RESUMEN

Introduction: As inhibitors of advanced glycation end products (AGEs), such as pyridoxamine, significantly inhibit the development of retinopathy and neuropathy in rats with streptozotocin-induced diabetes, treatment with AGE inhibitors is believed to be a potential strategy for the prevention of aging, age-related diseases, and lifestyle-related diseases, including diabetic complications. In the present study, the MeOH extract of Epimedii Herba (EH; aerial parts of Epimedium spp.) was found to inhibit the formation of N ε -(carboxymethyl)lysine (CML) and N ω -(carboxymethyl) arginine (CMA) during the incubation of collagen-derived gelatin with ribose. Materials and methods: EH was purchased from Uchida Wakan-yaku Co., and a MeOH extract was prepared. Several steps of column chromatography purified the extract. Each fraction was tested for inhibitory activity by ELISA using monoclonal antibodies for CML and CMA. Results: After activity-guided fractionation and purification by column chromatography, three new prenylflavonoids [named Koreanoside L (1), Koreanoside E1 (2), and Koreanoside E2 (3)] and 40 known compounds (4-43) were isolated from EH, and their inhibitory effects against CML and CMA formation were tested. Among these, epimedokoreanin B (8), epimedonin E (21), epicornunin B (22), and epicornunin F (24) inhibited the formation of both CML and CMA, with epimedokoreanin B (8) having the most potent inhibitory effect among the isolated compounds. To obtain the structure-activity relationships of 8, the phenolic hydroxy groups of 8 were methylated by trimethylsilyl-diazomethane to afford the partially and completely methylated compounds of 8. Prenyl derivatives of propolis (artepillin C, baccharin, and drupanin) were used in the assay. Discussion: As only 8 showed significant activity among these compounds, the catechol group of the B ring and the two prenyl groups attached to the flavanone skeleton were essential for activity. These data suggest that 8 could prevent the clinical complications of diabetes and age-related diseases by inhibiting AGEs.

RESUMEN

Rheumatoid arthritis (RA) is a chronic, progressive inflammatory and systemic autoimmune disease resulting in severe joint destruction, lifelong suffering and considerable disability. Diverse prescriptions of traditional Chinese medicine (TCM) containing Epimedii Herba (EH) achieve greatly curative effects against RA. The present review aims to systemically summarize the therapeutic effect, pharmacological mechanism, bioavailability and safety assessment of EH to provide a novel insight for subsequent studies. The search terms included were "Epimedii Herba", "yinyanghuo", "arthritis, rheumatoid" and "Rheumatoid Arthritis", and relevant literatures were collected on the database such as Google Scholar, Pubmed, Web of Science and CNKI. In this review, 15 compounds from EH for the treatment of RA were summarized from the aspects of anti-inflammatory, immunoregulatory, cartilage and bone protective, antiangiogenic and antioxidant activities. Although EH has been frequently used to treat RA in clinical practice, studies on mechanisms of these activities are still scarce. Various compounds of EH have the multifunctional traits in the treatment of RA, so EH may be a great complementary medicine option and it is necessary to pay more attention to further research and development.

RESUMEN

Icariin is a primary active component of the traditional Chinese medicinal plant Epimedium grandiflorum. A range of pharmacological effects of icariin has been researched by modern science to explain its traditional medicinal uses. Attributing to the wide range of pharmacological properties like anti-osteoporosis, anti-inflammation, anti-oxidative stress, anti-depression, and anti-tumor property possessed by icariin, it is now being considered a potential therapeutic agent for a wide variety of disorders ranging from neoplasm, neurodegenerative disorders, osteoporosis, and cardiovascular diseases. Various signaling pathways including NFκB/NALP3, IGF-1, MiR-223-3p/ NALP3, TLR4/ NFκB, and WNT1/ß-catenin are involved in the different biological actions exerted by icariin. Apart from these pathways, PI3K-AKT (Phosphoinositide 3 kinase-Protein kinase B) and Nrf-2 (nuclear erythroid 2-related factor 2) signaling pathways are two important pathways that form the fundamental basis for the pharmaceutical efficacy of icariin. This review gives an overview of previous in vitro and in vivo studies that investigated the potential role of icariin via PI3K-AKT and Nrf-2 signaling pathways to provide greater insights into its potential clinical use in a variety of disorders.

