Icariin improves cognitive deficits and activates quiescent neural stem cells in aging rats

Institute of Integrative Chinese and Western Medicine, Huashan Hospital, Fudan University, No. 12, Wu Lu Mu Qi (Middle) Road, Shanghai 200040, PR China.
Journal of ethnopharmacology (Impact Factor: 3). 06/2012; 142(3):746-53. DOI: 10.1016/j.jep.2012.05.056
Source: PubMed


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.

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    • "Icariin (C 33 H 40 O 15 ; molecular weight: 676.67), a flavonoid isolated from Herba epimedii, is considered to be the main active component responsible for the actions of the plant. H. epimedii has been proven to be an effective remedy for cardiovascular diseases, osteoporosis, and tumors; moreover, and it can improve endocrine, immune, and cognitive functions12345678. In addition, H. epimedii has been traditionally used in China to treat erectile dysfunction[9]. "
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    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.
    Preview · Article · Jul 2014 · Molecules
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    • "Many Chinese researchers have been focused on icariin for many years, due to its low price, high abundance and multitherapeutic properties. Icariin could improve cognitive deficits and memory impairment, had anti-inflammatory, anti-tumor, and protect DNA damage effects, and even acts as a cGMPspecific prostaglandin E5 inhibitor which might be developed into an agent for the treatment of erection dysfunction (Wu et al. 2012; Urano and Tohda 2010; Wu et al. 2011; Wang et al. 2010; Zhao et al. 2007; Ning et al. 2006). Recently, the bone-strengthening activity of icariin has really attracted world-wide attention. "
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    ABSTRACT: The purpose of this systematic review is to assess the efficacy and pharmacological profiles of Herba Epimedii in osteoporosis therapy. Four databases were extensively retrieved that include two Chinese electronic databases (VIP Information and CNKI) and two English electronic databases (CA and MEDLINE). Herba Epimedii has been an important traditional herbal medicine for centuries in China and other Asian countries. Recently, quite a few pharmacological effects of Herba Epimedii, its extracts and active components have been identified that include improving bone health and cardiovascular function, regulating hormone level, modulating immunological function, and inhibiting tumor growth. The anti-osteoporosis activity of Herba Epimedii and its extracts have attracted world-wide attention. The literature search has revealed that a lot of studies have recently been carried out related to the bone-strengthening activity of Herba Epimedii and some of its active compounds, such as total flavonoids and icariin. Pharmacokinetic and toxicity studies have confirmed the efficacy and safety of Herba Epimedii and its most abundant active component icariin, while only a few authors have reviewed the anti-osteoporosis properties of the plants. So we summarize the work of various investigators on the effects of Herba Epimedii, its extracts and active components against osteoporosis. The underlying mechanism of osteoprotective action, derivatives of icariin, animal models and cell lines used in the research were also reviewed in this paper.
    Full-text · Article · Sep 2013 · Pharmazie
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    • "en insuffi - ciency in cardiovascular , neurodegenerative , and inflammatory diseases ( Deroo and Korach , 2006 ) . Epimedium brevicornum and icariin have been reported to protect against heart failure , reduce the inflammatory response , and improve learning and memory , but the mechanisms for these effects are still unknown ( Ma et al . , 2011 ; Wu et al . , 2012 ) . The estrogenic activity of Epimedium brevicornum Fig . 3 . Effect of icariin on estrogen biosynthesis in KGN cells . ( A ) The chemical structure of icariin . ( B ) KGN cells seeded in 24 - well plates were pretreated with icariin at the indicated concentration for 3 h . The cells were then supplemented with 10 nM testosterone for a"
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    ABSTRACT: ETHNOPHARMACOLOGICAL RELEVANCE: Epimedium brevicornum Maxim (E. brevicornum) has long been used for the treatment of osteoporosis in China and other Asian countries. However, the mechanism behind the antiosteoporotic activity of this medicinal plant is not fully understood. AIM OF THE STUDY: The present study was designed to investigate the effects of 5 widely used antiosteoporotic medicinal plants (E. brevicornum, Cuscuta chinensis, Rhizoma drynariae, Polygonum multiflorum, and Ligustrum lucidum) on the production of estrogen and identify the bioactive compounds responsible for the estrogen biosynthesis-promoting effect. MATERIALS AND METHODS: Human ovarian granulosa-like KGN cells were used to evaluate estrogen biosynthesis, and the production of 17β-estradiol was quantified by magnetic particle-based enzyme-linked immunosorbent assay (ELISA) kit. Further, the mRNA expression of aromatase was determined by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR), and the protein expression of aromatase was detected by western blotting. The activity of alkaline phosphatase (ALP) in rat osteoblastic UMR-106 cells was measured using p-nitrophenyl sodium phosphate assay. RESULTS: Among the 5 antiosteoporotic medicinal plants, the extract of E. brevicornum was found to significantly promote estrogen biosynthesis in KGN cells. Icariin, the major compound in E. brevicornum, was identified to be the active compound for the estrogen biosynthesis-promoting effect. Icariin promoted estrogen biosynthesis in KGN cells in a concentration- and time-dependant manner and enhanced the mRNA and protein expressions of aromatase, which is the only enzyme for the conversion of androgens to estrogens in vertebrates. Further study showed that icariin also promoted estrogen biosynthesis and ALP activity in osteoblastic UMR-106 cells. CONCLUSIONS: These results show that the promotion of estrogen biosynthesis is a novel effect of E. brevicornum, and icariin could be utilized for the prevention and treatment of osteoporosis.
    Full-text · Article · Dec 2012 · Journal of ethnopharmacology
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