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1.
Chin J Nat Med ; 20(3): 221-228, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35369967

RESUMO

Four new prenylflavonoid glycosides, namely koreanoside H-K (1-4), together with eleven known ones (5-15) were isolated from the leaves of Epimedium koreanum Nakai. Their structures were elucidated by 1D NMR, 2D NMR, HR-ESI-MS, IR and UV. The identification of the sugar moieties was carried out by means of acid hydrolysis and HPLC analysis of their derivatives. It is worth noting that compound 3 and compound 4 were elucidated to contain fucose and quinovose moieties, which were two extremely rare sugar units from the genus Epimedium. The anti-pulmonary fibrosis activity of the new compounds was evaluated using A549 cell line. Compounds 1, 2 and 4 showed significant anti-pulmonary fibrosis activities.


Assuntos
Epimedium , Cromatografia Líquida de Alta Pressão , Epimedium/química , Glicosídeos/química , Glicosídeos/farmacologia , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Folhas de Planta/química
2.
Eur Rev Med Pharmacol Sci ; 26(7): 2478-2488, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-35442463

RESUMO

OBJECTIVE: There are many challenges related to the treatment of coronary atherosclerotic heart disease (CAD). Studies have confirmed that Epimedium extract inhibits myocardial injury induced by myocardial ischaemia, but the mechanism of action remains unclear. This study aimed at analysed the effective components and mechanisms of Epimedium in treating CAD based on network pharmacology and molecular docking studies and to verify the mechanism in vitro. MATERIALS AND METHODS: The TCMSP and UniProt databases were used to filter for the active components and drug targets of Epimedium. The GeneCards database was used to screen disease targets associated with CAD. The intersection of the drug targets of Epimedium and the disease targets of coronary heart disease was studied to identify the targets of Epimedium in the treatment of CAD. Cytoscape software was used to establish and analyse an activity-target network. The STRING database was used to analyse a protein-protein interaction (PPI) network, and proteins in the PPI network were visualized in the R language. Bioconductor software was used for GO function and KEGG pathway enrichment analyses, and visualization analysis was performed in the R language. PyMOL software was used to verify the molecular docking between selected active components of Epimedium and the targets of CAD, and the potential key effective components of Epimedium in the treatment of coronary heart disease were identified. The involvement of the PI3K/Akt pathway was validated by Western blot analysis. RESULTS: (1) Twenty-three active compounds, including Epimedium glycoside, quercetin, luteolin, and olive resin, were screened out. There were 68 common targets of Epimedium and CAD, including IL-6, ESR1, RELA, FOS, NCOA1, CCND1, EGFR, MAPK8, VEGFA, and CASP8. The potential signaling pathways involved in the treatment of CAD by Epimedium included the human cytomegalovirus infection pathway, the PI3K-Akt signaling pathway, the TNF signaling pathway, and the HIF-1 signaling pathway. (2) Luteolin, quercetin, sitosterol, and anhydroicaritin showed strong binding to targets of CAD based on molecular docking studies. (3) Epimedium extract increased the expression of PI3K, Akt and P-Akt but decreased the expression of IL-6  in vitro. CONCLUSIONS: (1) Icariin, quercetin and luteolin may act on target proteins, including IL-6, ESR1, EGFR, MAPK8, VEGFA and CASP8, to participate in the regulation of the human cytomegalovirus infection pathway, the PI3K-Akt signaling pathway, the TNF signaling pathway and other signaling pathways in order to effectively treat CAD. (2) In vitro studies confirmed that Epimedium extract can treat CAD by upregulating PI3K, Akt and P-Akt protein expression and downregulating IL-6 protein expression in SD rat cardiomyocytes.


Assuntos
Doença das Coronárias , Infecções por Citomegalovirus , Medicamentos de Ervas Chinesas , Epimedium , Cardiopatias , Animais , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Epimedium/metabolismo , Receptores ErbB , Interleucina-6 , Luteolina , Simulação de Acoplamento Molecular , Fosfatidilinositol 3-Quinases , Proteínas Proto-Oncogênicas c-akt/metabolismo , Quercetina , Ratos , Ratos Sprague-Dawley
3.
J Microbiol Biotechnol ; 32(4): 437-446, 2022 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-35283431