Asunto(s)

Medicamentos Herbarios Chinos , Proteínas Proto-Oncogénicas c-akt , Antiinflamatorios/farmacología , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Flavonoides/farmacología , Flavonoides/uso terapéutico , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal

RESUMEN

Icariin is a biologically active substance in Epimedii herba that is used for the treatment of neurologic disorders. However, a comprehensive analysis of the molecular mechanisms of icariin is lacking. In this review, we present a brief history of the use of icariin for medicinal purposes; describe the active chemical components of Epimedii herba; and examine the evidence from experimental studies that have uncovered molecular targets of icariin in different diseases. We also constructed a protein-protein interaction network and carried out Gene Ontology and Kyoto Encyclopedia of Genes and Genomes functional enrichment analyses to predict the therapeutic actions of icariin in nervous system diseases including Alzheimer disease, Parkinson disease, ischemic stroke, depressive disorder, multiple sclerosis, glioblastoma, and hereditary spastic paraplegias. The results of our analyses can guide future studies on the application of icariin to the treatment of neurologic disorders.

Asunto(s)

Medicamentos Herbarios Chinos/química , Flavonoides/farmacología , Enfermedades del Sistema Nervioso/tratamiento farmacológico , Animales , Flavonoides/aislamiento & purificación , Humanos , Terapia Molecular Dirigida , Enfermedades del Sistema Nervioso/fisiopatología , Farmacología en Red , Mapas de Interacción de Proteínas

RESUMEN

It is usually a tedious task to profile the chemical composition of a given herbal medicine (HM) using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) due to the time-consuming sample preparation and laborious post-acquisition data processing procedures. Even worse, some labile compounds may face degradation risks when exposed to organic solvents for a relatively long period. As one of the most popular HMs, the promising therapeutic benefits of Epimedii Herba (Chinese name: Yinyanghuo) are well defined; however, the chemical profile, and in particular those flavonoids that have been claimed to be responsible for the efficacy, remains largely unknown. Attempts are devoted here to achieve direct LC-MS measurement and efficient post-acquisition data processing, and chemome comparison among three original sources of Epimedii Herba, such as Epimedium sagittatum (Esa), E. pubescens (Epu), and E. koreanum (Eko) was employed to illustrate the strategy utility. A home-made online liquid extraction (OLE) module was introduced at the front of the analytical column to comprehensively transfer the compounds from raw materials onto the LC-MS instrument. A mass defect filtering approach was programmed to efficiently mine the massive LC-MS dataset after which a miniature database was built involving all chemical information of flavonoids from the genus Epimedium to draw a pentagonal frame to rapidly capture potential quasi-molecular ions (mainly [M-H]-). A total of 99 flavonoids (66 in Esa, 84 in Eko, and 66 in Epu) were captured, and structurally annotated by summarizing the mass fragmentation pathways from the mass spectrometric data of authentic compounds and an in-house data library as well. Noteworthily, neutral loss of 144 Da was firstly assigned to the neutral cleavage of rhamnosyl residues. Significant species-differences didn't occur among their chemical patterns. The current study proposed a robust strategy enabling rapid chemical profiling of, but not limited to, HMs.

Asunto(s)

Epimedium/química , Flavonoides/química , China , Cromatografía Líquida de Alta Presión/métodos , Epimedium/metabolismo , Flavonoides/metabolismo , Medicina Tradicional China/métodos , Plantas Medicinales/química , Espectrometría de Masas en Tándem/métodos

