Epimedium Brevicornum Research Articles

Pleiotropic Effects of Icariside II on the Cardiovascular System: Novel Applications of Ethnopharmacology in Targeting Vascular Remodeling.

Pleiotropic Effects of Icariside II on the Cardiovascular System: Novel Applications of Ethnopharmacology in Targeting Vascular Remodeling.

Autocrine Activity of Extracellular Vesicles Induced by Icariin and Its Effectiveness in Glucocorticoid-Induced Injury of Bone Microvascular Endothelial Cells.

Glucocorticoids could induce injury and apoptosis of bone microvascular endothelial cells (BMECs) in the femoral head, which is associated with the development of osteonecrosis and osteoporosis. Icariin is a prenylated flavonol glycoside isolated from Epimedium brevicornum, serving as the main active pharmaceutical constituent to treat bone loss. Currently, the impact of the autocrine activity of extracellular vesicles (EVs) induced by icariin on the glucocorticoid-induced injury of BMECs is still to be confirmed. In this study, EVs were isolated from BMECs treated with and without icariin by super-speed centrifugation. Although icariin treatment would not significantly change the size and total protein content of BMECs-derived EVs, expression of EVs-carried vascular endothelial growth factor (VEGF) and transforming growth factor β1 (TGF-β1) was enhanced and numerous miRNAs involved in cell proliferation and apoptosis were upregulated (e.g., hsa-miR-1469 and hsa-miR-133a-5p) or downregulated (e.g., hsa-miR-10b-5p) (p < 0.05). A total of 29 differentially expressed inflammatory factors were detected between the EVs secreted by BMECs from the Icariin-treated group and the Model group. The EVs secreted by BMECs could improve cell viability, decrease cell apoptosis, and promote cell migration and angiogenesis under the intervention of glucocorticoids. Meanwhile, icariin intervention could reinforce these protective effects of BMECs-derived EVs. To sum up, the present study indicates that icariin acts as a promising candidate for treating glucocorticoid-induced injury of BMECs and bone diseases, partially through the autocrine activity of EVs. In vivo or animal studies are still required to better understand the function of BMECs-derived EVs.

The neuroprotective effects of icariin on ageing, various neurological, neuropsychiatric disorders, and brain injury induced by radiation exposure.

Epimedium brevicornum Maxim, a Traditional Chinese Medicine, has been used for the treatment of impotence, sinew and bone disorders, “painful impediment caused by wind-dampness,” numbness, spasms, hypertension, coronary heart disease, menopausal syndrome, bronchitis, and neurasthenia for many years in China. Recent animal experimental studies indicate that icariin, a major bioactive component of epimedium may effectively treat Alzheimer’s disease, cerebral ischemia, depression, Parkinson’s disease, multiple sclerosis, as well as delay ageing. Our recent study also suggested that epimedium extract could exhibit radio-neuro-protective effects and prevent ionizing radiation-induced impairment of neurogenesis. This paper reviewed the pharmacodynamics of icariin in treating different neurodegenerative and neuropsychiatric diseases, ageing, and radiation-induced brain damage. The relevant molecular mechanisms and its anti-neuroinflammatory, anti-apoptotic, anti-oxidant, as well as pro-neurogenesis roles were also discussed.

Icariin attenuates renal fibrosis in chronic kidney disease by inhibiting interleukin-1β/transforming growth factor-β-mediated activation of renal fibroblasts.