RESUMO

In this study, to obtain icaritin with high pharmacological activities from icariin, which has a content ratio of over 58% in the total flavonoids of Epimedium herb, a special Epimedium flavonoid-glycosidase was produced, purified and characterized from Aspergillus sp.y848 strain. The optimal enzyme production was gained in a medium containing 5% (w/v) wheat bran extract and 0.7% (w/v) Epimedium leaf powder as the enzyme inducer, and strain culture at 30°C for 6-7 days. The molecular weight of the enzyme was approximately 73.2 kDa; the optimal pH and temperature were 5.0 and 40°C. The enzyme Km and Vmax values for icariin were 15.63 mM and 55.56 mM/h. Moreover, the enzyme hydrolyzed the 7-O-glucosides of icariin into icariside II, and finally hydrolyzed 3-O-rhamnoside of icariside II into icaritin. The enzyme also hydrolyzed 7-O-glucosides of epimedin B to sagittatoside B, and then further hydrolyzed terminal 3-O-xyloside of sagittatoside B to icarisiede II, before finally hydrolyzing 3-O-rhamnoside of icarisiede II into icaritin. The enzyme only hydrolyzed 7-O-glucoside of epimedin A or epimedin C into sagittatoside A or sagittatoside C. It is possible to prepare icaritin from the high-content icariin in Epimedium herb using this enzyme. When 2.5% icariin was reacted at 40°C for 18-20 h by the low-cost crude enzyme, 5.04 g icaritin with 98% purity was obtained from 10 g icariin. Also, the icaritin molar yield was 92.5%. Our results showed icaritin was successfully produced via cost-effective and relatively simple methods from icariin by crude enzyme. Our results should be very useful for the development of medicines from Epimedium herb.


Assuntos
Epimedium , Aspergillus , Epimedium/química , Flavonoides/química , Glucosídeos , Glicosídeo Hidrolases
4.
Aging (Albany NY) ; 14(3): 1562-1588, 2022 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-35165207

RESUMO

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.


Assuntos
Lesões Encefálicas , Epimedium , Fármacos Neuroprotetores , Exposição à Radiação , Envelhecimento , Animais , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Masculino , Fármacos Neuroprotetores/farmacologia , Fármacos Neuroprotetores/uso terapêutico
5.
Sci Rep ; 12(1): 2762, 2022 02 17.
Artigo em Inglês | MEDLINE | ID: mdl-35177764

RESUMO

Herba Epimedii, as a traditional Chinese herb, is divided into large and small flower taxa, and can invigorate sexuality and strengthen muscles and bones. Herba Epimedii is rich in flavonoids, which largely contribute to its medicinal benefits. In our previous studies, we have found that the flavonoids content was much more in small than large flower taxa. To further identify molecular mechanisms of flavonoids metabolism in Herba Epimedii, combined metabolome and transcriptomic analyses were performed to profile leaves and flowers. Association analysis revealed that the expression of genes involved in flavonoid biosynthesis showed significant differences between small and large flower taxa. Eleven flavonols significantly increased in small compared to large flower taxa. Moreover, genes encoding O-methyltransferase played crucial roles in flavonoids metabolism by an integrated analysis. Taken together, these data highlight the breeding tendency of small flower taxa to improve the quality of Herba Epimedii.


Assuntos
Epimedium/metabolismo , Flavonoides/biossíntese , Flores/metabolismo , Perfilação da Expressão Gênica , Metabolômica , Transcriptoma , Epimedium/genética , Flavonoides/genética , Flores/genética
6.
Molecules ; 27(3)2022 Feb 02.
Artigo em Inglês | MEDLINE | ID: mdl-35164291

RESUMO

Alcohol (ethanol) is one of the most common addictive psychoactive substances in the world, and alcoholism may result in harmful effects on human health, especially on the nervous system. Flavonoids are regarded as the main active constituent in Epimedium, which has been used to cure some nervous system diseases such as amnesia for over 1000 years. Here, the protective effects of Epimedium flavonoids against ethanol-induced toxicity in retinoic acid (RA)-treated SH-SY5Y cells were investigated. Their mechanism was explored by a label-free proteomic approach combined with bioinformatic analysis for the first time. The results showed that ethanol treatment decreased cell viability by 18%, whereas the viability increased significantly after intervention with Epimedium flavonoids (p < 0.01). According to proteomic and bioinformatic analyses, hundreds of differentially expressed proteins (DEPs) were identified and classified as biological process (GO_BP), cellular component (GO_CC) and molecular function (GO_MF). Among them, GO_MF of DEPs, especially molecular function relevant to G proteins, greatly changed in SH-SY5Y cells pretreated by Epimedium flavonoids. In the alcoholism pathway, the expression of the Gi protein was up-regulated under the influence of ethanol, whereas Epimedium flavonoids could reverse the expression profile, both of which were validated by Western blot assay. In conclusion, Gi protein seemed to be an important factor in the alcoholism pathway to suppress the ethanol-induced toxicity of SH-SY5Y cells. These findings suggest a protective potential of Epimedium flavonoids against ethanol-induced toxicity to neurons via the regulation of Gi protein function.


