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1.
Ecotoxicol Environ Saf ; 205: 111342, 2020 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-32971455

RESUMO

Radix aconiti lateralis (Fuzi) is widely used in China as a traditional Chinese medicine for the treatment of asthenia, pain and inflammation. However, its toxic alkaloids often lead to adverse reactions. Currently, most of the toxicity studies on Fuzi are focused on the heart and nervous system, and more comprehensive toxicity studies are needed. In this study, based on the previous reports of Fuzi hepatotoxicity, serum pharmacochemistry and network toxicology were used to screen the potential toxic components of Heishunpian(HSP), a processed product of Fuzi, and to explore the possible mechanism of HSP-induced hepatotoxicity. The results obtained are expressed based on the toxicological evidence chain (TEC). It was found that 22 potential toxic components screened can affect Th17 cell differentiation, Jak-STAT signaling pathway, glutathione metabolism, and other related pathways by regulating AKT1, IL2, F2, GSR, EGFR and other related targets, which induces oxidative stress, metabolic disorders, cell apoptosis, immune response, and excessive release of inflammatory factors, eventually inducing liver damage in rats. This is the first study on HSP-induced hepatotoxicity based on the TEC concept, providing references for further studies on the toxicity mechanism of Fuzi.


Assuntos
Aconitum/química , Alcaloides/toxicidade , Doença Hepática Induzida por Substâncias e Drogas/patologia , Medicamentos de Ervas Chinesas/toxicidade , Modelos Biológicos , Alcaloides/sangue , Alcaloides/isolamento & purificação , Animais , Apoptose/efeitos dos fármacos , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , China , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacocinética , Masculino , Medicina Tradicional Chinesa , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar
2.
Environ Toxicol ; 35(10): 1043-1049, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32415908

RESUMO

In this study, we used ICI 182 780 (ICI), an estrogen receptor (ER) antagonist, to investigate the estrogenic activity of Danshen, and to further explored whether Danshen extract can block Leu27IGF-II-induced hypertrophy in H9c2 cardiomyoblast cells. We first used an IGF-II analog Leu27IGF-II, which specifically activates IGF2R signaling cascades and induces H9c2 cardiomyoblast cell hypertrophy. However, Danshen extract completely inhibited Leu27IGF-II-induced cell size increase, ANP and BNP hypertrophic marker expression, and IGF2R induction. We also observed that Danshen extract inhibited calcineurin protein expression and NFAT3 nuclear translocation, leading to suppression of Leu27IGF-II-induced cardiac hypertrophy. Moreover, the anti-Leu27IGF-II-IGF2R signaling effect of Danshen was totally reversed by ICI, which suggest the cardio protective effect of Danshen is mediated through estrogen receptors. Our study suggests that, Danshen exerts estrogenic activity, and thus, it could be used as a selective ER modulator in IGFIIR induced hypertrophy model.


Assuntos
Crescimento Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Fator de Crescimento Insulin-Like II/análogos & derivados , Mioblastos Cardíacos/efeitos dos fármacos , Receptor IGF Tipo 2/metabolismo , Salvia miltiorrhiza/química , Animais , Calcineurina/metabolismo , Cardiomegalia/prevenção & controle , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/isolamento & purificação , Antagonistas do Receptor de Estrogênio/farmacologia , Fulvestranto/farmacologia , Fator de Crescimento Insulin-Like II/farmacologia , Mioblastos Cardíacos/metabolismo , Mioblastos Cardíacos/patologia , Transporte Proteico , Ratos , Receptores Estrogênicos/metabolismo , Transdução de Sinais
3.
J Pharmacol Sci ; 143(3): 165-175, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32387002

RESUMO

yeyachun and danshen exist as Chinese patent medicine, Xuemai Tong, and are clearly effective at alleviating liver fibrosis (LF). Previous studies have indicated that triterpenoids from yeyachun (EFT), and phenolic acids from danshen (SMP) are effective in the treatment of LF. The regulation of intestinal flora is an effective method for treating LF. The aim of this study was to investigate the effect of a mixture of EFT and SMP on carbon tetrachloride (CCl4) induced LF. Our results showed the mixture significantly decreased liver damage and fibrosis index, and maintained liver tissue composition, compared to the model group. Moreover, the imbalance of symptoms of intestinal flora was improved. The mixture also caused changes to metabolites of gut flora. Furthermore, the expression of CD68 in liver tissues from the treated groups was significantly decreased when compared to the model group. However, no significant difference was observed from microstructure of gut tissues and LPS concentrations in the serum between mixture treated mice and model mice. This study suggests that the mixture of EFT and SMP had a significant effect on CCl4 induced LF, and the mechanism of this action, at least in part, involved the regulation of intestinal flora and their metabolites.


