Background Icafiine is a flavonoid isolated from a traditional Chinese medicine Epimedium pubescens and is the main active compound of it. Recently, Epimedium pubescens was found to have a therapeutic effect on osteop...Background Icafiine is a flavonoid isolated from a traditional Chinese medicine Epimedium pubescens and is the main active compound of it. Recently, Epimedium pubescens was found to have a therapeutic effect on osteoporosis. But the mechanism is unclear. The aim of the study was to research the effect of Icariine on the proliferation and differentiation of human osteoblasts. Methods Human osteoblasts were obtained by inducing human marrow mesenchymal stem cells （hMSCs） directionally and were cultured in the presence of vadous concentrations of Icariine. 3-（4,5-dimethylthiazol-2-yl）-2,5- diphenyltetrazolium bromide （MTT） test was used to observe the effect of Icariine on cell proliferation. The activity of alkaline phosphatase （ALP） and the amount of calcified nodules were assayed to observe the effect on cell differentiation. The expression of bone morphogenetic protein 2 （BMP-2） mRNA was detected by reverse transcriptase-polymerase chain reaction （RT-PCR）. Results Icadine （20 μg/ml） increased significantly the proliferation of human osteoblasts. And, IcarUne （10 μg/ml and 20 μg/ml） increased the activity of ALP and the amount of calcified nodules of human osteoblasts significantly （P〈0.05）. BMP-2 mRNA synthesis was elevated significantly in response to Icariine （20 μg/ml）. Conclusions Icadine has a direct stimulatory effect on the proliferation and differentiation of cultured human osteoblast cells in vitro, which may be mediated by increasing production of BMP-2 in osteoblasts.展开更多
In artificial joint replacement,osteoclast bone resorption induced by wear debris of the implant is a main reason for aseptic loosening.To extend the life of the prosthesis,detailed mechanisms of aseptic loosening and...In artificial joint replacement,osteoclast bone resorption induced by wear debris of the implant is a main reason for aseptic loosening.To extend the life of the prosthesis,detailed mechanisms of aseptic loosening and the ways to prevent it should be explored.The aim of this study was to investigate the in vitro effect of icariine on the bone resorption of osteoclasts induced by titanium particles.Macrophage colony stimulating factor(M-CSF)and receptor activator of NF-kB ligand(RANKL)were used to generate osteoclasts from RAW264.7 precursors.The proliferation of RAW264.7 precursors in the presence of different doses of icariine was evaluated by MTT assay.The cells were treated with titanium particles,titanium particles with icariine and culture medium only(control),respectively.At 48 h after treatment,the expression level of receptor activator of NF-kB(RANK)was detected by ELISA,and messenger RNA(mRNA)levels of tartrate-resistant acid phosphatase(TRAP),matrix metalloproteinase 9(MMP-9),carbonic anhydrase II(CAII)and Cathepsin K(CtsK)were determined by real-time polymerase chain reaction.Western blot was applied to analyze the expression levels of TRAP,RANK and CtsK.In addition,bone chips were cultured in the above conditions,and Toluidine blue staining was then employed to calculate the number and area of resorption pits in the bone chips.After treatment with icariine,expression level of RANK was significantly decreased in the RAW264.7 cell that induced by titanium particle and its cultural medium,mRNA and protein levels of TRAP,CAII,MMP-9 and CtsK were reduced as well.In addition,the numbers of bone resorption pits and areas on bone slices were both reduced by icariine challenging.Icariine could inhibit bone resorption of osteoclast induced by titanium particle,and it might be used as a promising drug for treating of aseptic loosening.展开更多
BACKGROUND Periodontitis is an inflammatory disease caused by the host’s immune response and various interactions between pathogens,which lead to the loss of connective tissue and bone.In recent years,mesenchymal ste...BACKGROUND Periodontitis is an inflammatory disease caused by the host’s immune response and various interactions between pathogens,which lead to the loss of connective tissue and bone.In recent years,mesenchymal stem cell(SC)transplantation technology has become a research hotspot,which can form periodontal ligament,cementum,and alveolar bone through proliferation and differentiation.AIM To elucidate the regulatory effects of WD repeat-containing protein 36(WDR36)on the senescence,migration,and osteogenic differentiation of periodontal ligament SCs(PDLSCs).METHODS The migration and chemotaxis of PDLSCs were detected by the scratch-wound migration test and transwell chemotaxis test.Alkaline phosphatase(ALP)activity,Alizarin red staining,calcium content,and real-time reverse transcription polymerase chain reaction(RT-qPCR)of key transcription factors were used to detect the osteogenic differentiation function of PDLSCs.Cell senescence was determined by senescence-associatedβ-galactosidase staining.RESULTS The 24-hour and 48-hour scratch-wound migration test and 48-hour transwell chemotaxis test showed that overexpression of WDR36 inhibited the migration/chemotaxis of PDLSCs.Simultaneously,WDR36 depletion promoted the migration/chemotaxis of PDLSCs.The results of ALP activity,Alizarin red staining,calcium content,and RTqPCR showed that overexpression of WDR36 inhibited the osteogenic differentiation of PDLSCs,and WDR36 depletion promoted the osteogenic differentiation of PDLSCs.Senescence-associatedβ-galactosidase staining showed that 0.1μg/mL icariin(ICA)and overexpression of WDR36 inhibited the senescence of PDLSCs,and WDR36 depletion promoted the osteogenic differentiation of PDLSCs.CONCLUSION WDR36 inhibits the migration and chemotaxis,osteogenic differentiation,and senescence of PDLSCs;0.1μg/mL ICA inhibits the senescence of PDLSCs.Therefore,WDR36 might serve as a target for periodontal tissue regeneration and the treatment of periodontitis.展开更多
BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To e...BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.展开更多
Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell...Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and proliferation.Autophagy expression was analyzed using monodansylcadaverine staining.Immunofluorescence and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR pathway.Cellular damage was examined using the lactate dehydrogenase assay.Moreover,cathepsin B and NLRP3 were detected by co-immunoprecipitation.Results:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of autophagy.The levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus curcumol.These changes were reversed upon overexpression of mTOR.Furthermore,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol group.Inhibiting cathepsin B reversed the regulatory effects of icariin plus curcumol.Conclusions:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin B.These findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.展开更多
