Stimulatory effect of icariin on the proliferation of neural stem cells from rat hippocampus

Abstract

BackgroundIcariin (ICA), a major ingredient of Epimediumbrevicornum, has various pharmacological activities including central nervous system protective functions such as the improvement of learning and memory function in mice models of Alzheimer’s disease. It has been reported that ICA can promote regeneration of peripheral nerve and functional recovery. The purpose of this study was to investigate the potentiating effect of ICA on the proliferation of rat hippocampal neural stem cells, and explore the possible mechanism involved.MethodsPrimary neural stem cells were prepared from the hippocampus of newly born SD rats, and cells were cultured in special stem cell culture medium. Neural stem cells were confirmed by immunofluorescence detection of nestin, NSE and GFAP expression. The effect of ICA on the growth and proliferation of the neural stem cells was evaluated by 5-ethynyl-2-deoxyuridine (EdU) labeling of proliferating cells, and photomicrographic images of the cultured neural stem cells. Further, the mechanism of ICA-induced cell proliferation of neural stem cells was investigated by analyzing the gene and protein expression of cell cycle related genes cyclin D1 and p21.ResultsThe present study showed that icariin promotes the growth and proliferation of neural stem cells from rat hippocampus in a dose-dependent manner. Incubation of cells with icariin resulted in significant increase in the number of stem cell spheres as well as the increased incorporation of EdU when compared with cells exposed to control vehicle. In addition, it was found that icariin-induced effect on neural stem cells is associated with increased mRNA and protein expression of cell cycle genes cyclin D1 and p21.ConclusionsThis study evidently demonstrates the potentiating effect of ICA on neural stem cell growth and proliferation, which might be mediated through regulation of cell cycle gene and protein expression promoting cell cycle progression.Electronic supplementary materialThe online version of this article (10.1186/s12906-018-2095-y) contains supplementary material, which is available to authorized users.

Troxerutin flavonoid has neuroprotective properties and increases neurite outgrowth and migration of neural stem cells from the subventricular zone

“…We performed proliferation assay as previously reported that flavonoids enhance the proliferation of NSCs in an in vitro cultures [15,16]. The results of clonogenic assay revealed that in the absence of growth factors, NSCs failed to proliferate and died on the 7 th day in all tested concentrations except in Control+ve supplemented with growth factors where cells rapidly proliferated to form neurospheres at all observation time points (Fig 3).…”

“…The self-renewal capacity and the differentiation into multiple cell types of the nervous system are characteristic features which make NSCs a very useful bio-tool for the screening of molecules which exert supporting effects on neural cell proliferation [15,16,55], differentiation [19,20,22], migration [23] and synaptogenesis [45]. Flavonoids serve as effective agents which provide antioxidative protection and neuroprotection.…”

“…Interestingly, plant-based molecules, especially flavonoids, modulate the fate of NSCs favourably as confirmed by several in vitro culture systems. Enhanced proliferation of NSCs from multiple niches was observed when exposed to epimedium flavonoids [15], icariin [16,17] and morin hydrate [18] whilst baicalin [19,20], apigenin [21] and quercetin have proven their efficacy in inducing neuronal differentiation of NSCs [22]. Quercetin-3-o-glucuronide was reported to promote the cell migration of NSCs of mouse hippocampus [23].…”

The Effects of Icariin on Enhancing Motor Recovery Through Attenuating Pro-inflammatory Factors and Oxidative Stress via Mitochondrial Apoptotic Pathway in the Mice Model of Spinal Cord Injury

“…Icariin has a neuroprotective effect in both acute and chronic central nervous system disease ( Fu et al, 2018 ). In our research, it demonstrated that ICA especially at a high dose promoted motor recovery after SCI.…”

Icariin as a new potential drug in Alzheimer disease treatment – a review

“…Another of the neuroprotective effects of ICA is to protect neurons from the harmful effects of hyperhomocysteinaemia [18]. In addition, there are reports that Icariin improves neurogenesis and the proliferation of neuronal stem cells in the hippocampus [3,19]. It is surprising is that ICA can improve memory function by stimulating NO/ cGMP signaling and the induction of nitric oxide synthase (NOS) isoforms [20].…”