Assuntos
Tetracloreto de Carbono/efeitos adversos , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Microbioma Gastrointestinal/efeitos dos fármacos , Hidroxibenzoatos/farmacologia , Hidroxibenzoatos/uso terapêutico , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/microbiologia , Fitoterapia , Salvia miltiorrhiza/química , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Animais , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/metabolismo , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/isolamento & purificação , Fígado/metabolismo , Cirrose Hepática/induzido quimicamente , Cirrose Hepática/metabolismo , Masculino , Camundongos Endogâmicos ICR , Triterpenos/isolamento & purificação
4.
Psychopharmacology (Berl) ; 237(7): 2111-2124, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32363440

RESUMO

INTRODUCTION: Gelsemine is a natural alkaloid extracted from Gelsemium elegans Benth., a traditional Chinese medicinal herb. Gelsemine has been shown to penetrate the brain, and could produce neurological activities, such as anxiolytic and neuralgia-alleviating effects, suggesting that this natural compound might be used for treating nervous system diseases. RESULTS: In this study, we have found, for the first time, that gelsemine at low concentrations (5-10 µg/kg) significantly alleviated cognitive impairments induced by ß-amyloid (Aß) oligomer, a main neurotoxin of Alzheimer's disease (AD). In addition, gelsemine substantially prevented Aß oligomer-induced over-activation of microglia and astrocytes, indicating that gelsemine might reduce AD-related gliosis. Consistently, gelsemine inhibited the over-expression of pro-inflammatory cytokines, including interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α), in the brain of mice. Moreover, gelsemine largely increased the expression of pSer9-glycogen synthase kinase-3ß (GSK3ß), and decreased the hyper-phosphorylation of tau protein as evidenced by Western blotting analysis. Furthermore, gelsemine prevented Aß oligomer-induced reduction of PSD-95, a representative post-synaptic protein. CONCLUSION: All these results directly demonstrated the anti-Aß oligomer neuroprotective properties of gelsemine, opening a novel perspective for the development of gelsemine-based therapeutics against Aß-associated neurodegeneration disorders, including AD in particular.


Assuntos
Alcaloides/uso terapêutico , Peptídeos beta-Amiloides/toxicidade , Disfunção Cognitiva/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Gelsemium , Mediadores da Inflamação/antagonistas & inibidores , Fragmentos de Peptídeos/toxicidade , Alcaloides/isolamento & purificação , Alcaloides/farmacologia , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Mediadores da Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR
5.
Med Sci Monit ; 26: e918520, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892693

RESUMO

BACKGROUND Compound Kushen injection (CKI) is a traditional Chinese medicine preparation for clinical treatment of cancer pain or treatment of various types of solid tumors. The purpose of this study was to identify the main active compounds from CKI and to investigate its anti-cancer mechanisms via drug target biological network pharmacology construction and prediction. MATERIAL AND METHODS Constituents of CKI were retrieved from Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. Disease targets were collected in the Human Gene (Gene Cards) and Human Mendelian Inheritance (OMIM) databases. "Ingredients-protein targets-pathway" networks were constructed using Cytoscape. STRING database platform to construct enrichment of protein-protein interactions (PPI), related diseases and pathways network. Gene Ontology (GO) biological functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway of were performed to investigate by using Bioconductor tool for analysis. RESULTS The results indicated that 60 constituents of absorption, distribution, metabolism, and excretion (ADME) filtration resulted in 33 constituents exhibiting significant correlations with anti-cancer and CKI may target 113 proteins, including IL6, EGFR, CASP3, VEGFA, MYC, and ESR1. GO and KEGG enrichment analysis results show that 129 biological processes and 93 signal pathways associated with cancer. It mainly involves cancers such as prostate cancer, bladder cancer, hepatocellular carcinoma, colorectal cancer, breast cancer, etc. Active ingredients might also induce apoptosis in cancer cells via the p53 and PI3K-Akt signaling pathway mechanism. CONCLUSIONS This study was based on pharmacological networks results for the prediction of the multi-constituent, multi-target, and multi-pathway mechanisms of CKI, which might be a promising potential therapeutic and prevention candidate for anti-cancer. However, based on computer data mining and analysis, this study still needs to be further verified by in vivo/in vitro experiments, and the safety of CKI needs to be evaluated.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Neoplasias/tratamento farmacológico , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , China , Biologia Computacional/métodos , Medicamentos de Ervas Chinesas/isolamento & purificação , Humanos , Medicina Tradicional Chinesa/métodos , Neoplasias/metabolismo , Mapeamento de Interação de Proteínas/métodos , Mapas de Interação de Proteínas/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos
6.
J Chromatogr A ; 1609: 460480, 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31530382

RESUMO

A semi-automated online platform was established successfully for preliminary screening of potential active flavonoids of traditional Chinese medicines (TCMs) in multicomponent system. Online coupling of the in vitro intestinal absorption model, solid phase extraction (SPE) and high-performance liquid chromatography (HPLC) was actualized at the first time. The Ussing chamber model was selected to absorb the constituents of TCMs. A mini chromatographic column filled with C18 was used as a SPE column for online enrichment of flavonoids. HPLC was applied to analyze the constituents screened by platform. With the use of rutin as a model flavonoid, the specifications of SPE column, eluting solvent, elution time and flow rate of eluent were systematically investigated to optimize online system. Under the optimal conditions, the linear range of rutin was 0.125-368 µg/mL with the correlation coefficient (R2) greater than 0.9947. The limit of detection (LOD) was as low as 0.0500 µg/mL and the limit of quantification (LOQ) was 0.125 µg/mL. The intra-day relative standard deviation (RSD) and inter-day RSD was 2.5% and 3.8%, respectively. The recoveries of rutin in the intestinal absorption samples ranged from 93.2% to 94.0%. Finally, the online system was applied to screen the potential active flavonoids of Scutellaria baicalensis Georgi (Huangqin, HQ) and Polygoni Cuspidati Rhizoma et Radix (Huzhang, HZ). A total of 14 flavonoids of these two TCMs were identified by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS), and 12 flavonoids of them were screened as the potential active components by online Ussing chamber-SPE-HPLC. In comparison with offline method and gavage in rats, the online system can screen the active constituents from TCMs more accurately and completely. The results demonstrated that the online system was reliable and sufficiently accurate for screening and determination of the potential active flavonoids of TCMs in multicomponent system.