RESUMEN

M2-like tumor-associated macrophages (TAMs) in the tumor tissues promote tumor progression by various mechanisms and represent possible targets of antitumor therapy. In the present study, we tested whether compounds from Epimedii Herba inhibit macrophage polarization to the M2/protumorigenic phenotype and prevent tumor progression, using human monocyte-derived macrophages (HMDMs) and an animal sarcoma model. Four Epimedii Herba-derived flavonoid compounds, namely, limonianin, epimedokoreanin B, icaritin, and desmethylicaritin, inhibited CD163 expression and interleukin (IL)-10 production, which are known M2 markers, suggesting that these compounds inhibit M2 polarization. Among these compounds, epimedokoreanin B and limonianin suppressed STAT3 activation in HMDMs. Notably, epimedokoreanin B also suppressed cell proliferation by blocking STAT3 activation in Saos-2 human sarcoma and LM8 mouse sarcoma cell lines. Furthermore, oral administration of epimedokoreanin B inhibited tumor growth in an LM8 tumor-bearing murine model. These results indicate that Epimedii Herba and Epimedii Herba-derived compounds, such as epimedokoreanin B, may be potentially new agents that can be used for the treatment and prevention of various malignant tumors. They may also be promising compounds for targeting the tumor microenvironment by inhibiting M2 polarization of the TAMs.

RESUMEN

Bone nonunion remains a challenge during the treatment of bone defect accompanied with infection. Epimedii herba is a widely used medicine in clinic to enhance bone healing. Epimedin C and icariin are the major flavonoid glycosides from Epimedii herba. Although the effects of these compounds have been reported, their different absorption and utilisation by osteoblasts remain unclear. In the present study, lipopolysaccharide (LPS)-induced osteoblast was adopted as the model cell to evaluate the effects of epimedin C and icariin. The intracellular and extracellular drug concentrations within 24 h were assayed by pipette tip solid-phase extraction and high-performance liquid chromatography, respectively. MTT, alkaline phosphatase (ALP) and calcified nodule staining were performed to identify and evaluate the effects of epimedin C and icariin on LPS-induced osteoblasts. The regulatory roles of epimedin C and icariin in the bone morphogenetic protein-2 (BMP-2)/Runt-related transcription factor 2 (Runx2) signalling pathway were investigated. The results revealed that epimedin C and icariin were not efficiently absorbed by LPS-induced osteoblasts. Nevertheless, they still had high utilisation efficiency after entering the cells. ALP activity, mineralisation and osteoblasts proliferation were enhanced by a high concentration of epimedin C and icariin. The suppressed expression of BMP-2 and Runx2 in LPS-induced osteoblasts was up-regulated significantly after treatment with epimedin C and icariin. These findings firstly illustrated the behavior of epimedin C and icariin from Epimedii herba on LPS-induced osteoblasts and the regulatory property on the expression of key genes and proteins of the BMP-2/Runx2 signalling pathway, which might be helpful for better understanding flavonoids' mechanism to enhance bone repair and improving their future application.

Asunto(s)

Proteína Morfogenética Ósea 2/metabolismo , Subunidad alfa 1 del Factor de Unión al Sitio Principal/metabolismo , Flavonoides/metabolismo , Transducción de Señal , Animales , Flavonoides/química , Flavonoides/farmacología , Lipopolisacáridos , Masculino , Osteoblastos/efectos de los fármacos , Osteoblastos/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , Ratas Sprague-Dawley

RESUMEN

OBJECTIVES: An anti-osteoporotic herbal formula ELP containing Epimedii Herba (E), Ligustri Lucidi Fructus (L) and Psoraleae Fructus (P) was studied to investigate the herb-herb interaction (or the possible synergistic effect) among each component and to identify the principal herbs in different modes of action. METHODS: Rat osteoblast-like UMR-106 cells proliferation, rat MSCs-derived osteoblastogenesis and RANKL-induced RAW 264.7 osteoclastogenesis were adopted to investigate the bone-forming activity and bone-degrading activity of the herbal extracts. In the statistical aspect, a modified Tallarida's approach was employed to assess the synergistic effects in herbal combinations. KEY FINDINGS: Psoraleae Fructus is the active herb for stimulating osteoblast proliferation, and mild synergy was detected in the pairwise combinations EL, LP and formula ELP. In osteoblastogenesis assay, E and L are the principal herbs for promoting osteoblast differentiation and significant synergy was detected in the pairwise combination EL. For inhibiting osteoclast formation, L is the active herb and significant synergy was detected in the 3-way combination ELP. CONCLUSIONS: The presence of E, L and P is essential for ELP formula as a whole to act against osteoporosis via enhancing bone formation and reducing bone reabsorption. An optimal dosage at 150 µg/ml was proposed for ELP based on our findings.