Objective:To explore the mechanism by which icariin alleviates viral myocarditis.Methods:CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on ce...Objective:To explore the mechanism by which icariin alleviates viral myocarditis.Methods:CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability,inflammation,and apoptosis.Moreover,the effects of icariin on ferroptosis and TLR4 signaling were assessed.After AC16 cells were transfected with TLR4 overexpression plasmids,the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated.Results:Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α,IL-1β,IL-6,and IL-18.Flow cytometry revealed that icariin decreased apoptosis rate,and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes.Additionally,it suppressed ferroptosis including lipid peroxidation and ferrous ion,as well as the TLR4 signaling.However,TLR4 overexpression abrogated the modulatory effects of icariin.Conclusions:Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis.Further animal study is needed to verify its efficacy.展开更多
Objective Icariin(ICA)has a good neuroprotective effect and can upregulate neuronal basal autophagy in naturally aging rats.Mitochondrial dysfunction is associated with brain aging-related neurodegenerative diseases.A...Objective Icariin(ICA)has a good neuroprotective effect and can upregulate neuronal basal autophagy in naturally aging rats.Mitochondrial dysfunction is associated with brain aging-related neurodegenerative diseases.Abnormal opening of the mitochondrial permeability transition pore(mPTP)is a crucial factor in mitochondrial dysfunction and is associated with excessive autophagy.This study aimed to explore that ICA protects against neuronal injury by blocking the mPTP opening and down-regulating autophagy levels in a D-galactose(D-gal)-induced cell injury model.Methods A cell model of neuronal injury was established in rat pheochromocytoma cells(PC12 cells)treated with 200 mmol/L D-gal for 48 h.In this cell model,PC12 cells were pre-treated with different concentrations of ICA for 24 h.MTT was used to detect cell viability.Senescence associatedβ-galactosidase(SA-β-Gal)staining was used to observe cell senescence.Western blot analysis was performed to detect the expression levels of a senescence-related protein(p21),autophagy markers(LC3B,p62,Atg7,Atg5 and Beclin 1),mitochondrial fission and fusion-related proteins(Drp1,Mfn2 and Opa1),and mitophagy markers(Pink1 and Parkin).The changes of autophagic flow were detected by using mRFP-GFP-LC3 adenovirus.The intracellular ultrastructure was observed by transmission electron microscopy.Immunofluorescence was used to detect mPTP,mitochondrial membrane potential(MMP),mitochondrial reactive oxygen species(mtROS)and ROS levels.ROS and apoptosis levels were detected by flow cytometry.Results D-gal treatment significantly decreased the viability of PC12 cells,and markedly increased the SA-β-Gal positive cells as compared to the control group.With the D-gal stimulation,the expression of p21 was significantly up-regulated.Furthermore,D-gal stimulation resulted in an elevated LC3B II/I ratio and decreased p62 expression.Meanwhile,autophagosomes and autolysosomes were significantly increased,indicating abnormal activation of autophagy levels.In addition,in this D-gal-induced model of cell injury,the mPTP was abnormally open,the ROS generation was continuously increased,the MMP was gradually decreased,and the apoptosis was increased.ICA effectively improved mitochondrial dysfunction to protect against D-gal-induced cell injury and apoptosis.It strongly inhibited excessive autophagy by blocking the opening of the mPTP.Cotreatment with ICA and an mPTP inhibitor(cyclosporin A)did not ameliorate mitochondrial dysfunction.However,the protective effects were attenuated by cotreatment with ICA and an mPTP activator(lonidamine).Conclusion ICA inhibits the activation of excessive autophagy and thus improves mitochondrial dysfunction by blocking the mPTP opening.展开更多
Objective To explore the therapeutic effect and mechanism of Bushen Tiansui Decoction(补肾填髓方,BSTSD)and its active component icariin on Alzheimer’s disease(AD).Methods(i)Animal experiments.This study conducted exp...Objective To explore the therapeutic effect and mechanism of Bushen Tiansui Decoction(补肾填髓方,BSTSD)and its active component icariin on Alzheimer’s disease(AD).Methods(i)Animal experiments.This study conducted experiments using specific pathogen-free(SPF)grade male C57BL/6J wild-type(WT)mice and APP/PS1 double transgenic mice.The animals were divided into three groups:WT group(WT mice,n=5,receiving distilled wa-ter daily),APP/PS1 group(APP/PS1 double transgenic mice,n=5,receiving distilled water daily),and BSTSD group[APP/PS1 double transgenic mice,n=5,treated with BSTSD suspen-sion at a dosage of 27 g/(kg·d)for 90 d].Cognitive function was assessed using the Morris wa-ter maze(MWM).Post-experiment,hippocampal tissues were collected for analysis of pyra-midal cell and synaptic morphology through hematoxylin-eosin(HE)staining and transmis-sion electron microscopy(TEM).(ii)Cell experiments.The HT-22 cells were divided into con-trol group(untreated),Aβ_(25-35) group(treated with 20μmol/L Aβ_(25-35) for 24 h),icariin group(pre-treated with 20μmol/L icariin for 60 min,followed by 20μmol/L Aβ_(25-35) for an additional 24 h),and icariin+LY294002 group[treated with 20μmol/L icariin and 20μmol/L LY294002(an inhibitor of the phosphoinostitide 3-kinases(PI3K)signaling pathway)for 60 min,then exposed to 20μmol/L Aβ_(25-35) for 24 h],and cell viability was measured.Western blot was used to detect the expression levels of synapse-associated proteins[synaptophysin(SYP)and post-synaptic density-95(PSD-95)]and PI3K signaling pathway associated proteins[phosphorylat-ed(p)-PI3K/PI3K,p-protein kinase B(Akt)/Akt,and p-mechanistic target of rapamycin(mTOR)/mTOR].Results(i)Animal experiments.Compared with APP/PS1 group,BSTSD group showed that escape latency was significantly shortened(P<0.01)and the frequency of crossing the origi-nal platform was significantly increased(P<0.01).Morphological observation showed that pyramidal cells in the hippocampal CA1 region were arranged more regularly,nuclear stain-ing was uniform,and vacuole-like changes were reduced after BSTSD treatment.TEM showed that the length of synaptic active zone in BSTSD treatment group was increased com-pared with APP/PS1 group(P<0.01),and the width of synaptic gap was decreased(P<0.01).(ii)Cell experiments.Icariin had no obvious toxicity to HT-22 cells when the concentration was not more than 20μmol/L(P>0.05),and alleviated the cell viability decline induced by Aβ_(25-35)(P<0.01).Western blot results showed that compared with Aβ_(25-35) group,the ratios of p-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR in icariin group were significantly increased(P<0.01),while the protein expression levels of SYP and PSD-95 were increased(P<0.01).These effects were blocked by LY294002(P<0.01).Conclusion BSTSD and icariin enhance cognitive function and synaptic integrity in AD mod-els and provide potential therapeutic strategies through activation of the PI3K/Akt/mTOR pathway.展开更多
