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1.
Brief Bioinform ; 23(1)2022 01 17.
Artigo em Inglês | MEDLINE | ID: mdl-35057581

RESUMO

Pneumonia, especially corona virus disease 2019 (COVID-19), can lead to serious acute lung injury, acute respiratory distress syndrome, multiple organ failure and even death. Thus it is an urgent task for developing high-efficiency, low-toxicity and targeted drugs according to pathogenesis of coronavirus. In this paper, a novel disease-related compound identification model-based capsule network (CapsNet) is proposed. According to pneumonia-related keywords, the prescriptions and active components related to the pharmacological mechanism of disease are collected and extracted in order to construct training set. The features of each component are extracted as the input layer of capsule network. CapsNet is trained and utilized to identify the pneumonia-related compounds in Qingre Jiedu injection. The experiment results show that CapsNet can identify disease-related compounds more accurately than SVM, RF, gcForest and forgeNet.


Assuntos
Antivirais , Tratamento Farmacológico da COVID-19 , COVID-19 , Sistemas de Liberação de Medicamentos , Modelos Biológicos , Redes Neurais de Computação , SARS-CoV-2/metabolismo , Antivirais/química , Antivirais/farmacocinética , COVID-19/metabolismo , Humanos
2.
Biol Pharm Bull ; 46(5): 684-692, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37121694

RESUMO

Breast cancer, presented by multiple breast cancer subtypes that coexist within a diagnosed tumor in clinical, has ranked as the most common malignancy in women in recent years. Evidence suggested that limited effective drugs caused the unsatisfactory therapeutic efficacy of breast cancer. Flavokavain C exhibited anticancer activity on colon cancer cells HCT116. It is yet unknown if it can be used to treat breast cancer. This study aims to believe the mechanisms by which Flavokavain C suppresses cell proliferation and the pathways that impact on this effect in breast cancer. 3-(4,5-Dimethythiazol)-2,5-diphenyltetrazolium bromide assay was chosen to evaluate cell cytotoxicity. Colony formation and cell proliferation assays using 5-ethynyl-2'-deoxyuridine staining were performed. Cell cycle progression and apoptosis were examined via flow cytometry and Western blotting, respectively. Five methods (comet assay, immunofluorescence, Western blotting, agarose gel electrophoresis and molecular docking) were used to quantify DNA damage and its cellular response. Compared to cisplatin, Flavokavain C possessed a comparable or more substantial inhibitory effect on breast cancer cell viability while having lower cytotoxicity on human mammary cells. Breast cancer cells treated with Flavokavain C had their colony formation suppressed, DNA replication blocked, the G2/M phase cell cycle arrested, and apoptosis. Furthermore, the results indicated that Flavokavain C would directly interact with DNA and induce DNA cleavage, demonstrating that DNA is an attractive substrate for Flavokavain C. These results suggested that Flavokavain C had strong anticancer activity against multiple subtypes of breast cancer cells.


Assuntos
Neoplasias da Mama , Feminino , Humanos , Neoplasias da Mama/metabolismo , Sobrevivência Celular , Simulação de Acoplamento Molecular , Proliferação de Células , Apoptose , Dano ao DNA , Linhagem Celular Tumoral
3.
Chem Biodivers ; 20(4): e202200785, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36855022

RESUMO

Xanthii Fructus (XF) has been used for treatment of allergic rhinitis (AR), but its pharmacological mechanism of action remains unclear. We aimed to explore the potential mechanism of XF in treatment of AR by using a network pharmacology approach combined with in vivo verification experiments in this study. We identified 945 AR-related pathogenic genes, 11 active components in XF and 178 targets of those active components by corresponding databases. Finally, 54 targets of active components from XF in treatment of AR were identified by the Protein-protein interaction (PPI) network, Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis, among which Tumor Necrosis Factor (TNF), Mitogen-activated Protein Kinase 3 (MAPK3), Prostaglandin G/H Synthase 2 (PTGS2), Epidermal Growth Factor Receptor (EGFR) showed strongest interactions. The molecular docking analysis showed that moupinamide could bind to EGFR at LEU704 and LEU703, and PTGS2 at TRP387; 24-Ethylcholest-4-en-3-one was identified to bind to MAPK3 at THR347. The validation of quantitative real-time reverse transcription PCR (RT-PCR) showed that XF decreased the levels of MAPK3, PTGS2, and EGFR expression in the nasal mucosa from AR mice gavaged with an XF water decoction. Meanwhile, the levels of interleukin (IL)-4, IL-5 and IL-13were also decreased after the treatment of XF by Enzyme-linked immunosorbent assay (ELISA). Our results provide the pharmacological mechanism and possible intervention targets of XF in treatment of AR.