Asunto(s)

Conservadores de la Densidad Ósea/farmacología , Remodelación Ósea/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Epimedium , Ligustrum , Osteoblastos/efectos de los fármacos , Osteoclastos/efectos de los fármacos , Osteoporosis/tratamiento farmacológico , Psoralea , Fosfatasa Alcalina/metabolismo , Animales , Conservadores de la Densidad Ósea/aislamiento & purificación , Diferenciación Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Medicamentos Herbarios Chinos/aislamiento & purificación , Epimedium/química , Ligustrum/química , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Células Madre Mesenquimatosas/patología , Ratones , Osteoblastos/metabolismo , Osteoblastos/patología , Osteoclastos/metabolismo , Osteoclastos/patología , Osteoporosis/metabolismo , Osteoporosis/patología , Fitoterapia , Componentes Aéreos de las Plantas , Plantas Medicinales , Psoralea/química , Ligando RANK/farmacología , Células RAW 264.7 , Ratas , Ratas Sprague-Dawley

RESUMEN

Because inhibitors of advanced glycation end-products (AGEs), for example pyridoxamine, significantly inhibit the development of retinopathy and neuropathy in rats with streptozotocin-induced diabetes, treatment with AGE inhibitors is believed to be a potential strategy for the prevention of lifestyle-related diseases such as diabetic complications. In the present study, the MeOH extract of Epimedii Herba (EH; aerial parts of Epimedium spp.) was found to inhibit the formation of N (ε) -(carboxymethyl)lysine (CML) and N (ω) -(carboxymethyl)arginine (CMA) during incubation of collagen-derived gelatin with ribose. Furthermore, compounds with inhibitory effects against CML and CMA formation were isolated from EH. Two new prenylflavonoids (compounds 1 and 2) and two known compounds (3 and 4) were found to significantly inhibit the formation of both CML and CMA; compound 4 (epimedokoreanin B) had the strongest inhibitory effect of the isolated compounds. These data suggest that epimedokoreanin B could prevent clinical complications of diabetes by inhibiting AGEs.

Asunto(s)

Arginina/análogos & derivados , Complicaciones de la Diabetes/metabolismo , Medicamentos Herbarios Chinos/farmacología , Epimedium/química , Flavonoides/farmacología , Productos Finales de Glicación Avanzada/metabolismo , Lisina/análogos & derivados , Animales , Arginina/biosíntesis , Complicaciones de la Diabetes/prevención & control , Medicamentos Herbarios Chinos/aislamiento & purificación , Medicamentos Herbarios Chinos/uso terapéutico , Flavonoides/aislamiento & purificación , Flavonoides/uso terapéutico , Lisina/biosíntesis , Masculino , Fitoterapia , Componentes Aéreos de las Plantas , Prenilación , Ratas

RESUMEN

To observe the effect of Epimedii Herba alcohol extract (HE) on tumor growth of lung cancer by establishing the model of Lewis tumor-bearing mice, ELISA method was used to detect the levels of TNF-α, IL-10, IL-17, IL-2 in serum. Ki67 and P53 protein expression was detected in lung cancer tissues by using Western blot assay method and immunohistochemical assay method. The experimental results showed that HE has certain inhibitory effect on Lewis lung cancer tumor growth, and it can reduce the levels of TNF-α, IL-10 and IL-17 in serum, improve the level of IL-2,significantly decrease the expression of Ki67, and significantly increase P53 expression. HE has obvious inhibitory effect against lung cancer, and has the ability to improve immune regulating effect. This study reveals the anti-lung cancer effect of HE may be related to its ability of improving immunity, thus provides the basis for further research on anti-lung cancer effect of HE.