Assuntos
Epimedium , Etanol/efeitos adversos , Flavonoides/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Tretinoína/farmacologia , Epimedium/química , Flavonoides/química , Humanos , Neurônios/metabolismo , Fármacos Neuroprotetores/química , Proteoma/metabolismo
7.
J Adv Res ; 36: 175-185, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-35127172

RESUMO

INTRODUCTION: Epimedium L., the largest herbaceous genus of Berberidaceae, is one of the most taxonomically difficult representatives. The classification and phylogenetic relationships within Epimedium are controversial and unresolved. OBJECTIVES: For the first time, we systematically studied the phylogeny and evolution of Epimedium based on plastid genome (plastome) data for better understanding this enigmatic genus. METHODS: We explored the molecular phylogeny, assessed the infrageneric classification, estimated the divergence times, and inferred the ancestral states for flower traits of Epimedium based on 45 plastomes from 32 species. RESULTS: The Epimedium plastome length ranged from 156,635 bp to 159,956 bp. Four types of plastome organization with different inverted repeat boundary changes were identified. Phylogenetic analysis revealed a strong support for the sister relationship of sect. Macroceras and sect. Diphyllon but did not provide a distinct route for petal evolution in sect. Diphyllon. Disharmony between phylogenetic relationships and traditional classification of sect. Diphyllon was observed. Results from divergence time analysis showed that Epimedium diverged in the early Pleistocene (~2.11 Ma, 95% HPD = 1.88-2.35 Ma). Ancestral character state reconstructions indicated transitions from long spur (large-flowered group) to other petal types (small-flowered group) in Epimedium. CONCLUSION: These findings provide new insights into the relationships among Epimedium species and pave the way for better elucidation of the classification and evolution of this genus.


Assuntos
Berberidaceae , Epimedium , Genomas de Plastídeos , Berberidaceae/genética , Epimedium/genética , Flores/genética , Genomas de Plastídeos/genética , Filogenia
8.
Biomed Pharmacother ; 147: 112642, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-35078094

RESUMO

Cardiovascular disease (CVD) is the leading cause of morbidity and mortality among all types of diseases in the world, affecting many millions of individuals every year. CVD includes hypertension, atherosclerosis, pulmonary hypertension, heart failure, cardiomyopathy, coronary heart disease, etc., which are involved in complex etiology, pathogenesis and many risk factors. Modern pharmacological studies have revealed that Epimedium possesses a variety of beneficial effects in regulating cardiovascular inflammation and other biological activities, which provides a therapeutic value for the prevention and treatment of these cardiovascular diseases. In this review, we discuss the cardiovascular protective effects of icariin, an active component from Epimedium, and its metabolites. We summarize a range of studies showing that the modes of action of icariin on CVD relate to its inhibition of myocardial apoptosis and prevention of inflammation on endothelial cell injury, emphasizing the multiple effects of icariin and its metabolites in the repair of common heart failure and myocardial infarction, as well as the formation of neointima. In particular, an emphasis is placed on the discussion of the action mechanism of icariin in combination with new advances in the understanding of the pathology of CVD with potential application of icariin in the treatment of this human disorder.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Epimedium/química , Flavonoides/farmacologia , Compostos Fitoquímicos/farmacologia , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Senescência Celular/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Flavonoides/farmacocinética , Humanos , Mediadores da Inflamação/metabolismo , Músculo Liso Vascular/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Neovascularização Patológica/patologia , Calcificação Vascular/patologia
9.
Food Funct ; 13(2): 904-919, 2022 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-34994765