Assuntos
Medicamentos de Ervas Chinesas , Farmacologia em Rede , Rinite Alérgica , Animais , Camundongos , Ciclo-Oxigenase 2 , Medicamentos de Ervas Chinesas/farmacologia , Receptores ErbB , Simulação de Acoplamento Molecular , Farmacologia em Rede/métodos , Rinite Alérgica/tratamento farmacológico
4.
Medicina (Kaunas) ; 59(4)2023 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-37109624

RESUMO

Background and Objectives: Aucklandiae Radix is a well-known medicinal herb that is often used to treat gastric ulcer, but its molecular mechanism of anti-ulcer action is poorly understood. This research aimed to reveal the potential active components, core targets, and mechanisms of Aucklandiae Radix in treating gastric ulcer by combining network pharmacology and animal experimentation. Materials and Methods: First, a network pharmacology strategy was used to predict the main components, candidate targets, and potential signaling pathways. Molecular docking was then used to confirm the binding affinity between the main components and primary targets. Finally, rats were treated with indomethacin 30 mg/kg to establish a gastric ulcer model. Aucklandiae Radix extract (0.15, 0.3, and 0.6 g/kg) was pre-treated in rats by oral gavage for 14 days, and the protective effect and candidate targets of network pharmacology were validated through morphological observation, pathological staining, and biochemical index detection. Results: A total of eight potential active components and 331 predicted targets were screened from Aucklandiae Radix, 37 of which were common targets with gastric ulcer. According to the component-target network and protein-protein interaction (PPI) network, stigmasterol, mairin, sitosterol, and dehydrocostus lactone were identified as the key components, and RAC-alpha serine/threonine-protein kinase (AKT1), prostaglandin-endoperoxide synthase 2 (PTGS2), interleukin 1 beta (IL1B), caspase-3 (CASP3), and CASP8 were selected as the core targets. Gene ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment results revealed the pharmacological mechanism of Aucklandiae Radix against gastric ulcer related to many biological processes and pathways, including antibacterial, anti-inflammatory, prostaglandin receptor response, and apoptosis. Molecular docking verification showed that the key components and core targets had good binding affinities. In the in vivo experiments, Aucklandiae Radix notably relieved the gastric ulcer by reducing the levels of tumor necrosis factor (TNF)-α, interleukin (IL)-1ß, and myeloperoxidase (MPO) while improving the gastric histopathological features. Conclusion: The overall findings suggest that Aucklandiae Radix treats gastric ulcer with a multi-component, multi-target, and multi-mechanism model.


Assuntos
Úlcera Gástrica , Animais , Ratos , Úlcera Gástrica/tratamento farmacológico , Simulação de Acoplamento Molecular , Farmacologia em Rede , Fator de Necrose Tumoral alfa , Ciclo-Oxigenase 2
5.
Zhongguo Zhong Yao Za Zhi ; 48(6): 1597-1605, 2023 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-37005848

RESUMO

The purpose of this study is to investigate whether chrysin reduces cerebral ischemia-reperfusion injury(CIRI) by inhi-biting ferroptosis in rats. Male SD rats were randomly divided into a sham group, a model group, high-, medium-, and low-dose chrysin groups(200, 100, and 50 mg·kg~(-1)), and a positive drug group(Ginaton, 21.6 mg·kg~(-1)). The CIRI model was induced in rats by transient middle cerebral artery occlusion(tMCAO). The indexes were evaluated and the samples were taken 24 h after the operation. The neurological deficit score was used to detect neurological function. The 2,3,5-triphenyl tetrazolium chloride(TTC) staining was used to detect the cerebral infarction area. Hematoxylin-eosin(HE) staining and Nissl staining were used to observe the morphological structure of brain tissues. Prussian blue staining was used to observe the iron accumulation in the brain. Total iron, lipid pero-xide, and malondialdehyde in serum and brain tissues were detected by biochemical reagents. Real-time quantitative polymerase chain reaction(RT-qPCR), immunohistochemistry, and Western blot were used to detect mRNA and protein expression of solute carrier fa-mily 7 member 11(SLC7A11), transferrin receptor 1(TFR1), glutathione peroxidase 4(GPX4), acyl-CoA synthetase long chain family member 4(ACSL4), and prostaglandin-endoperoxide synthase 2(PTGS2) in brain tissues. Compared with the model group, the groups with drug intervention showed restored neurological function, decreased cerebral infarction rate, and alleviated pathological changes. The low-dose chrysin group was selected as the optimal dosing group. Compared with the model group, the chrysin groups showed reduced content of total iron, lipid peroxide, and malondialdehyde in brain tissues and serum, increased mRNA and protein expression levels of SLC7A11 and GPX4, and decreased mRNA and protein expression levels of TFR1, PTGS2, and ACSL4. Chrysin may regulate iron metabolism via regulating the related targets of ferroptosis and inhibit neuronal ferroptosis induced by CIRI.