Assuntos
Automação/métodos , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Fallopia japonica/química , Scutellaria baicalensis/química , Extração em Fase Sólida/métodos , Animais , Flavonoides/química , Flavonoides/isolamento & purificação , Limite de Detecção , Medicina Tradicional Chinesa , Raízes de Plantas/química , Ratos , Rizoma/química , Espectrometria de Massas em Tandem/métodos
7.
J Pharm Biomed Anal ; 177: 112837, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31493746

RESUMO

The ambiguity of dose-effect relationship of many traditional Chinese medicines (TCMs) has always influenced their rational use in TCM clinic. Rhubarb, a preferred representative of cathartic TCM, is currently widely used that results in a diversity of its dosage. The aim of this study was to use an integrated metabolomics strategy to simultaneously reveal dose-effect relationship and therapeutic mechanisms of different efficacy of rhubarb in constipation rats. Six doses of rhubarb (0.135, 0.27, 0.81, 1.35, 4.05, and 8.1 g/kg) were examined to elucidate the laxative and fire-purging effects by pathological sections and UPLC-Q-TOF/MSE. The results showed that there existed serious lesions in the stomach and colon of model rats. And conditions were basically improved to some extent in rhubarb-treated groups. Through relative distance calculation based on metabolomics score plots, it suggested that the effective dose threshold (EC20-EC80 range) of rhubarb was from 0.31 to 4.5 g/kg (corresponding to 3.44-50.00 g in the clinic) in rat serum and 0.29-2.1 g/kg (corresponding to 3.22-23.33 g in the clinic) in feces. Then, 33 potential biomarkers were identified in total. Functional pathway analysis revealed that the alterations of these biomarkers were associated with 15 metabolic pathways, mainly including arachidonic acid metabolism, glycerophospholipid metabolism, steroid biosynthesis, primary bile acid biosynthesis and sphingolipid metabolism. Of note, different doses of rhubarb could alleviate endogenous disorders to varying degrees through regulating multiple perturbed pathways to the normal state, which might be in a dose-dependent manner and involved in therapeutic mechanisms. To sum up, integrated serum and fecal metabolomics obtained that rhubarb ranging from 0.31 to 2.1 g/kg is safe and effective for constipation treatment. Also, our findings showed that the robust metabolomics techniques would be promising to be more accurately used in the dose-effect studies of complex TCM, and to clarify syndrome pathogenesis and action mechanisms in Chinese medicine.


Assuntos
Constipação Intestinal/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Laxantes/administração & dosagem , Redes e Vias Metabólicas/efeitos dos fármacos , Rheum/química , Animais , Ácido Araquidônico/análise , Ácido Araquidônico/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Cromatografia Líquida de Alta Pressão/métodos , Constipação Intestinal/sangue , Constipação Intestinal/metabolismo , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/isolamento & purificação , Fezes/química , Glicerofosfolipídeos/análise , Glicerofosfolipídeos/metabolismo , Humanos , Laxantes/isolamento & purificação , Masculino , Metaboloma/efeitos dos fármacos , Metabolômica/métodos , Ratos
8.
J Ethnopharmacol ; 247: 112223, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31553926

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Arecae semen has been used as vermifuge and digestant in traditional Chinese medicine (TCM) for more than one thousand years. However, the toxicity effect of areca semen and its underlying mechanism are still unclear. THE AIM OF THE STUDY: This study was aimed to investigate the toxicity of arecae semen and to explore its mechanisms by serum metabolomics. MATERIALS AND METHODS: The male Wistar rats were divided into the control group and treated group (n = 6 in each group), which were given by gavage with distill water or arecae semen aqueous extract (ASAE) once a day for 30 days, respectively. Serum samples were collected from all the rats after treatment of 7-day, 14-day and 30-day for metabolomics analysis. Moreover, biochemistry analysis and histopathological examination were performed at the end of study. RESULTS: The phenomenon of diarrhea, less physical activity, tremors and body curl up were observed in the treated group. Additionally, the body weights of treated rats were significantly decreased compared with control rats from the 8th day after oral administration. Except the level of creatinekinase (CK) in the treated group significantly increased compared with the control group, there were no differences on biochemistry parameters and histopathological test in the two groups. Combined with the methods of principal component analysis (PCA), orthogonal projection to latent structure-discrimination analysis (OPLS-DA) and available databases, the treated and control rats were clearly distinguished from each other and 19 metabolites were identified as the potential biomarkers in the arecae semen treated rats. The identified biomarkers indicated that there were perturbations of the phospholipid metabolism, amino acid metabolism and fat acid metabolism in the treated group. CONCLUSIONS: This indicated that arecae semen possessed certain cardiotoxicity and inhibited the normal growth in Wistar male rats. In addition, the metabolomics approach is a useful tool to study the toxicity in TCM.