RESUMO

Chronic renal failure (CRF) is a result of the progression of chronic kidney diseases (CKD), a global health problem with a high cost of treatment and no ideal therapy. The aim of this study is to evaluate the pharmacological efficacy of the total flavonoids in Epimedium koreanum Nakai (TFE), a dietary supplement, against CRF and to determine the mechanism of actions. An adenine-induced CRF rat model and a TGF-ß1 induced human kidney proximal tubule epithelial (HK-2) cell based in vitro renal fibrosis model were established and used to evaluate TFE's efficacy. Renal hemodynamics, biochemical indexes, inflammatory cytokines, histopathology and the reactive oxygen species (ROS) levels were determined to evaluate the efficacy of TFE on CRF. NMR-based metabolomics, immunohistochemical (IHC) staining, immunofluorescence (IF) staining, quantitative real time-PCR (qRT-PCR) and western blotting were conducted to determine the mechanism. The results showed that TFE had a significant effect on CRF at 150 mg kg-1 d-1 and could significantly alleviate renal fibrosis in the animal model. Twelve potential biomarkers, which mainly involve energy metabolism pathways, for CRF were identified using the metabolomics approach. The mechanism study suggested that TFE regulated AMP-activated protein kinase (AMPK)/acetyl-CoA carboxylase (ACC) and AMPK/silent information regulator 1 (SIRT1)/nuclear factor kappa-B (NF-κB) signaling pathways. Furthermore, the effect of TFE was inhibited by compound C in the in vitro experiment, which also confirmed the above conclusion.


Assuntos
Epimedium/química , Flavonoides/farmacologia , Extratos Vegetais/farmacologia , Insuficiência Renal Crônica/tratamento farmacológico , Adenina/toxicidade , Animais , Biomarcadores , Peso Corporal , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Humanos , Testes de Função Renal , Masculino , Extratos Vegetais/química , Folhas de Planta/química , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo
10.
Cell Death Dis ; 13(1): 69, 2022 01 20.
Artigo em Inglês | MEDLINE | ID: mdl-35058429

RESUMO

Oxidative stress (OS) is one of the primary factors leading to male infertility. Oral administration of antioxidants has thus far been found to significantly improve the quality of human sperm. Therefore, antioxidant treatment has become the consensus among international experts on male infertility. In this study, peroxisomal biogenesis factor 3 (Pex3)-knockout (KO, -/-) mice were used as a model to compare the efficacy of three types of traditional Chinese medicine (TCM) granules (Epimedium [YYH], Cuscuta [TSZ], and Rhodiola [HJT]) for male reproductive function rescue. YYH was revealed to be the best and exerted a rescue effect on Pex3-/- mice with spermatogenesis defects. In addition, YYH prominently reduced ROS levels in the testes, inhibited DNA oxidative damage in spermatogenic cells, promoted the proliferation of spermatogenic cells, and inhibited apoptosis in Pex3-/- male mice. Furthermore, the mechanism by which YYH ameliorated dyszoospermia was confirmed via the establishment of cyclin-dependent kinase inhibitor 2 A (P16Ink4a)-KO mice. Specifically, Pex3-/- mice produced elevated amounts of ROS, which damaged germ cell DNA and further activated the signaling pathway of the cell senescence regulatory protein P16-CDK6, resulting in cell cycle arrest and eventually contributing to spermatogenesis dysfunction. YYH supplementation partially corrected the associated phenotype in gene KO mice by affecting P16 expression levels, thus improving the reproductive outcome to a certain extent.


Assuntos
Epimedium , Infertilidade Masculina , Animais , Antioxidantes/farmacologia , Infertilidade Masculina/genética , Masculino , Camundongos , Camundongos Knockout , Espécies Reativas de Oxigênio , Espermatogênese/genética
11.
Biomed Pharmacother ; 146: 112581, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34965505

RESUMO

Epimedium koreanum Nakai (EKN) is a popular plant in Korean and Chinese medicine for treating a variety of ailments. The aqueous extract of EKN has a significant inhibitory impact on influenza A virus (IAV) infection by directly blocking viral attachment and having a virucidal effect, according to this study. Using fluorescent microscopy and fluorescence-activated cell sorting (FACS) with a green fluorescent protein (GFP)-tagged Influenza A/PR/8/34 virus, we examined the effect of EKN on viral infection. By viral infection, EKN strongly suppresses GFP expression, and at a dosage of 100 µg/mL, EKN decreased GFP expression by up to 90% of the untreated infected control. Immunofluorescence and Western blot analyses against influenza viral proteins revealed that EKN decreased influenza viral protein expression in a dose-dependent manner. EKN inhibited the H1N1 influenza virus's hemagglutinin (HA) and neuraminidase (NA), preventing viral attachment to cells. Furthermore, EKN had a virucidal impact and inhibited the cytopathic effects of H1N1, H3N2 and influenza B virus infection. Finally, our findings show that EKN has the potential to be developed as a natural viral inhibitor against influenza virus infection.