Icariin is the most prevalent component of the medicinal herb Herba Epimedii.Icariin exhibits many medicinal properties,including anti-cancer impact and osteoprotective and neuroprotective effects.The goal of this stu...Icariin is the most prevalent component of the medicinal herb Herba Epimedii.Icariin exhibits many medicinal properties,including anti-cancer impact and osteoprotective and neuroprotective effects.The goal of this study was to use bibliometric analysis to find and describe the top 100 papers about Icariin that had received the most citations.The Science Citation Index-Expanded(SCI-E)of the Web of Science Core Collection was used to find publications on Icariin(WoSCC).Descriptive analysis was conducted using VOSviewer software.There were 1473 articles about Icariin in all.The top 100 papers were published between 1996 and 2024 and received citations in the range of 55 to 390.The country that has contributed the most to Icariin research is China(84).The most productive institution was Hehai University.The most published journal was Phytomedicine.The research hotspots of Icariin mainly focus on the following aspects:research on Icariin treatment of sex hormone-related osteoporosis and erectile function;The effect of Icariin on cells by regulating oxidative stress,apoptosis,and proliferation;the mechanism of Icariin in the treatment of cancer;the neuroprotective effect of Icariin in central nervous diseases,such as Alzheimer's disease,Parkinson's disease,and depression.Future research should focus on further elucidating Icariin's anti-tumor effects,its application in cartilage tissue engineering and orthopedic biomaterials,and developing novel drug delivery systems to enhance its bioavailability.This research contributed essential knowledge to the study of Icariin.These results may be used in new study areas and to direct drug development.展开更多
This article summarized the research progress on the antidepressant mechanism of icariin II,mainly elaborating on its mechanism from five aspects:GABAergic nervous system,inflammatory response,oxidative stress,neurotr...This article summarized the research progress on the antidepressant mechanism of icariin II,mainly elaborating on its mechanism from five aspects:GABAergic nervous system,inflammatory response,oxidative stress,neurotrophic factors,and neurotransmitters in the brain.Its clinical application value was further explored to provide a theoretical basis for the development and utilization of icariin II in treating depression.展开更多
To investigate the effects of icariin （ICA） on angiotensin Ⅱ（Ang Ⅱ）-induced injury in human umbilical vein endothelial cells line （ECV-304）. The ECV-304 cells were cultured in vitro. After 24 h incubating with...To investigate the effects of icariin （ICA） on angiotensin Ⅱ（Ang Ⅱ）-induced injury in human umbilical vein endothelial cells line （ECV-304）. The ECV-304 cells were cultured in vitro. After 24 h incubating with icariin, the model of AngⅡ-induced injury in ECV-304 was established. The cell viability （MTT method）, Lactate dehydrogenase （LDH） release and Nitric oxide （NO） production in the medium, the capacity of scavenging superoxide anion radicals （O2^-） and hydroxyl radicals （.OH） were measured. The activities of superoxide dismutase （SOD）, total nitric oxide synthase （T-NOS）, inducible nitric oxide synthase （iNOS） and constitutive nitric oxide synthase （cNOS） in the cells were determined. Compared with the Ang Ⅱ-treated group, ICA can significantly raise the viability of EC, increase the activities of SOD, T-NOS and cNOS, increase the production of NO, enhance the capacity of scavenging superoxide anion radicals （ O2^- ） and hydroxyl radicals（.OH）, and lower LDH leakage and iNOS activity. The results suggest that ICA can protect endothelial cells （ECV-304） from Ang II-induced injury.展开更多
A composite material was fabricated by applying a biodegradable drug delivery coating,consisting of poly（3-hydroxyburyrate-co-3-hydroxyvalerate）（PHBV） and icariin,to an anodic oxidized titanium plate.The coating w...A composite material was fabricated by applying a biodegradable drug delivery coating,consisting of poly（3-hydroxyburyrate-co-3-hydroxyvalerate）（PHBV） and icariin,to an anodic oxidized titanium plate.The coating was prepared by evaporating chloroform solution containing PHBV and icariin on the titanium plate under vacuum condition.Icariin/PHBV coated titanium plates significantly enhance the proliferation of MG-63 cells compared with the PHBV coated and anodic oxidized ones.Increased icariin contained in the coating displays an elevated influence on cell proliferation.The results show that icariin gradually releases from the coating to cells mainly through the phospholipid-based cellular membrane instead of the culture medium.The overall results suggest that the novel icariin/PHBV coating can be used to enhance the bioactivity of titanium based orthopedic implants.展开更多
Aim: To clarify the mechanism of the therapeutic action of icariin on erectlile dysfunction (ED). Methods: PDE5 was isolated from the human platelet and PDE4 from the rat liver tissue using the FPLC system (Pharmacia,...Aim: To clarify the mechanism of the therapeutic action of icariin on erectlile dysfunction (ED). Methods: PDE5 was isolated from the human platelet and PDE4 from the rat liver tissue using the FPLC system (Pharmacia, Milton Keynes, UK) and the Mono Q column. The inhibitory effects of icariin on PDE5 and PDE4 activities were investigated by the two-step radioisotope procedure with [3H]-cGMP/[3H]-cAMP. Papaverine served as the control drug. Results: Icariin and papaverine showed dose-dependent inhibitory effects on PDE5 and PDE4 activities. The IC50 of Icariin and papaverine on PDE5 were 0.432 μmol/L and 0.680μmol/L, respectively and those on PDE4, 73.50 μmol/L and 3.07μmol/L, respectively. The potencies of selectivity of icariin and papaverine on PDE5 (PDE4/PDE5 of IC50) were 167.67 times and 4.54 times, respectively. Conclusion: Icariin is a cGMP-specific PDE5 inhibitor that may be developed into an oral effective agent for the treatment of ED.展开更多
Aim： To investigate the effect of icariin on erectile function and the expression of nitric oxide synthase （NOS） isoforms in castrated rats. Methods： Thirty-two adult male Wistar rats were randomly divided into on...Aim： To investigate the effect of icariin on erectile function and the expression of nitric oxide synthase （NOS） isoforms in castrated rats. Methods： Thirty-two adult male Wistar rats were randomly divided into one shamoperated group （A） and three castrated groups （B, C and D）. One week after surgery, rats were treated with normal saline （groups A and B） or oral icariin （1 mg/[kg·day] for group C and 5 mg/[kg·day] for group D） for 4 weeks. One week after treatment, the erectile function of the rats was assessed by measuring intracavernosal pressure （ICP） during electrostimulation of the cavernosal nerve. The serum testosterone （ST） levels, the percent of smooth muscle （PSM） in trabecular tissue, and the expression of mRNA and proteins of neuronal nitric oxide synthase （nNOS）, inducible nitric oxide synthase （iNOS）, endothelial nitric oxide synthase （eNOS） and phosphodiesterase V （PDES） in corpus cavernosum （CC） were also evaluated. Results： ICP, PSM, ST and the expression of nNOS, iNOS, eNOS and PDE5 were significantly decreased in group B compared with those in group A （P 〈 0.01）. However, ICE PSM and the expression of nNOS and iNOS were increased in groups C and D compared with those in group B （P 〈 0.05）. Changes in ST and the expression of eNOS and PDE5 were not significant （P 〉 0.05） in groups C and D compared with those in group B. Conclusion： Oral treatment with icariin （〉 98.6 % purity） for 4 weeks potentially improves erectile function. This effect is correlated with an increase in PSM and the expression of certain NOS in the CC of castrated rats. These results suggest that icariin may have a therapeutic effect on erectile dysfunction.展开更多