Icariin (ICA) is a bioactive flavonoid extracted from Epimedium brevicornum Maxim and exhibits a variety of pharmacological activities including antiinflammatory and antioxidant effects. Recently, icariin has shown renoprotective role by inhibiting pathological matrix. However, the underlying mechanisms of the efficacy remain unknown. This study aimed to determine the effects of icariin on renal fibrosis and explore its molecular mechanisms. Chronic kidney disease (CKD) was induced in rats with 5/6 ablation and infarction (A/I) operation. Four weeks later, rats were treated with vehicle or 20 mg/kg (low dose) or 40 mg/kg (high dose) of icariin by daily gavage. Furthermore, to further elucidate the effect mechanisms of icariin, in vitro, NRK-49F cells stimulated by 8ng/ml IL-1β were treated with icariin in the presence or absence of SB431542 or the neutralizing antibody of transforming growth factor-β (TGF-β) for 24 h. We showed that icariin treatment for 8 weeks dose-dependently improved 5/6 (A/I)-induced kidney injury and fibrosis, and blocked the release of inflammatory cytokine IL-1β. In vitro, icariin inhibited IL-1β/TGF-β-mediated activation of renal fibroblasts. In summary, anti-fibrotic effects of icariin were interconnected with the inhibition of renal fibroblast activation caused by IL-1β/TGF-β signaling.

Epimedium brevicornumMaxim and its Efficacy in the Treatment of Sexual Dysfunction

Epimedium sp. is a famous plant as sexual enhancer. In Chinese Pharmacopeia, Five species of Epimedium brevicornum, E. sagittatum, E. pubescens, E. koreanum, and E. wushanense were recorded as Epimedium Herba (Yin Yang Huo). The aim of this review article was to evaluate the potential efficacy of E. brevicornum as a remedy for sexual dysfunction and infertility. For preparing of this manuscript, we searched in all accessible resources (PubMed, Science Direct, Wiley, Springer, and Google), books, thesis, and pharmacopeias. There are different traditional prescriptions containing E. brevicornum, which are recommended for the treatment of impotence and sexual disorders. Although, there is no clinical study on efficacy and safety of E. brevicornum on sexual functions, but animal and experimental analysis exhibited that E. brevicornum is an estrogenic plant and its flavonoid glycosides are inhibitors of phosphodiesterase 5 (PDE 5) and improved the erectile dysfunction, libido, impotence, sperm quality and fertility. Due to the lack of clinical study on the efficacy of E. brevicornum, designing the human clinical study on safety and efficacy of standard E. brevicornum can be the subject of future studies.

Back to nature: herbal treatment, environmental enrichment, and social play can protect against unpredictable chronic stress in Long-Evans rats (Rattus norvegicus).

The importance of integrative biobehavioral responses to complex challenges cannot be overlooked. In this study, the synergetic effects of icariin (a flavonoid present in the plant Epimedium brevicornum), natural enrichment (NaEn), and play behavior were investigated. Rats (n = 60) were assigned to standard housing or NaEn; these two groups were subsequently divided into controls, rats receiving icariin treatments, and rats receiving icariin and allowed to play with an individual from another cage. All rats were exposed to unpredictable mild stressors for 4 weeks. At the end of the treatment, a Forced Swim Task (FST) was conducted to assess emotional regulation during an inescapable acute challenge. Biological samples were collected weekly and before and after the FST to monitor endocrine changes. Corticosterone (CORT), dehydroepiandrosterone (DHEA), and testosterone (T) were assayed. We found that icariin had a significant effect on DHEA/CORT ratios and T levels. NaEn also had a significant effect on both CORT and DHEA, but not on T levels. Play did not appear to be significantly related to the endocrine changes. The strongest positive effects on emotional resilience were observed in NaEn rats that also received icariin. Our results confirmed that using multiple channels to stimulate adaptive responses can be effective in increasing the ability of an organism to face uncertainty. Considering how quickly our life can change due to unpredictable events, our data is instrumental to a better comprehension of the many aspects of integrative biobehavioral responses.