Asunto(s)

Carcinoma Pulmonar de Lewis/tratamiento farmacológico , Proliferación Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/administración & dosificación , Epimedium/química , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/inmunología , Animales , Carcinoma Pulmonar de Lewis/genética , Carcinoma Pulmonar de Lewis/inmunología , Carcinoma Pulmonar de Lewis/fisiopatología , Medicamentos Herbarios Chinos/aislamiento & purificación , Femenino , Humanos , Interleucina-10/genética , Interleucina-10/inmunología , Pulmón/efectos de los fármacos , Pulmón/inmunología , Neoplasias Pulmonares/genética , Ratones , Ratones Endogámicos C57BL , Factor de Necrosis Tumoral alfa/genética , Factor de Necrosis Tumoral alfa/inmunología

RESUMEN

Objective: To assess the potential effect of the low glycosides fraction from Epimedii Herba (LGFEH) on UMR-106 cells and zebrafish model with osteoporosis induced by Prednisolone. Methods: The MTT assay was used to detect the effect of LGFEH on the proliferation of UMR-106 cells, and at the same time, the influence of LGFEH to the UMR-106 cells differentiation was observed through testing the ALP activity of UMR-106 cells using biochemical assays. Zebrafish larvae at 3 d post fertilization were divided into blank control group, 0.5% DMSO group, Prednisolone group, etidronate disodium group, and LGFEH (1, 2, 4, 8, and 16 μg/mL) groups. All groups were incubated in 24-well plates for 9 d until execution, and then zebrafish skeleton was anesthetized and fixed for staining with alizarin red. Quantitative analysis of the stained area was performed by microscopic inspection and digital imaging methods to reflect the amount of bone mineralization. Results: The LGFEH significantly increased both proliferation and ALP activities of UMR-106 cells. Furthermore, compared with model group, head skeleton mineral area and IOD of the LGFEH groups were significantly increased. Conclusion: Our results indicate that the LGFEH might be beneficial for treating osteoporosis.

RESUMEN

Objective: To study the therapeutic effect and mechanism of alcohol extract from Epimedii Herba (AEEH) on ovariectomy-induced osteoporosis in rats. Methods: Ipriflavone Tablets (200 mg/kg) and different doses of AEEH (170 and 85 mg/kg) were given for 8 weeks by ig administration, from 4 weeks after ovariectomization. Then, the protein expression of serum ALP, StrACP, femoral osteoprotegerin (OPG), and osteoclast differentiation factor (RANKL) was evaluated by biochemical assay kits and immunohistochemical evaluation; The mechanical properties of the tibia were determined by three point bending test method. Finally, the distal femoral trabecular bone parameters and the 3D reconstruction, trabecular bone of the 3D graphics were intuitively illustrated, and the effect of AEEH on rats suffered from osteoporosis role was observed by micro-CT. Results: Treatment with AEEH (170 mg/kg) significantly inhibited serum ALP and StrACP levels. Furthermore, AEEH also could significantly increase OPG protein expression while reduce RANKL protein expression compared with OVX rats. In addition, it could effectively improve the biomechanical properties of the tibia and the parameters of the trabecular bone of the femur, respectively. Conclusion: AEEH is effective in treating ovariectomy-induced osteoporosis in rats and the mechanism is mainly achieved by promoting the activity of osteoblast and inhibiting the activity of osteoclast.

RESUMEN

Objective: To establish a method for the content identification of chemical constituents in Qiling Wenshen Xiaonang Formula by using UPLC-ESI-IT-TOF/MS, which can infer the potential active ingredients in the formula, combining with literature. Methods: The chromatography separation was performed on a Waters ACQUITY UPLC BEH C18 column (100 mm × 2.1 mm, 1.7 μm) with acetonitrile-0.1% formic acid in water by gradient elution. Electrospray ionization (ESI) source was applied and operated in both positive and negative ion mode. Results: A total of 36 chemical constituents were identified by ESI/MS through comparison on chemical standards and literature data, including 19 flavonoids, 11 phenolic acids, four triterpenoid saponins, one sesquiterpene glycoside, and one alkaloid. Conclusion: This study introduces a comprehensive analysis method for chemical ingredients in Qiling Wenshen Xiaonang Formula, and lays a foundation for the further analysis on the substance basis research. The results provide a significant guidance for the substance basis research and quality control of compound Chinese materia medica.