Assuntos
Antivirais/farmacologia , Epimedium , Influenzavirus A/efeitos dos fármacos , Extratos Vegetais/farmacologia , Animais , Hemaglutininas/efeitos dos fármacos , Humanos , Camundongos , Neuraminidase/efeitos dos fármacos , Proteínas Virais/efeitos dos fármacos , Ligação Viral/efeitos dos fármacos
12.
Phytomedicine ; 96: 153834, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34952294

RESUMO

BACKGROUND: Non-small cell lung cancer (NSCLC) is a major subtype of lung cancer with a higher mortality rate. Both apoptosis and autophagy are crucial processes in the pathophysiology of NSCLC. Muyin extract (MSE) is a combination of Momordica cochinchinensis (Lour.) Spreng seeds and Epimedium brevicornu Maxim extract, with an optimal ratio of 1:1. Our previous research has firstly shown that MSE exerts a good anti-tumor activity, especially for NSCLC. PURPOSE: This study aims to evaluate the inhibitory effect of MSE on NSCLC and explore the underlying mechanism. METHODS: In vitro, cell proliferation was examined by MTT and colony formation. Apoptosis was detected by annexin V-FITC/PI assay while autophagy was assessed by Acridine orange (AO) and Monodansylcadaverine (MDC) staining. In vivo, Lewis lung cancer cell transplanted mice model was established to measure the effect of MSE on tumor growth. Hematoxylin eosin (H & E) staining was used to observe the pathological changes of the tumor after MSE treatment. The apoptosis in tumor tissue was detected by TUNEL assay. Meanwhile, the cellular proliferation marker Ki67 and autophagy marker LC3Ⅱ were observed by immunohistochemistry staining. The IL-4 and IFN-γ concentrations in blood were tested by Elisa. The apoptosis related factors (Bcl-2, Bax Caspase-3, cleaved Caspase-3, Caspase-9 and p53), autophagy marker proteins (Atg-5, Becline-1, LC3Ⅱ/Ⅰand p62) as well as Akt/mTOR pathway were detected by western blotting. RESULTS: Present study showed that MSE greatly inhibited the proliferation of NSCLC in vitro and in vivo, together with apoptotic rate increasing. P53 and cleaved Caspase-3 levels were up-regulated while Bcl-2/Bax ratio, Caspase-3 and Caspase-9 levels were significantly down-regulated treated with MSE. Meanwhile, MSE activated autophagy, Atg-5, Becline-1 as well as the ratio of LC3Ⅱ/Ⅰ were notably up-regulated while p62 was down-regulated after MSE treatment. Importantly, MSE significantly blocked Akt/mTOR pathway, which is a common upstream signal triggered by autophagy and apoptosis. Furthermore, when co-treated with specific autophagy inhibitor, the inhibitory rate and anti-apoptotic Bcl-2 level were significantly reversed. Impressively, MSE remarkably increased IFN-γ/ IL-4 ratio while VP16 did not in animal model, and the inhibition rate in tumor weight after MSE treatment was higher than xiaojin pill. CONCLUSION: Taken together, it is proved that MSE may be a promising oral TCM candidate for NSCLC therapy with immunity improvement. The underlying mechanisms could be associated with the induction of apoptosis and autophagy through blocking Akt/mTOR pathway, meanwhile, it may promote crosstalk between autophagy and apoptosis.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Animais , Apoptose , Autofagia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Linhagem Celular Tumoral , Epimedium/química , Neoplasias Pulmonares/tratamento farmacológico , Camundongos , Momordica/química , Extratos Vegetais/farmacologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais
13.
Zhongguo Zhong Yao Za Zhi ; 46(22): 5825-5831, 2021 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-34951171