Therapeutic effects and mechanism of ferulic acid and icariin in mammary gland hyperplasia model rats via regulation of the ERK pathway

BackgroundFerulic acid (FA) and icariin (ICA), as the active compounds derived from Angelica sinensis and Epimedium brevicornum Maxim, respectively, have been shown to promote blood circulation, regulate menstruation, exhibit anti-inflammatory effects, and modulate estrogen levels. The aim of this study was to elucidate the possible mechanism of FA, ICA, and FA-ICA on estrogen-induced mammary gland hyperplasia (MGH) in rats.MethodsHematoxylin and eosin (HE) staining was performed to record the pathological changes in breast tissue, and enzyme-linked immunosorbent assay (ELISA) was utilized to determine the serum levels of luteinizing hormone (LH), PRL (prolactin), testosterone (T), estradiol (E2), follicular stimulating hormone (FSH), and progesterone (P). The message RNA (mRNA) expression levels of extracellular signal-regulated kinase 1 (ERK1), extracellular signal-regulated kinase 2 (ERK2), estrogen receptor (ER), and progesterone receptor (PR) were detected by real-time reverse transcription-polymerase chain reaction (RT-PCR) analysis. Furthermore, ER, phosphorylated-ER, PR, p-PR, ERK1/2, and p-ERK1/2 protein factors in the ERK signaling pathway were evaluated by Western blotting. Simultaneously, changes in breast height, diameter, body weight, and organ index were all recorded.ResultsWe found that FA and ICA could modulate the degree of breast swelling, and reduce the body weight, thymus index, and uterus index. Furthermore, it could also block the pathological changes of MGH, including the number of mammary lobules, and the proliferation or expansion of acini and ducts. Moreover, treatment with FA and ICA remarkably down-regulated the serum expression levels of LH, PRL, T, and E2, as well as the mRNA expression levels of ERα, PR, ERK1, and ERK2. Additionally, protein levels of ERα, p-ERα, PR, p-PR, ERK1/2, and p-ERK1/2 in breast tissue were down-regulated, however the serum content of FSH and P was up-regulated.ConclusionsOur outcomes revealed that FA and ICA might potentially inhibit ERα, PR, ERK1/2, and their phosphorylated proteins via the ERK signaling pathway, thus indicating a positive feedback control for the degree of breast hyperplasia.

Icariin inhibits the expression of IL-1β, IL-6 and TNF-α induced by OGD/R through the IRE1/XBP1s pathway in microglia

Context Icariin (ICA), a flavonol glycoside extracted from Epimedium brevicornum Maxim (Berberidaceae), has been proven to inhibit inflammatory response in ischaemic rats in our laboratory's previous work. However, its underlying mechanism is still unclear. Objective This study investigates the effects of ICA on endoplasmic reticulum (ER) stress mediated inflammation induced by cerebral ischaemia–reperfusion (I/R) injury in vitro. Materials and methods The primary cultured microglia were treated with oxygen-glucose deprivation (OGD) for 2 h followed by a 24 h reoxygenation. ICA (0.37, 0.74 and 1.48 μmol/L) administration was performed 1 h prior OGD and acting through 2 h OGD. The control group was cultured in normal conditions. At 24 h after reoxygenation, the expression of IRE1α, XBP1u, XBP1s, NLRP3 and caspase-1 was detected by western blotting (WB) and quantitative real-time (qRT) PCR; the expression of p-IRE1α was examined by WB; the expression of IL-1β, IL-6 and TNF-α was measured by WB and enzyme-linked immunosorbent assay (ELISA). Results ICA (0.37, 0.74 and 1.48 μmol/L) reduced the ratio of p-IRE1α/IRE1α, the mRNA level of IRE1α, the expression of XBP1u, XBP1s, NLRP3, caspase-1 at both the mRNA and protein level expression of IL-1β, IL-6 and TNF-α in OGD/R injured microglia. Overexpression of IRE1 significantly reversed the effects of ICA. Discussion and conclusions These results suggested that ICA might decrease the expression of IL-1β, IL-6 and TNF-α by inhibiting IRE1/XBP1s pathway. The anti-inflammatory effect of ICA may provide a potential therapeutic strategy for the treatment of brain injury after stroke.