Assuntos
Areca/química , Cardiotoxicidade/etiologia , Medicamentos de Ervas Chinesas/toxicidade , Crescimento e Desenvolvimento/efeitos dos fármacos , Metaboloma/efeitos dos fármacos , Administração Oral , Aminoácidos/metabolismo , Animais , Anti-Helmínticos/administração & dosagem , Anti-Helmínticos/isolamento & purificação , Anti-Helmínticos/toxicidade , Biomarcadores/sangue , Biomarcadores/metabolismo , Cardiotoxicidade/sangue , Cardiotoxicidade/diagnóstico , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/isolamento & purificação , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/isolamento & purificação , Fármacos Gastrointestinais/toxicidade , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Metabolômica , Ratos , Ratos Wistar , Sementes/química , Testes de Toxicidade , Água/química
9.
J Ethnopharmacol ; 247: 112273, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31586692

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Luohanguo (LHG), a traditional Chinese medicine, could clear heat, moisten the lung, soothe the throat, restore the voice, and lubricate intestine and open the bowels. LHG has been utilized for the treatment of sore throats and hyperglycemia in folk medicine as a homology of medicine and food. The hypoglycemic pharmacology of LHG has attracted considerable attention, and mogrosides have been considered to be active ingredients against diabetes mellitus. We have found that these mogrosides could be metabolized into their secondary glycosides containing 1-3 glucose residues in type 2 diabetes mellitus (T2DM) rats in previous studies. These metabolites may be the antidiabetic components of LHG in vivo. Thus far, no reports have been found on reducing blood glucose of mogrosides containing 1-3 glucose residues. AIMS OF THE STUDY: The aim of this study was to confirm that mogrosides containing 1-3 glucose residues were the active components of LHG for antidiabetic effects and to understand their potential mechanisms of action. MATERIALS AND METHODS: First, the special fraction of mogrosides containing 1-3 glucose residues was separated from a 50% ethanol extract of LHG, and the chemical components were identified by ultra-performance liquid chromatography (UPLC) and named low-polar Siraitia grosvenorii glycosides (L-SGgly). Second, the antidiabetic effects of L-SGgly were evaluated by HFD/STZ-induced (high-fat diet and streptozocin) obese T2DM rats by indexing fasting blood glucose (FBG), fasting insulin (FINS), and insulin resistance, and then compared with other fractions in the separation process. The changes in serum lipid levels were also detected. Finally, possible mechanisms of antidiabetic activity of L-SGgly were identified as increasing GLP-1 levels and activating liver AMPK in T2DM rats. RESULTS: The chemical analysis of L-SGgly showed that they contain 11-oxomogroside V, mogroside V, mogroside III, mogroside IIE, mogroside IIIA1, mogroside IIA1, and mogroside IA1, respectively. The total content of the mogrosides in L-SGgly was 54.4%, including 15.7% mogroside IIA1 and 12.6% mogroside IA1. L-SGgly showed excellent effects on obese T2DM rats compared with the other fractions of LHG extract, including significantly reducing the levels of FBG (p < 0.001) and modifying insulin resistance (p < 0.05). Meanwhile, they could significantly decrease the content of triglyceride (p < 0.01), total cholesterol (p < 0.01), low-density lipoprotein cholesterol (p < 0.01) and free fatty acid (p < 0.001) and increase the content of high-density lipoprotein cholesterol (p < 0.001) in serum of T2DM rats. Moreover, L-SGgly can significantly increase (p < 0.01) GLP-1 levels and decrease (p < 0.01) IL-6 levels in T2DM rat serum. AMPK-activating activity in T2DM rats was also upregulated by L-SGgly, but no statistical significance was shown. CONCLUSION: L-SGgly, fractions separated from LHG extract, were verified to have obvious anti-hyperglycemic and anti-hyperlipidemic effects on T2DM rats. Furthermore, L-SGgly regulated insulin secretion in T2DM rats by increasing GLP-1 levels. These findings provide an explanation for the antidiabetic role of LHG.


Assuntos
Cucurbitaceae/química , Diabetes Mellitus Tipo 2/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Glicosídeos/farmacologia , Hipoglicemiantes/farmacologia , Hipolipemiantes/farmacologia , Obesidade/tratamento farmacológico , Triterpenos/farmacologia , Administração Oral , Animais , Glicemia/análise , Glicemia/efeitos dos fármacos , Glicemia/metabolismo , Fracionamento Químico , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/etiologia , Dieta Hiperlipídica/efeitos adversos , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/uso terapêutico , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Glicosídeos/análise , Glicosídeos/isolamento & purificação , Glicosídeos/uso terapêutico , Humanos , Hipoglicemiantes/análise , Hipoglicemiantes/isolamento & purificação , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/análise , Hipolipemiantes/isolamento & purificação , Hipolipemiantes/uso terapêutico , Insulina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Masculino , Obesidade/sangue , Obesidade/etiologia , Ratos , Estreptozocina/toxicidade , Triterpenos/análise , Triterpenos/isolamento & purificação , Triterpenos/uso terapêutico
10.
J Ethnopharmacol ; 247: 112281, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31600559