Aim： To evaluate the testosterone mimetic properties of icariin. Methods： Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each： the control g...Aim： To evaluate the testosterone mimetic properties of icariin. Methods： Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each： the control group （C）, the model group （M）, the icariin group （ICA） and the testosterone group （T）. The reproductive system was damaged by cyclophosphamide （intraperitoneal injection, 20 mg/kg·day） for 5 consecutive days for groups M, ICA and T, at the sixth day, ICA （gastric gavage, 200 mg/kg·day） for the ICA group and sterandryl （subcutaneous injection, 5 rag/rat.day） for the T group for 7 consecutive days, respectively. The levels of serum testosterone, luteinizing hormone （LH）, follicle stimulating hormone （FSH）, serum bone Gla-protein （BGP） and tartrate-resistant acid phosphatase activity in serum （StrACP） were determined. The histological changes of the testis and the penis were observed by microscope with hematoxylin-eosin （HE） staining and terminal deoxynucleotidyl transferase biotin-dUTP-X nick end labeling （TUNEL）, respectively. Results： （1） Icariin improved the condition of reproductive organs and increased the circulating levels of testosterone. （2） Icariin treatment also improved the steady-state serum BGP and might have promoted bone formation. At the same time, it decreased the serum levels of StrACP and might have reduced the bone resorption. （3） Icarrin suppressed the extent of apoptosis of penile cavernosal smooth muscle cells. Conclusion： Icariin has testosterone mimetic properties and has therapeutic potential in the management of hypoandrogenism.展开更多
Increasing evidence indicates that disruption of normal iron homeostasis may contribute to pathological development of Alzheimer＇s disease.Icariin,astragalus,and puerarin have been shown to suppress iron overload in ...Increasing evidence indicates that disruption of normal iron homeostasis may contribute to pathological development of Alzheimer＇s disease.Icariin,astragalus,and puerarin have been shown to suppress iron overload in the cerebral cortex and improve spatial learning and memory disorders in Alzheimer＇s disease mice,although the underlying mechanism remains unclear.In the present study,APPswe/PS1ΔE9 transgenic mice were administered icariin,astragalus,and puerarin（120,80,and 80 mg/kg,respectively,once a day,for 3 months）.Iron levels were detected by flame atomic absorption spectroscopy.Interleukin-1β,interleukin-6,and tumor necrosis factor-α levels were measured in the cerebral cortex by enzyme linked immunosorbent assay.Glutathione peroxidase and superoxide dismutase activity and malondialdehyde content were determined by colorimetry.Our results demonstrate that after treatment,iron levels and malondialdehyde content are decreased,while glutathione peroxidase and superoxide dismutase activities are increased.Further,interleukin-1β,interleukin-6,and tumor necrosis factor-α levels were reduced.These results confirm that compounds of icariin,astragalus,and puerarin may alleviate iron overload by reducing oxidative stress and the inflammatory response.展开更多
Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ ...Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.展开更多
Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the ther- apeutic effects of local admini...Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the ther- apeutic effects of local administration of icariin, a major component of Epimedium extract, on peripheral nerve regeneration. A poly（lactic-co-glycolic acid） biological conduit sleeve was used to bridge a 5 mm right sciatic nerve defect in rats, and physiological saline, nerve growth factor, icariin suspension, or nerve growth factor-releasing microsphere suspension was injected into the defect. Twelve weeks later, sciatic nerve conduction velocity and the number of myelinated fibers were notably greater in the rats treated with icariin suspension or nerve growth factor-releasing microspheres than those that had received nerve growth factor or physiological saline. The effects of icariin suspension were similar to those of nerve growth factor-releasing microspheres. These data suggest that icariin acts as a nerve growth factor-releasing agent, and indicate that local ap- plication of icariin after spinal injury can promote peripheral nerve regeneration.展开更多
Icariin, the major active component of Chinese medicinal herb epimedium brevicornum maxim, is used widely in traditional Chinese medicine for the treatment of neurological diseases. However, the effects of icariin on ...Icariin, the major active component of Chinese medicinal herb epimedium brevicornum maxim, is used widely in traditional Chinese medicine for the treatment of neurological diseases. However, the effects of icariin on myelin inhibitory factors are as yet unclear. In the present study, administration of icariin at 20 mg/kg showed a marked reduction in neurological deficit of middle cerebral artery occlusion rats. Icariin exhibited better inhibitory effects on myelin inhibitory factors： Nogo-A, myelin-associated glycoprotein and oligodendrocyte myelin glycoprotein in ischemia regions of middle cerebral artery occlusion rats compared with monosialotetrahexosylganglioside. These results indicate that icariin exhibits potent inhibitory effects on expression of myelin inhibitors after middle cerebral artery occlusion-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both Nogo-A, myelin-associated glycopretein and oligodendrocyte myelin glycoprotein activation, followed by the enhancement of axonal sprouting and regeneration, resulting in neurological functional recovery.展开更多
文摘Background Icafiine is a flavonoid isolated from a traditional Chinese medicine Epimedium pubescens and is the main active compound of it. Recently, Epimedium pubescens was found to have a therapeutic effect on osteoporosis. But the mechanism is unclear. The aim of the study was to research the effect of Icariine on the proliferation and differentiation of human osteoblasts. Methods Human osteoblasts were obtained by inducing human marrow mesenchymal stem cells （hMSCs） directionally and were cultured in the presence of vadous concentrations of Icariine. 3-（4,5-dimethylthiazol-2-yl）-2,5- diphenyltetrazolium bromide （MTT） test was used to observe the effect of Icariine on cell proliferation. The activity of alkaline phosphatase （ALP） and the amount of calcified nodules were assayed to observe the effect on cell differentiation. The expression of bone morphogenetic protein 2 （BMP-2） mRNA was detected by reverse transcriptase-polymerase chain reaction （RT-PCR）. Results Icadine （20 μg/ml） increased significantly the proliferation of human osteoblasts. And, IcarUne （10 μg/ml and 20 μg/ml） increased the activity of ALP and the amount of calcified nodules of human osteoblasts significantly （P〈0.05）. BMP-2 mRNA synthesis was elevated significantly in response to Icariine （20 μg/ml）. Conclusions Icadine has a direct stimulatory effect on the proliferation and differentiation of cultured human osteoblast cells in vitro, which may be mediated by increasing production of BMP-2 in osteoblasts.
基金This work was supported by grants from Natural Science Foundation of China(81302986)Young Foundation of Fujian Province Health Department,China(no.2007-2-37)Bureau of Science and Technology,Fuzhou(no.2009-G-104).