Icariin Ameliorates Lower Back Pain in Rats via Suppressing the Secretion of Cytokine-Induced Neutrophil Chemoatractant-1.

Purpose To investigate whether icariin (ICA), a well-known medicine extracted from the stem and leaf of Epimedium brevicornum Maxim, had analgesic effect on lower back pain (LBP) in rats. Methods In a puncture-induced LBP rat model, the severity of LBP was quantified using the paw/foot withdrawal threshold method after intragastric administration of ICA at a dosage of 50 mg/kg/d or 100 mg/kg/d. The pain-related peptides of substance P (SP) and calcitonin gene-related peptide (CGRP) were also measured in intervertebral disc (IVD) tissue using RT-PCR after ICA treatment. In addition, the expression of cytokine-induced neutrophil chemoattractant-1 (CINC-1) in IVD was quantified using RT-PCR and ELISA examination. Results ICA treatment resulted in a significant amelioration of mechanical allodynia in a dose-response manner, and the analgesic effect could last for two weeks even during the washout period. More importantly, the mechanism of analgesic pharmacological effect in ICA was to suppress the upregulated CINC-1, the homolog of IL-8 in rats, which is a crucial proalgesic factor contributing to LBP, in IVDs. Conclusion ICA is a novel herbal extract to relieve LBP, and it may be a promising alternative pain killer in the future.

Study on the regulatory mechanism and experimental verification of icariin for the treatment of ovarian cancer based on network pharmacology

Ethnopharmacological relevanceHerba Epimedii (Berberidaceae) has the advantages of “nourishing the kidney and reinforcing the Yang”. Many species in this genus have long been used in traditional Chinese medicine (TCM) and have been used as anticancer drugs in traditional Chinese herbal medicine formulations. Icariin, a major flavonoid glycoside extracted from Epimedium brevicornum Maxim, has been widely proven to exert an inhibitory effect on ovarian cancer (OC), and icariin can induce apoptosis and inhibit invasion and migration. However, the underlying mechanism remains unclear, so further research is necessary to verify its traditional use. Aim of the studyThis study aimed to explore the regulatory mechanism of icariin in the biological network and signalling pathway of OC through network pharmacology and cytological experiments. MethodsPublic databases and R × 3.6.2 software were adopted to predict the potential targets, construct the protein-protein interaction (PPI) network, and perform Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. After the network pharmacological analysis, cytological experiments, real-time quantitative PCR (qPCR) and Western blot (WB) analyses were used to verify the key signalling pathway. ResultsThe targets related to treatment were TNF, MMP9, STAT3, PIK3CA, ERBB2, MTOR, IL2, PTGS2, KDR, and F2. GO and KEGG enrichment analyses indicated that various kinases and the PI3K/AKT signalling pathway were the most enriched molecules and pathways. Icariin inhibited OC SKOV3 cell proliferation, migration and invasion in vitro and promoted apoptosis by inhibiting the PI3K/AKT signalling pathway. ConclusionIcariin promotes apoptosis and suppresses SKOV3 cell activities through the PI3K-Akt signalling pathway. This research not only provides a theoretical and experimental basis for more in-depth studies but also offers an efficient method for the rational utilization of a series of icariin flavonoids as anti-tumour drugs.

Chemotherapeutic Potential of Epimedium brevicornum Extract: The cGMP-Specific PDE5 Inhibitor as Anti-Infertility Agent Following Long-Term Administration of Tramadol in Male Rats.