RESUMO

This study evaluated the effects of epimedium polysaccharide(EPS) on the solubility of icariin and baohuoside Ⅰ so as to preliminary explore its solubilization function and the underlying mechanism. The solubility of these two insoluble flavonoids in water and polysaccharide solutions was compared by high performance liquid chromatography, and the mechanism was investigated by diffe-rential scanning calorimetry(DSC) and critical micelle concentration determination. The results indicated that their solubilization in crude EPS solutions was concentration-dependent. The solubility of icariin and baohuoside Ⅰ in 20 mg·mL~(-1) EPS-1-1 was 9.05 times and 5.76 times that in water, respectively; while their solubility in 20 mg·mL~(-1) EPS-2-1 was 10.55 and 8.39 times that in water, respectively. The change of the DSC thermograms suggested the formation of new complexes from icariin and baohuoside Ⅰ with polysaccharides. The critical micelle concentrations proved the micellar properties of both EPS-1-1 and EPS-2-1. In short, EPS can significantly increase the solubility of icariin and baohuoside Ⅰ, the mechanism of which may be related to the formation of micellar complexes between EPS and insoluble flavonoids.


Assuntos
Epimedium , Flavonoides , Polissacarídeos , Solubilidade
14.
Chem Biodivers ; 18(12): e2100741, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34786854

RESUMO

Three new hydroxyphenylacetic acid derivatives, stachylines E-G (1-3), and a new alkaloid, mortieridinone (4), along with six known compounds (5-10), were isolated from endophytic fungus Mortierella sp. in Epimedium acuminatum Franch. Their structures were determined by their spectroscopic analyses and by comparison with the literature data. Compounds 7 and 10 showed selective antibacterial activity against tested multidrug-resistant bacteria with minimum inhibitory concentration (MIC) values ranging from 25 to 3.13 µg/mL.


Assuntos
Alcaloides/farmacologia , Antibacterianos/farmacologia , Epimedium/microbiologia , Mortierella/química , Fenilacetatos/farmacologia , Alcaloides/química , Alcaloides/isolamento & purificação , Antibacterianos/química , Antibacterianos/isolamento & purificação , Farmacorresistência Bacteriana Múltipla/efeitos dos fármacos , Enterococcus faecium/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Fenilacetatos/química , Fenilacetatos/isolamento & purificação , Staphylococcus aureus/efeitos dos fármacos
16.
J Med Chem ; 64(20): 14942-14954, 2021 10 28.
Artigo em Inglês | MEDLINE | ID: mdl-34644502

RESUMO

Icaritin is an active ingredient in Epimedium, which has a variety of pharmacological activities. However, the low activity of Icaritin and the unclear target greatly limit its application. Therefore, based on the structure of Icaritin, we adopted the strategy of replacing toxic groups and introducing active groups to design and synthesize a series of new analogues. The top compound C3 exhibited better antimultiple myeloma activity with an IC50 of 1.09 µM for RPMI 8226 cells, induced RPMI 8226 apoptosis, and blocked the cell cycle in the S phase. Importantly, transcriptome analysis, cellular thermal shift assay, and microscale thermophoresis assay confirmed that DEPTOR was the target of C3. Moreover, we explored its binding mode with C3. Especially, C3 displayed satisfactory inhibition of tumor growth in RPMI 8226 xenografts without obvious side effects. In summary, C3 was discovered as a novel putative inhibitor of DEPTOR for the treatment of multiple myeloma.


Assuntos
Antineoplásicos/farmacologia , Desenho de Fármacos , Flavonoides/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Mieloma Múltiplo/tratamento farmacológico , Antineoplásicos/síntese química , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Ensaios de Seleção de Medicamentos Antitumorais , Epimedium/química , Flavonoides/síntese química , Flavonoides/química , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Estrutura Molecular , Mieloma Múltiplo/metabolismo , Relação Estrutura-Atividade
17.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 29(5): 1548-1554, 2021 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-34627438