Assuntos
Isquemia Encefálica , Ferroptose , Traumatismo por Reperfusão , Ratos , Masculino , Animais , Ratos Sprague-Dawley , Transdução de Sinais , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/genética , Isquemia Encefálica/metabolismo , Ciclo-Oxigenase 2/metabolismo , RNA Mensageiro , Infarto Cerebral , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , Malondialdeído , Infarto da Artéria Cerebral Média
6.
Zhongguo Zhong Yao Za Zhi ; 48(1): 279-284, 2023 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-36725281

RESUMO

At present, new concepts, new technologies, and new methods are emerging in the field of medical research, breaking through the inherent thinking patterns and research models, and promoting the transformation of the research paradigm of traditional Chinese medicine(TCM). This paper gave a case study of clinical research in Danhong Injection in the treatment of chronic stable angina, and based on the background of the study, index evaluation model, experimental design method, blind implementation of placebo, data management system, and exploration of clinical efficacy mechanism of traditional Chinese medicine compounds under the framework of modular pharmacology, the scientific idea of "proving efficacy, conforming standard, and exploring mechanism" was used as the guideline to discuss the research model of reevaluation of the effectiveness of post-marketing TCM varieties. This paper drew a target network map of Danhong Injection in the treatment of chronic stable angina for the first time, which was composed of targeted functional modules. By combining evidence-based clinical research with modular pharmacology framework, changes in the pharmacolo-gical mechanism were finally associated with changes in clinical efficacy, and the advantages of phenotypic correlation of efficacy were explored. This study is expected to provide references for the post-marketing effectiveness evaluation and new ideas for the phenotypic pharmacological mechanism study of multi-target TCM compounds and precise treatment, thereby promoting the innovative development of TCM.


Assuntos
Angina Estável , Medicamentos de Ervas Chinesas , Humanos , Medicina Tradicional Chinesa , Angina Estável/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/uso terapêutico , Resultado do Tratamento
7.
Pharmacol Res ; 184: 106419, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-36041653

RESUMO

In recent years, the strategy for tumor therapy has changed from focusing on the direct killing effect of different types of therapeutic agents on cancer cells to the new mainstream of multi-mode and -pathway combined interventions in the microenvironment of the developing tumor. Flavonoids, with unique tricyclic structures, have diverse and extensive immunomodulatory and anti-cancer activities in the tumor microenvironment (TME). Tumor-associated macrophages (TAMs) are the most abundant immunosuppressive cells in the TME. The regulation of macrophages to fight cancer is a promising immunotherapeutic strategy. This study covers the most comprehensive cognition of flavonoids in regulating TAMs so far. Far more than a simple list of studies, we try to dig out evidence of crosstalk at the molecular level between flavonoids and TAMs from literature, in order to discuss the most relevant chemical structure and its possible relationship with the multimodal pharmacological activity, as well as systematically build a structure-activity relationship between flavonoids and TAMs. Additionally, we point out the advantages of the macro-control of flavonoids in the TME and discuss the potential clinical implications as well as areas for future research of flavonoids in regulating TAMs. These results will provide hopeful directions for the research of antitumor drugs, while providing new ideas for the pharmaceutical industry to develop more effective forms of flavonoids.