Epimedium brevicornum Maxim (EbM) is a well-known Chinese herb that has been widely used for the treatment of several diseases. The main purpose of this study is to examine the role of Epimedium brevicornum extract in certain andrological parameters in rats as a natural modulator for adverse viewpoints associated with chronic administration of tramadol (TAM). Fifty rats were categorized into five groups. Untreated rats were known as Group I, whereas rats in Groups II and III were administered 2.43 g/kg/day of E. brevicornum extract and 50 mg/kg/day of TAM for 130 consecutive days, respectively. Both of Groups IV and V were administered TAM for 65 successive days, followed by concomitant use of both drugs for another 65 days, with the E. brevicornum extract at doses of 0.81 and 2.43 g/kg/day, respectively. TAM showed an injurious effect on sperm attributes, serum hormones, tissue malondialdehyde, superoxide dismutase, and nitric oxide. Elevation of the apoptotic marker Bax and a reduction of Bcl2 were recorded. Histopathological abnormalities have been reported in rat testicles. Rats treated with E. brevicornum extract with TAM showed an improvement in all the parameters tested. It could be presumed that E. brevicornum extract plus TAM exhibits a promising effect on the enhancement of male anti-infertility effects.

Effects of icariin on cell injury and glucocorticoid resistance in BEAS-2B cells exposed to cigarette smoke extract.

Glucocorticoids (GCs) exert a therapeutic effect in numerous chronic inflammatory diseases. However, chronic obstructive pulmonary disease (COPD) tends to be GC-resistant. Icariin, a major component of flavonoids isolated from Epimedium brevicornum Maxim (Berberidaceae), significantly relieves symptoms in patients with COPD. However, the mechanism of action remains unclear and further investigation is required to establish whether it may serve as an alternative or complementary therapy for COPD. The aim of the present study was to determine the effects of icariin in human bronchial epithelial cells exposed to cigarette smoke extract (CSE) and to determine whether icariin reverses GC resistance. The results revealed that icariin significantly increased the proliferation of CSE-exposed cells. Furthermore, icariin significantly increased protein expression of the anti-inflammatory factor interleukin (IL)-10 and significantly decreased protein expression of the pro-inflammatory factors IL-8 and tumor necrosis factor α. Icariin also attenuated the expression of the cellular matrix remodelling biomarkers matrix metallopeptidase 9 and tissue inhibitor of metalloproteinase 1, and decreased the production of reactive oxygen species (ROS). In addition, icariin regulated the expression of GC resistance-related factors, such as GC receptors, histone deacetylase 2, nuclear factor erythroid-2-related factor 2 and nuclear factor κ B. The results obtained in the present study suggested that icariin may decrease CSE-induced inflammation, airway remodelling and ROS production by mitigating GC resistance. In conclusion, icariin may potentially be used in combination with GCs to increase therapeutic efficacy and reduce GC resistance in COPD.

Icariin protects against sodium azide-induced neurotoxicity by activating the PI3K/Akt/GSK-3β signaling pathway.

BackgroundIcariin (ICA) is one of the major active flavonoids extracted from the traditional Chinese herb Epimedium brevicornum Maxim and has been shown to have neuroprotective effects. This study was designed to investigate the effect of ICA on sodium azide (NaN3)-induced rat adrenal pheochromocytoma (PC12) cell damage and to further examine the underlying mechanisms.MethodsTo explore its possible mechanism, we used NaN3 (50 mM)-induced neuronal PC12 cell damage. Cell viability was evaluated by CCK-8 and lactate dehydrogenase (LDH) assays. Mitochondrial membrane potential (MMP) was detected by JC-1. Glucose concentration was assessed by the glucose oxidase method. The role of ICA in the PI3K/Akt/GSK-3β signaling pathway was explored by Western blotting.ResultsThe results indicate that pretreatment with ICA reduced NaN3-induced cell damage and significantly reduced the leakage rate of LDH in PC12 cells. ICA pretreatment increased the MMP and a decrease in glucose concentration indicate increased glucose consumption. Furthermore, the protein levels of p-PI3K (p85), PI3K-110α, p-Ser473-Akt and p-Ser9-GSK-3β were markedly decreased in PC12 cells after NaN3 treatment for 24 h, whereas these effects were reverted after pretreatment with ICA. Tau phosphorylation at the Ser396/404 and Thr217 sites was significantly decreased by pretreatment with ICA.ConclusionsThese results suggest that ICA protects against NaN3-induced neurotoxicity in PC12 cells by activating the PI3K/Akt/GSK-3β signaling pathway.