RESUMO

OBJECTIVE: To observe the effects of Epimedium polysaccharides (EPS) on bone marrow hematopoietic function and Th17/Treg balance in aplastic anemia (AA) mice, and preliminarily explore its therapeutic mechanism. METHODS: Forty BALB/C mice were randomly divided into control (control), model (model), stanozolol (stanozolol) and epimedium polysaccharide (EPS) group, with 10 mice in each group. Except for the control group, Acetophenazine, Gy irradiation and cyclophosphamide triple application were used to establish AA models for the other groups. After the model was established, the stanozolol group was intragastrically administered with 4 mg/kg stanozolol suspension, the EPS group was intragastrically administered with 100 mg/kg epimedium polysaccharide, while the control group and the model group were given an equal volume of 0.9% sodium chloride solution by gavage once a day, for 14 consecutive days. The automatic animal blood analyzer was used to detect the changes in peripheral blood hemoglobin (Hb), red blood cells (RBC), white blood cells (WBC) and platelets (PLT), flow cytometry was used to detect the proportion of Treg and Th17 cells, the levels of interleukin 2 (IL-2), interleukin 11 (IL-11) and tumor necrosis factor α (TNF-α) were detected by ELISA, the number of nucleated bone marrow cells was counted, HE staining and immunohistochemical staining were used to detect the number, the proliferation and apoptosis of bone marrow cells, Western blot was used to detect the expression of signal transducer and activator of transcription 3 (STAT3), retinoic acid receptor-related orphan receptor γ (RORγt), transducer and activator of transcription 5 (STAT5) and fork head transcription factor 3 (Foxp3). RESULTS: Compared with the model group, the levels of Hb, RBC, WBC and PLT in the peripheral blood of mice in stanozolol and EPS group significantly increased, the proportion of Th17 cells was significantly reduced, and the proportion of Treg cells significantly increased. The levels of IL-2 and TNF-α in serum were significantly reduced (P<0.05), the level of IL-11 significantly increased (P<0.05), the number of bone marrow nucleated cells significantly increased (P<0.05), the positive rate of Ki-67 significantly increased (P<0.05) and the positive rate of Caspase-3 was significantly reduced (P<0.05). At the same time, the protein expression of STAT3 and RORγt significantly decreased, and the protein expression of STAT5 and Foxp3 increased, the difference showed statistically significant (P<0.05). CONCLUSION: EPS can promote the recovery of bone marrow hematopoietic function in AA mice and improve Th17/Treg imbalance, the mechanism may be related to the inhibition of STAT3/RORγt expression and promotion of STAT5/Foxp3 expression.


Assuntos
Anemia Aplástica , Epimedium , Animais , Medula Óssea , Camundongos , Camundongos Endogâmicos BALB C , Polissacarídeos , Linfócitos T Reguladores , Células Th17
18.
Int Immunopharmacol ; 101(Pt A): 108181, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34607229

RESUMO

Demyelinating diseases of the central nervous system are characterized by recurrent demyelination and progressive neurodegeneration, but there are no clinical drugs targeting myelin regeneration or improving functional disability in the treatment of multiple sclerosis. Total flavone of Epimedium (TFE) is the main active components of Epimedium, which exhibits the beneficial biological activities in the treatment of diseases, but there is no report in the treatment of demyelinating disorder. The purpose of this study was to explore the therapeutic potential and possible mechanism of TFE in the treatment of demyelination. The results showed that TFE efficiently improved the behavioural performance and histological demyelination in cuprizone (CPZ)-induced demyelinating model. In terms of action, TFE increased astrocytes enrichment in corpus callosum, striatum and cortex, and promoted astrocytes to express neurotrophic factors. Furthermore, the expression of platelet-activating factor receptor (PAFR) in astrocytes was induced by CPZ feeding and LPS stimulation, accompanied by the increase of inflammatory cytokines TNF-α,IL-6 and IL-1ß. TFE declined the expression of PAFR, and inhibited inflammatory response. At the same time, TFE also antagonized PAFR activation and inflammatory response triggered by PAF, which further confirmed that TFE, as a new PAFR antagonist, inhibited the astrocyte-derived inflammatory response by antagonizing PAFR-neuroinflammation axis, thus contributing to myelin protection and regeneration.


Assuntos
Doenças Desmielinizantes/tratamento farmacológico , Epimedium/química , Extratos Vegetais/farmacologia , Glicoproteínas da Membrana de Plaquetas/antagonistas & inibidores , Receptores Acoplados a Proteínas G/antagonistas & inibidores , Administração Oral , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/imunologia , Astrócitos/metabolismo , Cuprizona/administração & dosagem , Cuprizona/toxicidade , Doenças Desmielinizantes/induzido quimicamente , Doenças Desmielinizantes/imunologia , Doenças Desmielinizantes/patologia , Modelos Animais de Doenças , Flavonas/farmacologia , Flavonas/uso terapêutico , Humanos , Masculino , Camundongos , Bainha de Mielina/efeitos dos fármacos , Bainha de Mielina/imunologia , Bainha de Mielina/patologia , /imunologia , Extratos Vegetais/uso terapêutico
19.
Phytomedicine ; 91: 153680, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34352588