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia annua L. is a heat-clearing Chinese medicine and well-known for its antimalarial constituent, artemisinin. It has gained increasing attention for its anti-inflammatory and immunoregulatory activities. Interestingly, the crude polysaccahrides of A. annua exhibited potent anticomplement activity. This study was to isolate and characterize its anticomplement homogeneous polysaccharides from A. annua, and reveal the relationship between structures and anticomplement activities of the isolated polysaccharides. MATERIALS AND METHODS: Water-soluble crude polysaccharides from the aerial parts of A. annua were extracted and fractionated by DEAE-cellulose and Sephacryl S-300 gel permeation chromatography. Homogeneity, molecular weight, monosaccharide composition, methylation and NMR analysis were performed to characterize the structures of homogeneous polysaccharides. Their anticomplement activities and targeting components in the complement activation cascade were evaluated by hemolytic assays. RESULTS: Three homogeneous polysaccharides (AAP01-1, AAP01-2 and AAP01-3) were obtained from A. annua. AAP01-1 was composed of seven monosaccharides, including mannose, rhamnose, glucuronic acid, galacturonic acid, glucose, galactose and arabinose. AAP01-2 and AAP01-3 had similar monosaccharides with AAP01-1, except the absence of glucuronic acid. They were all branched acidic heteropolysaccharides with different contents of galacturonic acid (8%, 28% and 15% for AAP01-1, AAP01-2 and AAP01-3, respectively). AAP01-2 showed potent anticomplement activity with CH50 value of 0.360 ±â€¯0.020 mg/mL through the classical pathway and AP50 value of 0.547 ±â€¯0.033 mg/mL through the alternative pathway. AAP01-3 exhibited slightly weaker activity (CH50: 1.120 ±â€¯0.052 mg/mL, AP50: 1.283 ±â€¯0.061 mg/mL), while AAP01-1 was inactive. Moreover, AAP01-2 acted on C1q, C3, C4, C5 and C9 components and AAP01-3 interacted with C3, C4 and C5 components in the activation cascade of complement system. CONCLUSION: These results indicated that the relatively high contents of galacturonic acid were important for anticomplement activities of the polysaccharides from A. annua. The anticomplement polysaccharides are another kind of bioactive constituents conferring heat-clearing effects of A. annua.


Assuntos
Artemisia annua/química , Ativação do Complemento/efeitos dos fármacos , Inativadores do Complemento/farmacologia , Medicamentos de Ervas Chinesas/farmacologia , Polissacarídeos/farmacologia , Animais , Bioensaio , Inativadores do Complemento/química , Inativadores do Complemento/isolamento & purificação , Proteínas do Sistema Complemento , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Cobaias , Hemólise/efeitos dos fármacos , Ácidos Hexurônicos/química , Ácidos Hexurônicos/isolamento & purificação , Ácidos Hexurônicos/farmacologia , Modelos Animais , Estrutura Molecular , Componentes Aéreos da Planta/química , Coelhos , Relação Estrutura-Atividade
11.
J Ethnopharmacol ; 247: 112283, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-31605736

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Bulbus Fritillaria cirrhosa D. Don (BFC) is a Chinese traditional herbal medicine that has long been used as an indispensable component in herbal prescriptions for bronchopulmonary diseases due to its well-established strong anti-inflammation and pulmonary harmonizing effects. Interestingly, there are few case reports in traditional Chinese medicine available where they found it to contribute in anti-tumor therapies. Imperialine is one of the most favored active substances extracted from BFC and has been widely recognized as an anti-inflammatory agent. AIM OF THE STUDY: The aim of the current work is to provide first-hand evidences both in vitro and in vivo showing that imperialine exerts anti-cancer effects against non-small cell lung cancer (NSCLC), and to explore the molecular mechanism of this anti-tumor activity. It is also necessary to examine its systemic toxicity, and to investigate how to develop strategies for feasible clinical translation of imperialine. MATERIALS AND METHODS: To investigate anti-NSCLC efficacy of imperialine using both in vitro and in vivo methods where A549 cell line were chosen as in vitro model NSCLC cells and A549 tumor-bearing mouse model was constructed for in vivo study. The detailed underlying anti-cancer mechanism has been systematically explored for the first time through a comprehensive set of molecular biology methods mainly including immunohistochemistry, western blot and enzyme-linked immunosorbent assays. The toxicity profile of imperialine treatments were evaluated using healthy nude mice by examining hemogram and histopathology. An imperialine-loaded liposomal drug delivery system was developed using thin film hydration method to evaluate target specific delivery. RESULTS: The results showed that imperialine could suppress both NSCLC tumor and associated inflammation through an inflammation-cancer feedback loop in which NF-κB activity was dramatically inhibited by imperialine. The NSCLC-targeting liposomal system was successfully developed for targeted drug delivery. The developed platform could favorably enhance imperialine cellular uptake and in vivo accumulation at tumor sites, thus improving overall anti-tumor effect. The toxicity assays revealed imperialine treatments did not significantly disturb blood cell counts in mice or exert any significant damage to the main organs. CONCLUSIONS: Imperialine exerts anti-cancer effects against NSCLC both in vitro and in vivo, and this previously unknown function is related to NF-κB centered inflammation-cancer feedback loop. Imperialine mediated anti-cancer activity is not through cytotoxicity and exhibit robust systemic safety. Furthermore, the liposome-based system we commenced would dramatically enhance therapeutic effects of imperialine while exhibiting extremely low side effects both on cellular and in NSCLC model. This work has identified imperialine as a promising novel anti-cancer compound and offered an efficient target-delivery solution that greatly facilitate practical use of imperialine.