Icariside II suppresses cervical cancer cell migration through JNK modulated matrix metalloproteinase-2/9 inhibition in vitro and in vivo

Metastasis contributes a lot to cervical cancer high mortality rate. Icariside II is the principal component of Epimedium brevicornum Maxim and the major functional part to its therapeutic properties. However, the effects and mechanisms of Icariside II on cervical cancer metastasis remain unclear. Using female BALB/c mice with 60 mm3 tumors, we injected mice tail with 25 mg/kg body weight Icariside II or DMSO. After harvesting the tumor, immunohistochemistry and western blot were performed to detect MMP2/9 levels. Icariside II injection significantly inhibited MMP2/9 protein expression. The cell migration assays revealed that Icarisdie II inhibited the wound closure rate and the ability of Hela cell crossing the transwell chambers. Further, the key regulators in NF-κB and MAPK signaling pathway were detected in xenograft tumor and Hela cells by qPCR and western blot. JNK was screened out from several important signaling molecules, which had the same expression trend with MMP2/9. Finally, both 5 μM and 30 μM Icariside II weakened JNK-MMP2/9 signaling, despite the JNK activator Polyphyllin I and Anisomycin reversed the deficiencies. In this study, we proved that Icariside II can inhibit cervical cancer cells migration through JNK-MMP2/9 signaling pathway and is a prospective drug with high-chemopreventive effects on cervical cancer cell metastasis.

Benefits of Herbal Medicine on Bone Mineral Density in Osteoporosis: A Meta-Analysis of Randomized Controlled Trials.

Bone mineral density (BMD) has been validated not only for the diagnosis of osteoporosis but also for prediction of the risk of osteoporosis-related fractures. The purpose of this paper was to investigate the overall benefits of herbal medicines on BMD using a meta-analytic method. Systematic searches in PubMed, Medline, Cochrane Central, and China National Knowledge Infrastructure were performed for eligible studies. A meta-analysis was conducted to evaluate the benefits of herbal medicine treatment and conventional treatment for BMD. Herbal medicines frequently used for interventions were pooled in the analysis and further investigated. Seventeen studies were pooled in the meta-analysis and showed that BMD was higher in the herbal medicine group than in the control group (standardized mean difference [SMD]: 0.857; 95% confidence interval [CI]: 0.412 to 1.301). Significant benefits of herbal medicine for BMD were found in the lumbar spine, femoral neck, and femoral trochanter and in postmenopausal women (SMD: 0.600, 95% CI: 0.068 to 1.131) by subgroup analysis. Moreover, through the meta-regression analysis, the age at menopause and the menopause duration were found to influence the herbal intervention effects on BMD. In addition, the most prescribed medicine among the effective herbs in the pooled studies was found to be Epimedium brevicornum Maxim. This paper provides evidence that herbal medicine interventions increase BMD more than conventional treatments in individuals with osteoporosis, especially postmenopausal women. The results of this study suggest that herbal medicines are effective for increasing BMD in individuals with osteoporosis.

Icariside II inhibits tumorigenesis via inhibiting AKT/Cyclin E/ CDK 2 pathway and activating mitochondria-dependent pathway