RESUMEN

Objective: To establish a method of quantitative analysis of multi-components by single marker (QAMS) for determining the flavonoids in Epimedii Herba and improve the level of quality control of Epimedii Herba by applying multi-index components control. Methods: To detect a relative correction factor (RCF) of epimendin A, epimendin B, epimendin C, and icariin at detection wavelength of 270 nm by HPLC in the range of a linear, to investigate the reproducibility of RCF in different chromatographic columns and different instruments as well, to consider icariin as an internal standard, to calculate the contents of epimendin A, epimendin B, and epimendin C in Epimedii Herba by using RCF; Meanwhile, to analyze the content of the four components in 100 Epimedii Herba by external standard method (ESM) and verify the accuracy and scientificalness of QAMS. Results: The RCF had a good reproducibility, which were 1.352, 1.384, and 1.340. The values of RSD were less than 5%; No significant differences were found in the quantitative results of epimendin A, epimendin B, and epimendin C determined by using RCF and ESM. Conclusion: This method could be accurate and reliable, simple and feasible, which could save the reference and costs of testing. It further validates that this approach can be used as a quality control method for the determination of multi-component index in Epimedii Herba.

RESUMEN

To observe the effect of Epimedii Herba alcohol extract (HE) on tumor growth of lung cancer by establishing the model of Lewis tumor-bearing mice, ELISA method was used to detect the levels of TNF-α, IL-10, IL-17, IL-2 in serum. Ki67 and P53 protein expression was detected in lung cancer tissues by using Western blot assay method and immunohistochemical assay method. The experimental results showed that HE has certain inhibitory effect on Lewis lung cancer tumor growth, and it can reduce the levels of TNF-α, IL-10 and IL-17 in serum, improve the level of IL-2,significantly decrease the expression of Ki67, and significantly increase P53 expression. HE has obvious inhibitory effect against lung cancer, and has the ability to improve immune regulating effect. This study reveals the anti-lung cancer effect of HE may be related to its ability of improving immunity, thus provides the basis for further research on anti-lung cancer effect of HE.

RESUMEN

Epimedii herba is a traditional Chinese medicine for the treatment of osteoporosis. Epimedin A, B and C and icariin are the primary effective ingredients of this medicine. In this study, a simple and low-cost method based on pipette tip solid-phase extraction, high-performance liquid chromatography separation, and diode array detection has been developed for the simultaneous analysis of four flavonoids (epimedin A, B and C and icariin) from Epimedii herba in rat serum samples. In this novel extraction configuration, the sorbents were placed between a filter (hollow fiber) and the pipette tip. Pipette tip solid-phase extraction has several advantages compared to conventional extraction methods: faster extraction time (6.0min); lower sample volume (100µL); lower solvent volume (100µL); and less solvent waste. Under the optimum extraction conditions, the method showed good linearity (0.05-10.0µgmL(-1)), acceptable intra- and inter precision (RSD<6%), low limits of quantification (0.027-0.045µgmL(-1)) and satisfactory relative recoveries (98.63-103.18%). This method was successfully applied to investigate the pharmacokinetics of the major flavonoids in Epimedii herba extract after oral administration to rats (10gkg(-1) body weight). The primary pharmacokinetic parameters for rats were determined as follows: Cmax, 0.45-4.11µgmL(-1); Tmax, 0.21-0.26h; t1/2α, 0.06-0.12h; t1/2ß, 2.02-3.48h; AUC0-∞: 0.50-2.58µghmL(-1); CL, 19.53-44.72Lkg(-1)h(-1); and MRT0-∞, 2.25-3.77h. The developed method has the potential to promulgate the pharmacokinetics and provide more information for clinical applications.

Asunto(s)

Cromatografía Líquida de Alta Presión/métodos , Medicamentos Herbarios Chinos/farmacocinética , Flavonoides/sangre , Flavonoides/farmacocinética , Extracción en Fase Sólida/métodos , Animales , Medicamentos Herbarios Chinos/administración & dosificación , Medicamentos Herbarios Chinos/química , Epimedium , Femenino , Flavonoides/química , Modelos Lineales , Masculino , Ratas , Ratas Wistar , Reproducibilidad de los Resultados , Sensibilidad y Especificidad

