Icariin improves cognitive deficits and activates quiescent neural stem cells in aging rats
ABSTRACT Icariin represents an important active component in Herba Epimedii, which is a famous Chinese herbal medicine that is widely used to treat some age-related diseases in oriental countries.
The aim of this work was to investigate the effects of icariin on cognitive function in natural aging rats, and then to explore its mechanism by investigating the activation of quiescent neural stem cells (NSCs) in the hippocampus.
Sprague-Dawley rats that were 18 months of age were divided into two groups including treated rats (i.e., icariin was administered from the age of 18 months to 21 months) and control rats (i.e., only saline was administered). The Morris water maze (MWM) tasks were then employed to measure spatial learning and memory. Subsequently, AraC was infused into the brain with osmotic minipumps in order to destroy proliferative stem cells primarily leaving quiescent NSCs. After seven days of recovery, 5-bromodeoxyuridine (BrdU) was co-labeled with markers for NSC to identify NSCs.
The results from the MWM indicated that icariin has a beneficial effect on cognitive function in aging rats. In addition, by double-labeling BrdU and glial fibrillary acidic protein (GFAP), our findings indicated that NSC activation is markedly increased in the icariin-treated rats compared to control rats. For example, a much greater increase was produced in BrdU and highly polysialylated neural cell adhesion molecule (PSA-NCAM) and BrdU and Olig2 double-labeled cells following icariin treatment.
Our findings suggest that icariin represents a promising candidate for the modulation of aging. Therefore, icariin administration may effectively prevent or delay the onset of age-related cognitive degeneration, and its capability to activate quiescent NSCs may potentially be one of its mechanisms.
[Show abstract] [Hide abstract]
ABSTRACT: The present study investigated the effects and potential mechanism(s) of action of icariin on the reproductive functions of male rats. Adult rats were treated orally with icariin at doses of 0 (control), 50, 100, or 200 mg/kg body weight for 35 consecutive days. The results show that icariin had virtually no effect on the body weight or organ coefficients of the testes or epididymides. However, 100 mg/kg icariin significantly increased epididymal sperm counts. In addition, 50 and 100 mg/kg icariin significantly increased testosterone levels. Real-time PCR suggests icariin may be involved in testosterone production via mRNA expression regulation of genes such as peripheral type benzodiazepine receptor (PBR) and steroidogenic acute regulatory protein (StAR). Furthermore, 100 mg/kg icariin treatment also affected follicle stimulating hormone receptor (FSHR) and claudin-11 mRNA expression in Sertoli cells. Superoxide dismutase (SOD) activity and malondialdehyde (MDA) levels were measured in the testes; 50 and 100 mg/kg icariin treatment improved antioxidative capacity, while 200 mg/kg icariin treatment upregulated oxidative stress. These results collectively suggest that icariin within a certain dose range is beneficial to male reproductive functions; meanwhile, higher doses of icariin may damage reproductive functions by increasing oxidative stress in the testes.Molecules 07/2014; 19(7):9502-9514. DOI:10.3390/molecules19079502 · 2.10 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Objective: The purpose of this study was to investigate the effects and pharmacological mechanisms of icariin, which is the main component in the traditional Chinese herb Epimedium, on β-amyloid (Aβ) production in an amyloid precursor protein (APP) transgenic (Tg) mouse model of Alzheimer's disease (AD). Methods: APPV717I Tg mice were randomly divided into a model group and icariin-treated (30 and 100 μmol/kg per day) groups. Learning-memory abilities were determined by Morris water maze and object recognition tests. Aβ contents were measured by enzyme-linked immunosorbent assays and immunohistochemistry. Amyloid plaques were detected by Congo red staining and Bielschowsky silver staining. The levels of expression of APP and β-site APP-cleaving enzyme 1 (BACE-1) were measured by western blotting and immunohistochemistry. Results: Ten-month-old Tg mice showed obvious learning-memory impairments, and significant increases in Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus. The intragastric administration of icariin to Tg mice for 6 months (from 4 to 10 months of age) improved the learning-memory abilities and significantly decreased the Aβ contents, amyloid plaques, and APP and BACE-1 levels in the hippocampus. Conclusion: Icariin reduced the Aβ burden and amyloid plaque deposition in the hippocampus of APP transgenic mice by decreasing the APP and BACE-1 levels. These novel findings suggest that icariin may be a promising treatment in patients with AD.International journal of biological sciences 01/2014; 10(2):181-91. DOI:10.7150/ijbs.6232 · 4.37 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: To investigate the effects and underlying molecular mechanisms of icariin (ICA) on self-renewal and differentiation of neural stem cells (NSCs). NSCs were derived from forebrains of mice embryos by mechanical dissociation into single cell suspension. The self-renewal of NSCs was measured by neurosphere formation assay. The proliferation of NSCs was detected by water-soluble tetrazolium (WST) and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assay. Protein expression of neuron-specific marker tubulin-βIII(TuJ1) and astrocyte-specific marker glial fibrillary acidic protein (GFAP) were measured by immunofluorescence and Western blotting. Using microarray, the differentially expressed genes (DEGs) were screened between NSCs with or without ICA treatment. The signaling pathways enriched by these DEGs and their role in mediating effects of ICA were analyzed. ICA significantly promoted neurosphere formation of NSCs cultured in growth protocol in a dose-dependent manner and achieved the maximum effects at 100 nmol/L. ICA also increased optical absorbance value and EdU incorporation into nuclei of NSCs. ICA had no significant effects on the percentage of TuJ1 or GFAP-positive cells, and TuJ1 or GFAP protein expression in NSCs cultured in differentiation protocol. A total of 478 genes were found to be differentially regulated. Among signaling pathways significantly enriched by DEGs, mitogen activated protein kinase (MAPK) pathway was of interest. Blockade of extracellular signal-regulated kinase (ERK)/MAPK, other than p38/MAPK subfamily pathway partially abolished effects of ICA on neurosphere formation and EdU incorporation of NSCs. ICA can promote the selfrenewal of NSCs at least partially through ERK/MAPK signaling pathway.Chinese Journal of Integrative Medicine 02/2014; 20(2):107-15. DOI:10.1007/s11655-013-1583-7 · 1.40 Impact Factor