7, pp.569~589 (2008)[DOI]
- Haughey NJ, "Disruption of neurogenesis by amyloid beta-peptide, and perturbed neural progenitor cell homeostasis, in models of Alzheimer's disease", J Neurochem, 83, pp.1509~1524 (2002)[DOI]
- Lie DC, "Neurogenesis in the adult brain: new strategies for central nervous system diseases", Annu Rev Pharmacol Toxicol, 44, pp.399~421 (2004)[DOI]
- Prager I, "Dose-dependent short- and long-term effects of ionizing irradiation on neural stem cells in murine hippocampal tissue cultures: neuroprotective potential of resveratrol", Brain Behav, 6, pp.e00548~ (2016)[DOI]
- Wang X, "Rescue of brain function using tunneling nanotubes between neural stem cells and brain microvascular endothelial cells", Mol Neurobiol, 53, pp.2480~2488 (2016)[DOI]
- Ziemka-Nalecz M, "Oxygen-glucose deprivation promotes gliogenesis and microglia activation in organotypic hippocampal slice culture: involvement of metalloproteinases", Acta Neurobiol Exp (Wars), 73, pp.130~142 (2013)
- Buchs PA, "Structural modifications associated with synaptic development in area CA1 of rat hippocampal organotypic cultures", Brain Res Dev Brain Res, 71, pp.81~91 (1993)[DOI]
- Mellentin C, "Properties of longterm synaptic plasticity and metaplasticity in organotypic slice cultures of rat hippocampus", Exp Brain Res, 170, pp.522~531 (2006)[DOI]
- Stoppini L, "A simple method for organotypic cultures of nervous tissue", J Neurosci Methods, 37, pp.173~182 (1991)[DOI]
- Zhao Y, "Gu Ling Pian, a traditional Chinese medicine, regulates function and OPG", RANKL synthesis of osteoblasts via the p38 MAPK pathway, 2007, pp.59, 1167~1173