文摘In artificial joint replacement,osteoclast bone resorption induced by wear debris of the implant is a main reason for aseptic loosening.To extend the life of the prosthesis,detailed mechanisms of aseptic loosening and the ways to prevent it should be explored.The aim of this study was to investigate the in vitro effect of icariine on the bone resorption of osteoclasts induced by titanium particles.Macrophage colony stimulating factor(M-CSF)and receptor activator of NF-kB ligand(RANKL)were used to generate osteoclasts from RAW264.7 precursors.The proliferation of RAW264.7 precursors in the presence of different doses of icariine was evaluated by MTT assay.The cells were treated with titanium particles,titanium particles with icariine and culture medium only(control),respectively.At 48 h after treatment,the expression level of receptor activator of NF-kB(RANK)was detected by ELISA,and messenger RNA(mRNA)levels of tartrate-resistant acid phosphatase(TRAP),matrix metalloproteinase 9(MMP-9),carbonic anhydrase II(CAII)and Cathepsin K(CtsK)were determined by real-time polymerase chain reaction.Western blot was applied to analyze the expression levels of TRAP,RANK and CtsK.In addition,bone chips were cultured in the above conditions,and Toluidine blue staining was then employed to calculate the number and area of resorption pits in the bone chips.After treatment with icariine,expression level of RANK was significantly decreased in the RAW264.7 cell that induced by titanium particle and its cultural medium,mRNA and protein levels of TRAP,CAII,MMP-9 and CtsK were reduced as well.In addition,the numbers of bone resorption pits and areas on bone slices were both reduced by icariine challenging.Icariine could inhibit bone resorption of osteoclast induced by titanium particle,and it might be used as a promising drug for treating of aseptic loosening.
文摘BACKGROUND Periodontitis is an inflammatory disease caused by the host’s immune response and various interactions between pathogens,which lead to the loss of connective tissue and bone.In recent years,mesenchymal stem cell(SC)transplantation technology has become a research hotspot,which can form periodontal ligament,cementum,and alveolar bone through proliferation and differentiation.AIM To elucidate the regulatory effects of WD repeat-containing protein 36(WDR36)on the senescence,migration,and osteogenic differentiation of periodontal ligament SCs(PDLSCs).METHODS The migration and chemotaxis of PDLSCs were detected by the scratch-wound migration test and transwell chemotaxis test.Alkaline phosphatase(ALP)activity,Alizarin red staining,calcium content,and real-time reverse transcription polymerase chain reaction(RT-qPCR)of key transcription factors were used to detect the osteogenic differentiation function of PDLSCs.Cell senescence was determined by senescence-associatedβ-galactosidase staining.RESULTS The 24-hour and 48-hour scratch-wound migration test and 48-hour transwell chemotaxis test showed that overexpression of WDR36 inhibited the migration/chemotaxis of PDLSCs.Simultaneously,WDR36 depletion promoted the migration/chemotaxis of PDLSCs.The results of ALP activity,Alizarin red staining,calcium content,and RTqPCR showed that overexpression of WDR36 inhibited the osteogenic differentiation of PDLSCs,and WDR36 depletion promoted the osteogenic differentiation of PDLSCs.Senescence-associatedβ-galactosidase staining showed that 0.1μg/mL icariin(ICA)and overexpression of WDR36 inhibited the senescence of PDLSCs,and WDR36 depletion promoted the osteogenic differentiation of PDLSCs.CONCLUSION WDR36 inhibits the migration and chemotaxis,osteogenic differentiation,and senescence of PDLSCs;0.1μg/mL ICA inhibits the senescence of PDLSCs.Therefore,WDR36 might serve as a target for periodontal tissue regeneration and the treatment of periodontitis.
基金Supported by the Postdoctoral Fellowship Program of China Postdoctoral Science Foundation,No.GZC20231088President Foundation of The Third Affiliated Hospital of Southern Medical University,China,No.YP202210.
文摘BACKGROUND Icariin(ICA),a natural flavonoid compound monomer,has multiple pharmacological activities.However,its effect on bone defect in the context of type 1 diabetes mellitus(T1DM)has not yet been examined.AIM To explore the role and potential mechanism of ICA on bone defect in the context of T1DM.METHODS The effects of ICA on osteogenesis and angiogenesis were evaluated by alkaline phosphatase staining,alizarin red S staining,quantitative real-time polymerase chain reaction,Western blot,and immunofluorescence.Angiogenesis-related assays were conducted to investigate the relationship between osteogenesis and angiogenesis.A bone defect model was established in T1DM rats.The model rats were then treated with ICA or placebo and micron-scale computed tomography,histomorphometry,histology,and sequential fluorescent labeling were used to evaluate the effect of ICA on bone formation in the defect area.RESULTS ICA promoted bone marrow mesenchymal stem cell(BMSC)proliferation and osteogenic differentiation.The ICA treated-BMSCs showed higher expression levels of osteogenesis-related markers(alkaline phosphatase and osteocalcin)and angiogenesis-related markers(vascular endothelial growth factor A and platelet endothelial cell adhesion molecule 1)compared to the untreated group.ICA was also found to induce osteogenesis-angiogenesis coupling of BMSCs.In the bone defect model T1DM rats,ICA facilitated bone formation and CD31hiEMCNhi type H-positive capillary formation.Lastly,ICA effectively accelerated the rate of bone formation in the defect area.CONCLUSION ICA was able to accelerate bone regeneration in a T1DM rat model by inducing osteogenesis-angiogenesis coupling of BMSCs.
基金supported by Natural Science Foundation of Hunan Province(No.2023JJ40511)Excellent Youth Project of Scientific Research Program of Hunan Education Department(No.22B0370)+2 种基金Project of Traditional Chinese Medicine Administration of Hunan Province(No.B2023034)Science and Technology Development Foundation of Beijing Hospital of Traditional Chinese Medicine Affiliated to Capital Medical University(No.LYYB202214)Hunan Provincial Hygiene and Health Commission Health Research Project(No.W20243165).
文摘Objective:To examine the effect of icariin plus curcumol on prostate cancer cells PC3 and elucidate the underlying mechanisms.Methods:We employed the Cell Counting Kit 8 assay and colony formation assay to assess cell viability and proliferation.Autophagy expression was analyzed using monodansylcadaverine staining.Immunofluorescence and Western blot analyses were used to evaluate protein expressions related to autophagy,pyroptosis,and the mTOR pathway.Cellular damage was examined using the lactate dehydrogenase assay.Moreover,cathepsin B and NLRP3 were detected by co-immunoprecipitation.Results:Icariin plus curcumol led to a decrease in PC3 cell proliferation and an enhancement of autophagy.The levels of LC3-Ⅱ/LC3-Ⅰand beclin-1 were increased,while the levels of p62 and mTOR were decreased after treatment with icariin plus curcumol.These changes were reversed upon overexpression of mTOR.Furthermore,3-methyladenine resulted in a decrease in inflammatory cytokines,pyroptosis-related protein levels,and lactate dehydrogenase concentration,compared to the icariin plus curcumol group.Inhibiting cathepsin B reversed the regulatory effects of icariin plus curcumol.Conclusions:Icariin plus curcumol demonstrates great potential as a therapeutic agent for castration-resistant prostate cancer by enhancing autophagy via the mTOR pathway and promoting pyroptosis mediated by cathepsin B.These findings provide valuable insights into the molecular mechanisms underlying the therapeutic potential of icariin and curcumol for prostate cancer treatment.
基金supported by Affiliated Hospital of Youjiang Medical University for Nationalities(No.Y20212615).