Assuntos
Alcaloides/administração & dosagem , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cevanas/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Fritillaria/química , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Alcaloides/efeitos adversos , Alcaloides/química , Alcaloides/isolamento & purificação , Animais , Contagem de Células Sanguíneas , Carcinoma Pulmonar de Células não Pequenas/imunologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Cevanas/efeitos adversos , Cevanas/química , Cevanas/isolamento & purificação , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Retroalimentação Fisiológica/efeitos dos fármacos , Humanos , Lipossomos , Neoplasias Pulmonares/imunologia , Neoplasias Pulmonares/patologia , Masculino , Camundongos , NF-kappa B/antagonistas & inibidores , NF-kappa B/imunologia , Testes de Toxicidade , Ensaios Antitumorais Modelo de Xenoenxerto
12.
J Ethnopharmacol ; 248: 112328, 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-31654799

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Dalbergia odorifera, a traditional herbal medicine, has long been used in China for dissipating blood stasis, regulating the flow of qi, and relieving pain. AIM OF THIS REVIEW: This review aims to provide comprehensive and up-to-date information about the traditional uses, phytochemistry, pharmacology, and quality control of D. odorifera. Additionally, perspectives for possible future investigations on D. odorifera are also discussed. MATERIALS AND METHODS: Information on D. odorifera was obtained from a library database and electronic searches (e.g., Elsevier, Springer, ScienceDirect, Wiley, Web of Science, PubMed, Google Scholar, China Knowledge Resource Integrated). RESULTS: According to classical Chinese herbal texts and the Chinese Pharmacopoeia, D. odorifera promotes blood circulation, relieves pain, and eliminates blood stasis, and it can be used to treat cardio-cerebrovascular diseases in traditional Chinese medicine prescriptions. The chemical constituents of D. odorifera have been well studied, with approximately 175 metabolites having been identified, including flavonoids, phenols, arylbenzofurans, and quinones. The species also contains well-studied volatile oil. Its flavonoids and volatile oil are generally considered to be essential for its pharmacological activity. Modern pharmacology research has confirmed that isolated components and crude extracts of D. odorifera possess wide-ranging pharmacological effects, including anti-inflammatory, anti-angina, anti-oxidative, and other activities. Additionally, there are few quality control studies on D. odorifera. CONCLUSIONS: To date, significant progress has been made in D. odorifera phytochemistry and pharmacology. Thus, modern pharmacological research has provided some evidence for local or traditional uses. D. odorifera also showed therapeutic potential in cardiovascular and coronary heart diseases. However, the present findings are insufficient to explain its mechanisms of action. Additionally, the mechanism of heartwood formation, artificial induction technology for heartwood production, and quality control of D. odorifera require further detailed research.


Assuntos
Dalbergia , Medicamentos de Ervas Chinesas/uso terapêutico , Medicina Tradicional Chinesa , Fitoterapia , Animais , Dalbergia/química , Contaminação de Medicamentos/prevenção & controle , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/normas , Humanos , Medicina Tradicional Chinesa/normas , Fitoterapia/normas , Controle de Qualidade
13.
Molecules ; 24(23)2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31795252

RESUMO

Reactive oxygen/nitrogen species generated in the human body can cause oxidative damage associated with many degenerative diseases such as atherosclerosis, dementia, coronary heart diseases, aging, and cancer. There is a great interest in developing new antioxidants from Ganoderma fungus due to its low toxicity. As part of our ongoing search for antioxidative constituents from the fruiting bodies of Ganoderma lucidum, the chemical constituents were investigated and seven secondary metabolites, including one new lanostane triterpene (1), two known aromatic meroterpenoids (6-7), and four known triterpenes (2-5), were isolated by a series of chromatographic methods. The structures of the seven compounds were elucidated by spectroscopic techniques. The isolated compounds were tested in vitro for antioxidant potencies and neuroprotective activities against H2O2 and aged Aß-induced cell death in SH-SY5Y cells. As a result, compounds 1, 6, and 7 exhibited potent antioxidant and neuroprotective activities. Additionally, all isolated compounds were tested for radical scavenging activities. Compounds 6 and 7 showed the comparable free radical scavenging activities with the standard drug in both ABTS (2, 2'-azobis (3-ethylbenzothiazole-6-sulfonaic acid)) and ORAC (oxygen radical absorbance capacity) experiments. The results from this study suggested that G. lucidum and its metabolites (especially the meroterpenoids) may be potential functional food ingredients for the antioxidation and prevention of neurogenerative diseases.