Cervical cancer contributes largely in women cancer-related mortality. Herein, Icariside II, a flavonoid extracted from edible and pharmaceutical plant Epimedium brevicornum Maxim, exhibited significant anticancer activity on cervical cancer. At first, it was observed that Icariside II inhibited Hela cell proliferation at IC50 (9.2 μM) and the growth of Hela-originated xenografts in BALB/c nude mice. Next, we studied the underlying mechanisms of Icariside II from the aspects of cell growth and cell death. As for cell growth, Icariside II arrested cell cycle at G0/G1 phase through AKT/Cyclin E/CDK 2 from transcriptional and translational levels. As for cell death, Flow Cytometry and Immunofluorescence showed that Icariside II promoted cell death in a dose-dependet manner. And, Icariside II turned to activate the mitochondria-dependent pathway Caspase 9/Caspase 3 much more significantly than death receptor pathway Caspase 8/Caspase 3. Taken together, Icariside II presented anticancer effect on cervical cancer both in vitro and in vivo. Our study provides the evidence that Icariside II can be used as a suitable novel agent in cervical cancer treatment.

Icaritin, an inhibitor of beta-site amyloid cleaving enzyme-1, inhibits secretion of amyloid precursor protein in APP-PS1-HEK293 cells by impeding the amyloidogenic pathway.

BackgroundIcaritin (ICT) is a prenylflavonoid derivative from Epimedium brevicornum Maxim. ICT has been shown to have neuroprotective effects. We investigate how ICT affects secretion of amyloid precursor protein (APP).MethodsWe exposed APP-PS1-HEK293 cells to ICT to investigate its effect on beta-site amyloid cleaving enzyme (BACE)1. Cell viability was evaluated by MTT and lactate dehydrogenase (LDH) assays. The half-maximal inhibitory concentration (IC50) of ICT for BACE1 was measured using fluorescence resonance energy transfer. Effects of ICT on the mRNA expression of APP were assessed by quantitative polymerase chain reaction, and protein expression was measured by western blotting and immunofluorescence.ResultsIcaritin inhibited BACE1 activity and IC50 was 5.70 ± 1.09 μM. Compared with the control group, at ICT concentrations of 5 μM and 10 μM, the viability increased and LDH leakage decreased in APP-PS1-293 cells. Also, mRNA expression of A disintegrin and metalloproteinase domain-containing protein 10 (ADAM10) increased, while that of BACE1 and presenilin-1 (PS1) decreased, upon ICT treatment. Western blotting and immunofluorescence confirmed that protein expression of ADAM10, BACE1 and PS1 showed the same trend. Expression of the APP fragments sAPPβ and C-terminal fragment β decreased, while that of sAPPα increased, upon ICT treatment. Expression of amyloid β peptides in APP-PS1-HEK293 cells was lower in ICT-treated groups compared with that in the control group.ConclusionsIcaritin, as a BACE1 inhibitor, inhibits APP secretion in APP-PS1-HEK293 cells by impeding the amyloidogenic pathway.

Therapeutic Anabolic and Anticatabolic Benefits of Natural Chinese Medicines for the Treatment of Osteoporosis.

Osteoporosis is a bone disease characterized by increasing osseous fragility and fracture due to the reduced bone mass and microstructural degradation. Primary pharmacological strategies for the treatment of osteoporosis, hormone replacement treatment (HRT), and alendronate therapies may produce adverse side-effects and may not be recommended for long-term usage. Some classic and bone-specific natural Chinese medicine are very popularly used to treat osteoporosis and bone fracture effectively in clinical with their potential value in bone growth and development, but with few adverse side-effects. Current evidence suggests that the treatments appear to improve bone metabolism and attenuate the osteoporotic imbalance between bone formation and bone resorption at a cellular level by promoting osteoblast activity and inhibiting the effects of osteoclasts. The valuable therapies might, therefore, provide an effective and safer alternative to primary pharmacological strategies. Therefore, the purpose of this article is to comprehensively review these classic and bone-specific drugs in natural Chinese medicines for the treatment of osteoporosis that had been deeply and definitely studied and reported with both bone formation and antiresorption effects, including Gynochthodes officinalis (F.C.How) Razafim. & B.Bremer (syn. Morinda officinalis F.C.How), Curculigo orchioides Gaertn., Psoralea corylifolia (L.) Medik Eucommia ulmoides Oliv., Dipsacus inermis Wall. (syn. Dipsacus asperoides C.Y.Cheng & T.M.Ai), Cibotium barometz (L.) J. Sm., Velvet Antler, Cistanche deserticola Ma, Cuscuta chinensis Lam., Cnidium monnieri (L.) Cusson, Epimedium brevicornum Maxim, Pueraria montana (Lour.) Merr. and Salvia miltiorrhiza Bunge., thus providing evidence for the potential use of alternative Chinese medicine therapies to effectively treat osteoporosis.