文摘Objective:To explore the mechanism by which icariin alleviates viral myocarditis.Methods:CVB3-induced cardiomyocytes were used as an in vitro model of viral myocarditis to assess the effects of icariin treatment on cell viability,inflammation,and apoptosis.Moreover,the effects of icariin on ferroptosis and TLR4 signaling were assessed.After AC16 cells were transfected with TLR4 overexpression plasmids,the role of TLR4 in mediating the regulatory effect of icariin in viral myocarditis was investigated.Results:Icariin significantly elevated cell viability and reduced inflammatory factors TNF-α,IL-1β,IL-6,and IL-18.Flow cytometry revealed that icariin decreased apoptosis rate,and the protein expression of Bax and cleaved caspase 3 and 9 in CVB3-induced cardiomyocytes.Additionally,it suppressed ferroptosis including lipid peroxidation and ferrous ion,as well as the TLR4 signaling.However,TLR4 overexpression abrogated the modulatory effects of icariin.Conclusions:Icariin mitigates CVB3-induced myocardial injury by inhibiting TLR4-mediated ferroptosis.Further animal study is needed to verify its efficacy.
基金supported by the Natural Science Foundation of Yichang City of China(No.A23-1-075).
文摘Objective Icariin(ICA)has a good neuroprotective effect and can upregulate neuronal basal autophagy in naturally aging rats.Mitochondrial dysfunction is associated with brain aging-related neurodegenerative diseases.Abnormal opening of the mitochondrial permeability transition pore(mPTP)is a crucial factor in mitochondrial dysfunction and is associated with excessive autophagy.This study aimed to explore that ICA protects against neuronal injury by blocking the mPTP opening and down-regulating autophagy levels in a D-galactose(D-gal)-induced cell injury model.Methods A cell model of neuronal injury was established in rat pheochromocytoma cells(PC12 cells)treated with 200 mmol/L D-gal for 48 h.In this cell model,PC12 cells were pre-treated with different concentrations of ICA for 24 h.MTT was used to detect cell viability.Senescence associatedβ-galactosidase(SA-β-Gal)staining was used to observe cell senescence.Western blot analysis was performed to detect the expression levels of a senescence-related protein(p21),autophagy markers(LC3B,p62,Atg7,Atg5 and Beclin 1),mitochondrial fission and fusion-related proteins(Drp1,Mfn2 and Opa1),and mitophagy markers(Pink1 and Parkin).The changes of autophagic flow were detected by using mRFP-GFP-LC3 adenovirus.The intracellular ultrastructure was observed by transmission electron microscopy.Immunofluorescence was used to detect mPTP,mitochondrial membrane potential(MMP),mitochondrial reactive oxygen species(mtROS)and ROS levels.ROS and apoptosis levels were detected by flow cytometry.Results D-gal treatment significantly decreased the viability of PC12 cells,and markedly increased the SA-β-Gal positive cells as compared to the control group.With the D-gal stimulation,the expression of p21 was significantly up-regulated.Furthermore,D-gal stimulation resulted in an elevated LC3B II/I ratio and decreased p62 expression.Meanwhile,autophagosomes and autolysosomes were significantly increased,indicating abnormal activation of autophagy levels.In addition,in this D-gal-induced model of cell injury,the mPTP was abnormally open,the ROS generation was continuously increased,the MMP was gradually decreased,and the apoptosis was increased.ICA effectively improved mitochondrial dysfunction to protect against D-gal-induced cell injury and apoptosis.It strongly inhibited excessive autophagy by blocking the opening of the mPTP.Cotreatment with ICA and an mPTP inhibitor(cyclosporin A)did not ameliorate mitochondrial dysfunction.However,the protective effects were attenuated by cotreatment with ICA and an mPTP activator(lonidamine).Conclusion ICA inhibits the activation of excessive autophagy and thus improves mitochondrial dysfunction by blocking the mPTP opening.
基金Hunan Provincial Natural Science Foundation of China(2022JJ40220)Health Commission of Hunan Province(B202303106781)Hunan Administration of Traditional Chinese Medicine(2021192).
文摘Objective To explore the therapeutic effect and mechanism of Bushen Tiansui Decoction(补肾填髓方,BSTSD)and its active component icariin on Alzheimer’s disease(AD).Methods(i)Animal experiments.This study conducted experiments using specific pathogen-free(SPF)grade male C57BL/6J wild-type(WT)mice and APP/PS1 double transgenic mice.The animals were divided into three groups:WT group(WT mice,n=5,receiving distilled wa-ter daily),APP/PS1 group(APP/PS1 double transgenic mice,n=5,receiving distilled water daily),and BSTSD group[APP/PS1 double transgenic mice,n=5,treated with BSTSD suspen-sion at a dosage of 27 g/(kg·d)for 90 d].Cognitive function was assessed using the Morris wa-ter maze(MWM).Post-experiment,hippocampal tissues were collected for analysis of pyra-midal cell and synaptic morphology through hematoxylin-eosin(HE)staining and transmis-sion electron microscopy(TEM).(ii)Cell experiments.The HT-22 cells were divided into con-trol group(untreated),Aβ_(25-35) group(treated with 20μmol/L Aβ_(25-35) for 24 h),icariin group(pre-treated with 20μmol/L icariin for 60 min,followed by 20μmol/L Aβ_(25-35) for an additional 24 h),and icariin+LY294002 group[treated with 20μmol/L icariin and 20μmol/L LY294002(an inhibitor of the phosphoinostitide 3-kinases(PI3K)signaling pathway)for 60 min,then exposed to 20μmol/L Aβ_(25-35) for 24 h],and cell viability was measured.Western blot was used to detect the expression levels of synapse-associated proteins[synaptophysin(SYP)and post-synaptic density-95(PSD-95)]and PI3K signaling pathway associated proteins[phosphorylat-ed(p)-PI3K/PI3K,p-protein kinase B(Akt)/Akt,and p-mechanistic target of rapamycin(mTOR)/mTOR].Results(i)Animal experiments.Compared with APP/PS1 group,BSTSD group showed that escape latency was significantly shortened(P<0.01)and the frequency of crossing the origi-nal platform was significantly increased(P<0.01).Morphological observation showed that pyramidal cells in the hippocampal CA1 region were arranged more regularly,nuclear stain-ing was uniform,and vacuole-like changes were reduced after BSTSD treatment.TEM showed that the length of synaptic active zone in BSTSD treatment group was increased com-pared with APP/PS1 group(P<0.01),and the width of synaptic gap was decreased(P<0.01).(ii)Cell experiments.Icariin had no obvious toxicity to HT-22 cells when the concentration was not more than 20μmol/L(P>0.05),and alleviated the cell viability decline induced by Aβ_(25-35)(P<0.01).Western blot results showed that compared with Aβ_(25-35) group,the ratios of p-PI3K/PI3K,p-Akt/Akt and p-mTOR/mTOR in icariin group were significantly increased(P<0.01),while the protein expression levels of SYP and PSD-95 were increased(P<0.01).These effects were blocked by LY294002(P<0.01).Conclusion BSTSD and icariin enhance cognitive function and synaptic integrity in AD mod-els and provide potential therapeutic strategies through activation of the PI3K/Akt/mTOR pathway.