RESUMO

BACKGROUND: Fragility fractures due to menopausal osteoporosis are a major cause of morbidity and mortality. Osteoporotic medications have substantial side effects that limit long term use. HYPOTHESES: Ingestion of a purified extract of Epimedium spp. (EP) is safe, can increase serum levels of prenylflavonoid metabolites, exert positive changes in bone specific alkaline phosphatase (BSAP), suppress of tumor necrosis factor receptor associated factor 6 (TRAF6) protein in osteoclast-precursor monocytes in peripheral blood and therefore have the potential to reduce post-menopausal bone loss. STUDY DESIGN & METHODS: Healthy postmenopausal women were randomized in a double-blind fashion to consume either EP prenylflavonoid extract (740 mg daily) or placebo daily for 6 weeks. The main outcome measures were safety and pharmacokinetics of EP flavonoids. Fasting blood was collected at 3- and 6-weeks, and two weeks after stopping medication for safety evaluations and measurement of BSAP. Peripheral blood monocytes were harvested for measurement of TRAF6 levels. Serum levels of the EP metabolites icariin, icariside I & II, icaritin and desmethylicaritin were measured using tandem mass spectrometry, and non-compartmental pharmacokinetic analyses performed using WinNonlin software. RESULTS: Between October 2018 and Jun 2020, 58 postmenopausal women, aged 57.9 ± 8.9 years, were randomized and completed the study. Consumption of EP prenylflavonoids was not associated with any significant adverse symptoms, with no changes in hepatic, hematological, and renal parameters observed. The main metabolites detected in sera after ingestion of EP prenylflavonoid capsules were desmethylicaritin, icaritin and icariside II. Icariin and icariside I were below detection levels. Ingestion of EP prenylflavonoids induced a median Cmax and AUC0→∞ for desmethylicaritin of 60.9 nM, and 157.9 nM ×day, respectively; and were associated with higher levels of BSAP (p < 0.05) and a trend (p = 0.068) towards lower levels of TRAF6 in peripheral blood monocytes eight weeks after commencing prenylflavonoid ingestion. Prenylflavonoid metabolites were not detected in the sera of placebo participants. CONCLUSIONS: Despite the widespread consumption of EP extracts, the safety, mechanisms of action of their bioactive compounds, and therapeutic indications in humans are unknown. Daily consumption of EP prenylflavonoids for six weeks was safe. The predominant metabolite in sera was desmethylicaritin. Rise in prenylflavonoid metabolites was associated with higher levels of the bone anabolic marker BSAP, suggesting potential therapeutic value for post-menopausal osteoporosis.


Assuntos
Fosfatase Alcalina/metabolismo , Epimedium , Flavonoides/uso terapêutico , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Osteoporose Pós-Menopausa , Extratos Vegetais/uso terapêutico , Idoso , Densidade Óssea , Método Duplo-Cego , Epimedium/química , Flavonoides/farmacocinética , Humanos , Pessoa de Meia-Idade , Osteoclastos , Osteoporose Pós-Menopausa/tratamento farmacológico , Extratos Vegetais/farmacocinética , Pós-Menopausa , Fator 6 Associado a Receptor de TNF
20.
Molecules ; 26(12)2021 Jun 11.
Artigo em Inglês | MEDLINE | ID: mdl-34208231

RESUMO

Phytochemical investigation on the n-BuOH-soluble fraction of the aerial parts of Epimedium koreanum using the PCSK9 mRNA monitoring assay led to the identification of four previously undescribed acylated flavonoid glycosides and 18 known compounds. The structures of new compounds were elucidated by NMR, MS, and other chemical methods. All isolated compounds were tested for their inhibitory activity against PCSK9 mRNA expression in HepG2 cells. Of the isolates, compounds 6, 7, 10, 15, and 17-22 were found to significantly inhibit PCSK9 mRNA expression. In particular, compound 7 was shown to increase LDLR mRNA expression. Thus, compound 7 may potentially increase LDL uptake and lower cholesterol levels in the blood.


Assuntos
Epimedium/química , Flavonoides/química , Glicosídeos/química , RNA Mensageiro/antagonistas & inibidores , Linhagem Celular Tumoral , Epimedium/metabolismo , Flavonoides/metabolismo , Flavonoides/farmacologia , Glicosídeos/metabolismo , Glicosídeos/farmacologia , Humanos , Componentes Aéreos da Planta/química , Componentes Aéreos da Planta/metabolismo , Prenilação , Pró-Proteína Convertase 9/metabolismo , Receptores de LDL/agonistas
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