Extraction, purification and anti-osteoporotic activity of a polysaccharide from Epimedium brevicornum Maxim. in vitro

Osteoporosis is the most widespread metabolic bone disease characterized by decreased bone mass and bone quality, and its diagnosis and treatment remains challenging. To date, medicinal plants have received increasing attention from researchers for researching effective and less toxic therapeutic ingredients, including polysaccharide, to treat osteoporosis. The present study aims to evaluate the osteoprotective effects of a polysaccharide (EBP) from Epimedium brevicornum in glucocorticoid-induced osteoporosis in vitro and investigate the underlying mechanism. EBP (25 and 100 μg/ml) pretreatment could significantly prevent decreased cell proliferation of osteoblasts (OBs) treated only with 100 μM of dexamethasone (Dex) via induction of apoptosis. The osteoblastic differentiation of EBP pretreatment on OBs at early and later phase was further confirmed by the increased alkaline phosphatase (ALP) activity and calcium content, respectively. Meanwhile, the increased expression of cleaved caspase-3 and Bax, as well as a decrease of Bcl-2 and the phosphorylation of PI3K, Akt and mTOR protein in Dex-treated OBs were totally reversed by EBP pretreatment. Moreover, the protein expression of Lrp-5, β-catenin, Runx2 and Osx were significantly up-regulated in the presence of EBP pretreatment. In conclusion, these results demonstrated that EBP pretreatment may be a potential therapeutic agent for patients with glucocorticoid-induced osteoporosis (GIO).

Icariin induces apoptosis by suppressing autophagy in tamoxifen-resistant breast cancer cell line MCF-7/TAM

BackgroundIcariin is a major component isolated from Epimedium brevicornum Maxim and has been reported to exhibit anti-tumor activity. However, whether icariin could reverse the acquired drug resistance in breast cancer remains largely unclear. Therefore, this study was designed to explore the antitumor effects of icariin and its underlying mechanisms in a tamoxifen-resistant breast cancer cell line MCF-7/TAM.Methods3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and Lactate dehydrogenase (LDH) assay were performed to determine the effects of icariin on cell viability and cell death. Cell cycle progression and apoptosis were detected by flow cytometry analysis. Transmission electron microscopy (TEM) assay was utilized to observe cell autophagy. The downstream protein levels were measured using western blotting.ResultsHere, we observed that icariin treatment not only inhibited the growth of MCF-7 but also has a potential function to overcome tamoxifen resistance in MCF-7/TAM. Moreover, icariin significantly induced cell cycle G0/G1 phase arrest and apoptosis, as well as suppressed autophagy. At molecular levels, icariin treatment remarkably down-regulated the expression levels of CDK2, CDK4, Cyclin D1, Bcl-2, LC3-1, LC3-II, AGT5, Beclin-1, but upregulated the expression levels of caspase-3, PARP and p62. Most importantly, we found inhibition of autophagy via 3-MA treatment could significantly enhance the effects of icariin on cell viability and apoptosis. Enhanced autophagy via autophagy related 5 (ATG5) overexpression could partially reverse the effects of icariin on cell viability and apoptosis.ConclusionThese results revealed that icariin might potentially be useful as an adjuvant agent in cancer chemotherapy to enhance the effect of tamoxifen through suppression of autophagy in vitro and provide insight into the therapeutic potential of icariin for the treatment of chemo-resistant breast cancer.