RESUMEN

The objective of this study is to characterize a toxicity of Epimedii Herba (EH) in F344 rats and to find a dose levels for the 13 weeks toxicity study. EH is well known as medicinal herb in many Asian countries for traditional medicines of antibacterial and antiviral effects, estrogenic and antiestrogenic effects, and for treatment of osteoporosis, hypotensives, fatigue, kidney disorders, and related complications. However, the indispensable and basic information of toxicological evaluation of EH extract is insufficient to support its safe use. Therefore, we conducted toxicological evaluation of this drug in compliance with OECD and MFDS guideline in this study. The extract of EH was administered orally to F344 rats at dose levels of 0, 500, 1000, 2000, 3500, and 5000 mg/kg/day for 2 weeks. Each group was composed of 5 male and female rats. In this study, there were no treatment of EH-related adverse changes in clinical observations, mortality, body weights, food consumption, urinalysis, gross finding at necropsy, and organ weight examination. Total red blood cell count, hematocrit, mean corpuscular hemoglobin concentration, total cholesterol, and phospholipid were decreased in males and females at 5000 mg/kg/day compared to the control animals. Mean corpuscular volume and reticulocyte counts were increased in males and females at 5000 mg/kg/day compared to control animals. Therefore, we recommend that dose level of 5000 mg/kg/day is a highest treatment group in 13-week EH extract exposure study for further toxicity assessment.

Asunto(s)

Animales , Femenino , Humanos , Masculino , Ratas , Pueblo Asiatico , Berberidaceae , Peso Corporal , Colesterol , Adaptabilidad , Recuento de Eritrocitos , Índices de Eritrocitos , Moduladores de los Receptores de Estrógeno , Estrógenos , Fatiga , Hematócrito , Riñón , Mortalidad , Tamaño de los Órganos , Osteoporosis , Plantas Medicinales , Ratas Endogámicas F344 , Recuento de Reticulocitos , Pruebas de Toxicidad , Urinálisis

RESUMEN

Objective: To establish a novel method based on near-infrared reflectance spectroscopy for fast detection of water and ash in Epimedii Herba, and to investigate moisture and ash content in Epimedii Herba samples from the Chinese markets by near-infrared spectroscopy. Methods: The best calibration model was under the following conditions: standard normal variant and detrending for scatter correction, principal components analysis for cluster analysis, "2, 4, 4, 1" approach for mathematic treatment, and modified partial least square for regression analysis. Results: The proposed calibration model of water and ash based on near-infrared spectroscopy possessed satisfactory precision, accuracy, and stability. Coefficient of determination for calibration and 1 minus variance ratio of water and ash were 0.884 3, 0.800 9, and 0.938 7, 0.851 9, respectively. Correlation coefficient of prediction reached 0.9 and residual predictive deviation exceeded 3.0. The contents of water and ash in Epimedii Herba samples from the Chinese markets were measured by near-infrared spectroscopy for the first time. And 100% and 82% of Epimedii Herba samples meet the criterion in the Chinese Pharmacopoeia. Conclusion: The developed quantitatively analytical method based upon near-infrared spectroscopy is proved to be a rapid, precise, accurate, and non-destructive alternative to the conventional technique. And it shows the great potential in quality control of Epimedii Herba.

RESUMEN

Epimedii Herba is a traditional medicinal herb used in Korea and China and exerts estrogenic activity. In this study, we investigated the effect of peripubertal administration of Epimedii Herba on pubertal development in female rats using a modified protocol of the rodent 20-day pubertal female assay. Female Sprague-Dawley rats (21 days old after weaning, 10 rats per group) were divided into five groups: saline (Con), ethinyl estradiol (E2), Epimedii Herba ext (Ext), icariin (ICI), and icaritin (ICT), which were administered by oral gavage (E2 by subcutaneous injection) from postnatal day (PND) 21 through PND40. The time to vaginal opening (VO) was shorter for the Epimedii groups, particularly for the ICT group (p<0.05). Treatment with ICI and ICT significantly increased the duration of the estrus cycle (ICI, 2.78 days; ICT, 4.0 days; control, 1.78 days). Ovary weight was reduced by E2 treatment and increased by the Ext, ICI, and ICT treatments while the weight of the uterus and pituitary glands increased significantly only in the E2 and ICT groups. Although Epimedii Herba displayed relatively weak estrogenic activity, its repeated administration could affect pubertal development in female rats.