Assuntos
Antioxidantes/farmacologia , Fármacos Neuroprotetores/farmacologia , Reishi/química , Terpenos/química , Terpenos/farmacologia , Triterpenos/química , Triterpenos/farmacologia , Antioxidantes/química , Antioxidantes/isolamento & purificação , Linhagem Celular Tumoral , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Estrutura Molecular , Fármacos Neuroprotetores/química , Fármacos Neuroprotetores/isolamento & purificação , Terpenos/isolamento & purificação , Triterpenos/isolamento & purificação
14.
Food Funct ; 10(12): 7913-7925, 2019 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-31793594

RESUMO

Fritillaria is a perennial herb with bulbs with multiple medicinal usages. Here, we optimized extraction and hydrolysis methods for different species and origins of Fritillaria to study their anti-inflammatory activities. Using ultrasound-assisted hot water extraction after hydrolysis by hydrochloric acid and trifluoroacetate (TFA), monosaccharide derived from 1-phenyl-3-methyl-5-pyrazolone (PMP) was separated by using HPLC. The optimal conditions for hot water extraction were found via single factor analysis and orthogonal experiments. The PMP derivatization HPLC method could accurately determine the Mannose (Man), Glucose (Glu), Galactose (Gal), Xylose (Xyl), and Fucose (Fuc) content values in Fritillaria. This pre-column derivatization method is simple and rapid, providing less variation, high sensitivity and good reproducibility for saccharide separation. To study Fritillaria's anti-inflammatory effects in a mouse swelling model, HE-staining was performed to observe morphological changes in liver and kidney samples. Fritillaria's active ingredients could significantly inhibit mouse ear swelling induced by xylene and inhibit toe swelling induced by egg white. They mainly inhibited the secretion of inflammatory cytokines inside the body and maintained the dynamic balance between pro-inflammatory and anti-inflammatory factors in the body. According to histopathological analysis, Fritillaria had good anti-inflammatory activity against LPS-induced inflammation, reducing the expression of inflammatory cytokines.


Assuntos
Anti-Inflamatórios/administração & dosagem , Medicamentos de Ervas Chinesas/administração & dosagem , Fritillaria/química , Inflamação/tratamento farmacológico , Polissacarídeos/administração & dosagem , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Citocinas/imunologia , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Feminino , Humanos , Inflamação/imunologia , Inflamação/patologia , Rim/efeitos dos fármacos , Rim/patologia , Fígado/efeitos dos fármacos , Fígado/patologia , Camundongos , Polissacarídeos/química , Polissacarídeos/isolamento & purificação
15.
Curr Top Med Chem ; 19(31): 2855-2867, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31724506

RESUMO

Gynostemma pentaphyllum (Thunb.) Makino (GpM) and its derivatives, especially gypenosides (Gyps), are widely used as safe and convenient natural herbal drugs for the treatment of many diseases for a long time, and Gyps have different oral bioavailability (OB) values and low ability to cross the blood-brain barrier (BBB). The effects of GpM and isolates on fibrosis, inflammation, oxidation, proliferation and migration are proved. GpM shows bidirectional regulation effect on proliferation, oxidation and apoptosis in tumor and non-tumor cells. GpM and its extractions can resist proliferation, activate oxidation and apoptosis in tumor cells and have opposite effects on non-tumor cells. We succinctly present some current views of medicinal value and potential therapeutic mechanisms of GpM and its derivatives.


Assuntos
Barreira Hematoencefálica/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Gynostemma/química , Neoplasias/tratamento farmacológico , Proliferação de Células/efeitos dos fármacos , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Humanos , Conformação Molecular , Neoplasias/metabolismo , Neoplasias/patologia
16.
Chin J Nat Med ; 17(10): 778-784, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31703758

RESUMO

Thibetanosides E-H (1-4), four new steroidal constituents including three rare sulfonates (2-4), were isolated from the roots and rhizomes of Helleborus thibetanus, together with nine known steroidal compounds (5-13). Their structures were elucidated by detailed spectroscopic analysis, including 1D and 2D NMR techniques and chemical evidence. In this study, compounds 2-13 were evaluated for their cytotoxic activities against HCT116, A549 and HepG2 tumor cell lines in vitro. Among them, compound 8 (thibetanoside C) showed cytotoxicities against A549 cells(IC50 39.6 ± 1.9 µmol·L-1) and HepG2 cells(IC50 41.5 ± 1.1 µmol·L-1), respectively. Compound 9 (23S, 24S)-24-[(O-ß-D-fucopyranosyl)oxy]-3ß, 23-dihydroxy-spirosta-5, 25(27)-diene-1ß-ylO-(4-O-acetyl- α-L-rhamnopyranosyl)-(1→2)-O-[ß-D-xylopyranosyl-(1→3)]-α-L-arabinopyranoside) showed cytotoxicity against HCT116 cells(IC50 33.6 ± 2.1 µmol·L-1).


Assuntos
Citotoxinas/química , Medicamentos de Ervas Chinesas/química , Helleborus/química , Esteroides/química , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Citotoxinas/isolamento & purificação , Citotoxinas/toxicidade , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/toxicidade , Humanos , Estrutura Molecular , Raízes de Plantas/química , Esteroides/isolamento & purificação , Esteroides/farmacologia
17.
Chin J Nat Med ; 17(10): 792-800, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31703760

RESUMO

Polysaccharide from traditional Chinese herb, Saposhnikovia divaricata (Turcz.) Schischk. (SD) was extracted, fractionated and characterized in this work. Four fractions were prepared. Their molecular weight, monosaccharide compositions, linkage modes and structural properties were characterized with SEC-MALS-RI, HPAEC-PAD, GC-MS and NMR. SDP1 was assigned as a 1, 4-α-glucan with small amount of O-6 linked branches. SDP2 contained a big amount of the 1, 4-α-glucan and a small amount of arabinogalactan, while SDP3 possessed relatively lower amount of the 1, 4-α-glucan and a big amount of the arabinogalactan. SDP4 was defined as a pectic arabinogalactan. Four fractions showed antioxidant activities in both molecular and cellular levels and their activity was ranked as SDP4 ≈ SDP3>SDP2>SDP1. The 1, 4-α-glucan in SDP1 had the weakest, while SDP3 and SDP4 showed similar and the highest antioxidant activity. The arabinogalactan was the major component of both SDP3 and SDP4, which significantly contributed to the antioxidant activity of SDP.