基金supported by the Natural Science Foundation of Sichuan Province(2023NSFSC1799)the Science and Technology Development Fund of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine(21ZS05,23YY07).
文摘Icariin is the most prevalent component of the medicinal herb Herba Epimedii.Icariin exhibits many medicinal properties,including anti-cancer impact and osteoprotective and neuroprotective effects.The goal of this study was to use bibliometric analysis to find and describe the top 100 papers about Icariin that had received the most citations.The Science Citation Index-Expanded(SCI-E)of the Web of Science Core Collection was used to find publications on Icariin(WoSCC).Descriptive analysis was conducted using VOSviewer software.There were 1473 articles about Icariin in all.The top 100 papers were published between 1996 and 2024 and received citations in the range of 55 to 390.The country that has contributed the most to Icariin research is China(84).The most productive institution was Hehai University.The most published journal was Phytomedicine.The research hotspots of Icariin mainly focus on the following aspects:research on Icariin treatment of sex hormone-related osteoporosis and erectile function;The effect of Icariin on cells by regulating oxidative stress,apoptosis,and proliferation;the mechanism of Icariin in the treatment of cancer;the neuroprotective effect of Icariin in central nervous diseases,such as Alzheimer's disease,Parkinson's disease,and depression.Future research should focus on further elucidating Icariin's anti-tumor effects,its application in cartilage tissue engineering and orthopedic biomaterials,and developing novel drug delivery systems to enhance its bioavailability.This research contributed essential knowledge to the study of Icariin.These results may be used in new study areas and to direct drug development.
文摘This article summarized the research progress on the antidepressant mechanism of icariin II,mainly elaborating on its mechanism from five aspects:GABAergic nervous system,inflammatory response,oxidative stress,neurotrophic factors,and neurotransmitters in the brain.Its clinical application value was further explored to provide a theoretical basis for the development and utilization of icariin II in treating depression.
基金National "Ninth five-year" Key Technology R&D Programme of China (Grant No.99-929-01-31)
文摘To investigate the effects of icariin （ICA） on angiotensin Ⅱ（Ang Ⅱ）-induced injury in human umbilical vein endothelial cells line （ECV-304）. The ECV-304 cells were cultured in vitro. After 24 h incubating with icariin, the model of AngⅡ-induced injury in ECV-304 was established. The cell viability （MTT method）, Lactate dehydrogenase （LDH） release and Nitric oxide （NO） production in the medium, the capacity of scavenging superoxide anion radicals （O2^-） and hydroxyl radicals （.OH） were measured. The activities of superoxide dismutase （SOD）, total nitric oxide synthase （T-NOS）, inducible nitric oxide synthase （iNOS） and constitutive nitric oxide synthase （cNOS） in the cells were determined. Compared with the Ang Ⅱ-treated group, ICA can significantly raise the viability of EC, increase the activities of SOD, T-NOS and cNOS, increase the production of NO, enhance the capacity of scavenging superoxide anion radicals （ O2^- ） and hydroxyl radicals（.OH）, and lower LDH leakage and iNOS activity. The results suggest that ICA can protect endothelial cells （ECV-304） from Ang II-induced injury.
基金Project (2010DFA32270) supported by International Science & Technology Cooperation Program of ChinaProject (2010) supported by Scientific Research Foundation for the Returned Oversea Scholars of Ministry of Education of China
文摘A composite material was fabricated by applying a biodegradable drug delivery coating,consisting of poly（3-hydroxyburyrate-co-3-hydroxyvalerate）（PHBV） and icariin,to an anodic oxidized titanium plate.The coating was prepared by evaporating chloroform solution containing PHBV and icariin on the titanium plate under vacuum condition.Icariin/PHBV coated titanium plates significantly enhance the proliferation of MG-63 cells compared with the PHBV coated and anodic oxidized ones.Increased icariin contained in the coating displays an elevated influence on cell proliferation.The results show that icariin gradually releases from the coating to cells mainly through the phospholipid-based cellular membrane instead of the culture medium.The overall results suggest that the novel icariin/PHBV coating can be used to enhance the bioactivity of titanium based orthopedic implants.
文摘Aim: To clarify the mechanism of the therapeutic action of icariin on erectlile dysfunction (ED). Methods: PDE5 was isolated from the human platelet and PDE4 from the rat liver tissue using the FPLC system (Pharmacia, Milton Keynes, UK) and the Mono Q column. The inhibitory effects of icariin on PDE5 and PDE4 activities were investigated by the two-step radioisotope procedure with [3H]-cGMP/[3H]-cAMP. Papaverine served as the control drug. Results: Icariin and papaverine showed dose-dependent inhibitory effects on PDE5 and PDE4 activities. The IC50 of Icariin and papaverine on PDE5 were 0.432 μmol/L and 0.680μmol/L, respectively and those on PDE4, 73.50 μmol/L and 3.07μmol/L, respectively. The potencies of selectivity of icariin and papaverine on PDE5 (PDE4/PDE5 of IC50) were 167.67 times and 4.54 times, respectively. Conclusion: Icariin is a cGMP-specific PDE5 inhibitor that may be developed into an oral effective agent for the treatment of ED.
基金The authors would like to acknowledge the National Nature Science Foundation of China(No.30070927)Beijing National Nature Science Foundation(No.7012023)for grants for this work.
文摘Aim： To investigate the effect of icariin on erectile function and the expression of nitric oxide synthase （NOS） isoforms in castrated rats. Methods： Thirty-two adult male Wistar rats were randomly divided into one shamoperated group （A） and three castrated groups （B, C and D）. One week after surgery, rats were treated with normal saline （groups A and B） or oral icariin （1 mg/[kg·day] for group C and 5 mg/[kg·day] for group D） for 4 weeks. One week after treatment, the erectile function of the rats was assessed by measuring intracavernosal pressure （ICP） during electrostimulation of the cavernosal nerve. The serum testosterone （ST） levels, the percent of smooth muscle （PSM） in trabecular tissue, and the expression of mRNA and proteins of neuronal nitric oxide synthase （nNOS）, inducible nitric oxide synthase （iNOS）, endothelial nitric oxide synthase （eNOS） and phosphodiesterase V （PDES） in corpus cavernosum （CC） were also evaluated. Results： ICP, PSM, ST and the expression of nNOS, iNOS, eNOS and PDE5 were significantly decreased in group B compared with those in group A （P 〈 0.01）. However, ICE PSM and the expression of nNOS and iNOS were increased in groups C and D compared with those in group B （P 〈 0.05）. Changes in ST and the expression of eNOS and PDE5 were not significant （P 〉 0.05） in groups C and D compared with those in group B. Conclusion： Oral treatment with icariin （〉 98.6 % purity） for 4 weeks potentially improves erectile function. This effect is correlated with an increase in PSM and the expression of certain NOS in the CC of castrated rats. These results suggest that icariin may have a therapeutic effect on erectile dysfunction.