Assuntos
Antioxidantes/química , Antioxidantes/isolamento & purificação , Apiaceae/química , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/isolamento & purificação , Polissacarídeos/química , Polissacarídeos/isolamento & purificação , Animais , Antioxidantes/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Medicamentos de Ervas Chinesas/farmacologia , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Camundongos , Raízes de Plantas/química , Polissacarídeos/farmacologia , Células RAW 264.7
18.
J Sep Sci ; 42(23): 3579-3588, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31617304

RESUMO

The quantification of three alkaloids is important because quantitative study is a means of assessing the reliability of the experimental method, and three alkaloids of peimine, peiminine, and peimisine are main active ingredients in Chinese Pharmacopoeia 2015. An effective method based on the matrix solid-phase dispersion microextraction was developed for the extraction of alkaloid compounds in Fritillariae Thunbergii Bulbus. Target analytes were analyzed by capillary electrophoresis coupled with quadrupole time-of-flight mass spectrometry. The optimized experimental condition was that 50 mg Fritillariae Thunbergii Bulbus was blended homogeneously with 10 mg citric acid for 5 min. Two hundred microliters of water acidized by 1 mol/L hydrochloric acid (pH = 4.5) was selected to elute tested alkaloids. The results demonstrated that the investigated method had low limits of detection (1.32-1.59 ng/mL), good recoveries (86.63-98.12%), and reproducibility (relative standard deviations of peak areas < 0.87%). The proposed matrix solid-phase dispersion microextraction coupled with capillary electrophoresis combined with quadrupole time-of-flight mass spectrometry was successfully applied for the extraction of alkaloids in plants.


Assuntos
Alcaloides/análise , Alcaloides/isolamento & purificação , Medicamentos de Ervas Chinesas/análise , Medicamentos de Ervas Chinesas/isolamento & purificação , Eletroforese Capilar/métodos , Microextração em Fase Sólida/métodos , Espectrometria de Massas em Tandem/métodos , Cevanas/análise , Cevanas/isolamento & purificação , Limite de Detecção
19.
Molecules ; 24(19)2019 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-31597363

RESUMO

Two new triterpenoids, named kadsuricoccins A and B, together with three known ones, were isolated from the Li folk herb Heilaohu, the stems of Kadsura coccinea (Lem.) A. C. Smith, which was used for food and as a healthy supplement. Their structures were elucidated by comprehensive analyses of mass spectrometry (MS) and nuclear magnetic resonance (NMR) spectroscopic data. To search healthy components, an acetylcholinesterase (AChE) inhibitory activity test by Ellman's Method was conducted, kadsuricoccins A and B showed activity with the AChE inhibit index (AII) up to 68.96% ± 0.19% and 57.8% ± 0.11% at 94 nM (compared with positive control tacrine AII 79.80% ± 0.20%, 9.4 nM), respectively.


Assuntos
Inibidores da Colinesterase/isolamento & purificação , Inibidores da Colinesterase/farmacologia , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/farmacologia , Kadsura/química , Caules de Planta/química , Inibidores da Colinesterase/química , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/química , Ativação Enzimática/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Estrutura Molecular
20.
Carbohydr Polym ; 226: 115283, 2019 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-31582088

RESUMO

Deproteinization is a crucial step for the purification of polysaccharides from natural biomass. However, traditional deproteinization technologies often suffer from complicated operating processes and the usage of toxic chemical reagents. Herein, an advanced and universal deproteinization method based on dual-functional adsorbent consisted of preferential protein adsorption coating of tannic acid-FeIII (TA-FeIII) and magnetic Fe3O4 (Fe3O4@TA-FeIII, abbreviated as FTF NPs) was developed. The proposed FTF NPs showed remarkable efficiency to remove protein from Lycium barbarum L. polysaccharides (LBPs) with deproteinization ratio of 96%, higher than the typical Sevag method (85%). Detailed adsorption kinetics studies demonstrated deproteinization process reached equilibrium after 10 min, faster than other reported deproteinization adsorbents. Furthermore, FTF NPs are structurally and functionally nondestructive as regards LBPs without using organic reagents. Also, it exhibited widespread-use deproteinization performance to several common plant species. Therefore, the proposed nano-separation based on TA-FeIII complex is an advanced and universal tool to high-efficiently deproteinize plant polysaccharides.


Assuntos
Medicamentos de Ervas Chinesas/isolamento & purificação , Compostos Férricos/química , Polissacarídeos/isolamento & purificação , Taninos/química , Adsorção , Cinética , Lycium/metabolismo , Fenômenos Magnéticos
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