文摘Aim： To evaluate the testosterone mimetic properties of icariin. Methods： Forty-eight healthy male Sprague-Dawley rats at the age of 15 months were randomly divided into four groups with 12 rats each： the control group （C）, the model group （M）, the icariin group （ICA） and the testosterone group （T）. The reproductive system was damaged by cyclophosphamide （intraperitoneal injection, 20 mg/kg·day） for 5 consecutive days for groups M, ICA and T, at the sixth day, ICA （gastric gavage, 200 mg/kg·day） for the ICA group and sterandryl （subcutaneous injection, 5 rag/rat.day） for the T group for 7 consecutive days, respectively. The levels of serum testosterone, luteinizing hormone （LH）, follicle stimulating hormone （FSH）, serum bone Gla-protein （BGP） and tartrate-resistant acid phosphatase activity in serum （StrACP） were determined. The histological changes of the testis and the penis were observed by microscope with hematoxylin-eosin （HE） staining and terminal deoxynucleotidyl transferase biotin-dUTP-X nick end labeling （TUNEL）, respectively. Results： （1） Icariin improved the condition of reproductive organs and increased the circulating levels of testosterone. （2） Icariin treatment also improved the steady-state serum BGP and might have promoted bone formation. At the same time, it decreased the serum levels of StrACP and might have reduced the bone resorption. （3） Icarrin suppressed the extent of apoptosis of penile cavernosal smooth muscle cells. Conclusion： Icariin has testosterone mimetic properties and has therapeutic potential in the management of hypoandrogenism.
基金supported by the National Natural Science Foundation of China,No.81273983
文摘Increasing evidence indicates that disruption of normal iron homeostasis may contribute to pathological development of Alzheimer＇s disease.Icariin,astragalus,and puerarin have been shown to suppress iron overload in the cerebral cortex and improve spatial learning and memory disorders in Alzheimer＇s disease mice,although the underlying mechanism remains unclear.In the present study,APPswe/PS1ΔE9 transgenic mice were administered icariin,astragalus,and puerarin（120,80,and 80 mg/kg,respectively,once a day,for 3 months）.Iron levels were detected by flame atomic absorption spectroscopy.Interleukin-1β,interleukin-6,and tumor necrosis factor-α levels were measured in the cerebral cortex by enzyme linked immunosorbent assay.Glutathione peroxidase and superoxide dismutase activity and malondialdehyde content were determined by colorimetry.Our results demonstrate that after treatment,iron levels and malondialdehyde content are decreased,while glutathione peroxidase and superoxide dismutase activities are increased.Further,interleukin-1β,interleukin-6,and tumor necrosis factor-α levels were reduced.These results confirm that compounds of icariin,astragalus,and puerarin may alleviate iron overload by reducing oxidative stress and the inflammatory response.
文摘Erectile dysfunction （ED） is a major complication of diabetes mellitus. Icariin has been shown to enhance erectile function through its bioactive form, icarisid Ih This study investigates the effects of icarisid Ⅱ on diabetic rats with ED and its potential mechanism viathe assessment of advanced glycosylation end products （AGEs）, autophagy, mTOR and the NO-cGMP pathway. Icarisid Ⅱ was extracted from icariin by an enzymatic method. In the control and diabetic ED groups, rats were administered normal saline; in the icarisid Ⅱ group, rats were administered icarisid Ⅱ intragastrically. Erectile function was evaluated by measuring intracavernosal pressure/mean arterial pressure （ICP/MAP）. AGE concentrations, nitric oxide synthase （NOS） activity and cGMP concentration were assessed by enzyme immunoassay. Cell proliferation was analysed using methyl thiazolyl tetrazolium assay and flow cytometry. Autophagosomes were observed by transmission electron microscopy, monodansylcadaverine staining and GFP-LC3 Iocalisation. The expression of NOS isoforms and key proteins in autophagy were examined by western blot. Our results have shown that Icarisid Ⅱ increased ICP/MAP values, the smooth muscle cell （SMC） growth curve, S phase and SMC/collagen fibril （SMC/CF） proportions and decreased Beclin 1 （P〈0.05）. Icarisid Ⅱ significantly increased the proliferative index and p-p70S6K（Thr389） levels and decreased the numbers of autophagosomes and the levels of LC3-11 （P〈0.01）. Icarisid Ⅱ decreased AGE concentrations and increased cGMP concentration, NOS activity （P〈0.05） and cNOS levels （P〈0.01） in the diabetic ED group. Therefore, Icarisid Ⅱ constitutes a promising compound for diabetic ED and might be involved in the upregulation of SMC proliferation and the NO-cGMP pathway and the downregulation of AGEs, autophagy and the mTOR pathway.
基金supported by grants from the National Program on Key Basic Research Project of China(973 Program),No.2014CB542200the National Natural Science Foundation of China,No.31271284,81171146,31100860+1 种基金the Natural Science Foundation of Beijing of China,No.7142164Program for Innovative Research Team in University of Ministry of Education of China,No.IRT1201
文摘Our previous study showed that systemic administration of the traditional Chinese medicine Epimedium extract promotes peripheral nerve regeneration. Here, we sought to explore the ther- apeutic effects of local administration of icariin, a major component of Epimedium extract, on peripheral nerve regeneration. A poly（lactic-co-glycolic acid） biological conduit sleeve was used to bridge a 5 mm right sciatic nerve defect in rats, and physiological saline, nerve growth factor, icariin suspension, or nerve growth factor-releasing microsphere suspension was injected into the defect. Twelve weeks later, sciatic nerve conduction velocity and the number of myelinated fibers were notably greater in the rats treated with icariin suspension or nerve growth factor-releasing microspheres than those that had received nerve growth factor or physiological saline. The effects of icariin suspension were similar to those of nerve growth factor-releasing microspheres. These data suggest that icariin acts as a nerve growth factor-releasing agent, and indicate that local ap- plication of icariin after spinal injury can promote peripheral nerve regeneration.
基金the National Natural Science Foundation of China,No.30672745the Shandong Scientific Research and Technological Development Program,No.2006GG3202005
文摘Icariin, the major active component of Chinese medicinal herb epimedium brevicornum maxim, is used widely in traditional Chinese medicine for the treatment of neurological diseases. However, the effects of icariin on myelin inhibitory factors are as yet unclear. In the present study, administration of icariin at 20 mg/kg showed a marked reduction in neurological deficit of middle cerebral artery occlusion rats. Icariin exhibited better inhibitory effects on myelin inhibitory factors： Nogo-A, myelin-associated glycoprotein and oligodendrocyte myelin glycoprotein in ischemia regions of middle cerebral artery occlusion rats compared with monosialotetrahexosylganglioside. These results indicate that icariin exhibits potent inhibitory effects on expression of myelin inhibitors after middle cerebral artery occlusion-induced focal cerebral ischemia in vivo. This effect may be mediated, at least in part, by the inhibition of both Nogo-A, myelin-associated glycopretein and oligodendrocyte myelin glycoprotein activation, followed by the enhancement of axonal sprouting and regeneration, resulting in neurological functional recovery.