Assuntos
Flavonoides , Macrófagos Associados a Tumor , Flavonoides/química , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Relação Estrutura-Atividade
8.
Molecules ; 27(19)2022 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-36235012

RESUMO

Polydatin is a natural potent stilbenoid polyphenol and a resveratrol derivative with improved bioavailability. Polydatin possesses potential biological activities predominantly through the modulation of pivotal signaling pathways involved in inflammation, oxidative stress, and apoptosis. Various imperative biological activities have been suggested for polydatin towards promising therapeutic effects, including anticancer, cardioprotective, anti-diabetic, gastroprotective, hepatoprotective, neuroprotective, anti-microbial, as well as health-promoting roles on the renal system, the respiratory system, rheumatoid diseases, the skeletal system, and women's health. In the present study, the therapeutic targets, biological activities, pharmacological mechanisms, and health benefits of polydatin are reviewed to provide new insights to researchers. The need to develop further clinical trials and novel delivery systems of polydatin is also considered to reveal new insights to researchers.


Assuntos
Polifenóis , Estilbenos , Feminino , Glucosídeos/farmacologia , Glucosídeos/uso terapêutico , Humanos , Resveratrol , Estilbenos/farmacologia , Estilbenos/uso terapêutico
9.
Zhongguo Zhong Yao Za Zhi ; 47(7): 1790-1801, 2022 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-35534249

RESUMO

This study aims to establish a method for analyzing the chemical constituents in Cistanches Herba by high performance liquid chromatography(HPLC) and quadrupole-time-of-flight tandem mass spectrometry(HPLC-Q-TOF-MS/MS), and to reveal the pharmacological mechanism based on network pharmacology for mining the quality markers(Q-markers) of Cistanches Herba. The chemical constituents of Cistanche deserticola and C. tubulosa were analyzed via HPLC-Q-TOF-MS/MS. The potential targets and pathways of Cistanches Herba were predicted via SwissTargetPrediction and DAVID. The compound-target-pathway-pharmacological action-efficacy network was constructed via Cytoscape. A total of 47 chemical constituents were identified, involving 95 targets and 56 signaling pathways. We preliminarily elucidated the pharmacological mechanisms of echinacoside, acteoside, isoacteoside, cistanoside F, 2'-acetylacteoside, cistanoside A, campneoside Ⅱ, salidroside, tubuloside B, 6-deoxycatalpol, 8-epi-loganic acid, ajugol, bartsioside, geniposidic acid, and pinoresinol 4-O-ß-D-glucopyranoside, and predicted them to be the Q-markers of Cistanches Herba. This study identified the chemical constituents of Cistanches Herba, explained the pharmacological mechanism of the traditional efficacy of Cistanches Herba based on network pharmacology, and introduced the core concept of Q-markers to improve the quality evaluation of Cistanches Herba.


Assuntos
Cistanche , Medicamentos de Ervas Chinesas , Cromatografia Líquida de Alta Pressão/métodos , Medicamentos de Ervas Chinesas/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Farmacologia em Rede , Espectrometria de Massas em Tandem/métodos
10.
Phytother Res ; 35(9): 4943-4956, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33860974

RESUMO

Bacterial vaginosis (BV) is a common disease among women of reproductive age, with a serious impact on their daily life and health. At present, the most common treatment for BV is to take antibiotics, which results in good short-term treatment effects, but poor long-term effects. Traditional Chinese medicine (TCM) has been used to treat BV for over a millennium, with little risk of triggering drug resistance and adverse effects. Based on syndrome differentiation, there are three oral TCM treatment strategies for BV, including invigorating spleen, clearing dampness and heat, and nourishing kidney. The oral TCM prescriptions, such as Yi Huang decoction, Longdan Xiegan decoction, Zhibai Dihaung decoction, and so on are commonly used. Topical TCM treatment is also popular in China. According to the research results of pharmacological effects of active TCM ingredients, the most potential mechanisms of TCM for BV treatment are immune-enhancement effects, antibacterial activity, and estrogen-liked effects. Nonetheless, the multi-constituent of herbs may result in possible disadvantages to BV treatment, and the pharmacological mechanisms of TCM need further study. Here, we provide an overview of TCM compounds and their preparations used for BV, based on the pathogenesis and the potential therapeutic mechanisms, therefore providing a reference for further studies.


Assuntos
Medicamentos de Ervas Chinesas , Vaginose Bacteriana , China , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Humanos , Medicina Tradicional Chinesa , Vaginose Bacteriana/tratamento farmacológico
11.
Zhongguo Zhong Yao Za Zhi ; 45(8): 1909-1917, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32489077

RESUMO

To construct the active component-action target network diagram and protein-protein interaction(PPI) network diagram of Aurantii Fructus Immaturus volatile oil, so as to explore the mechanism of Aurantii Fructus Immaturus volatile oil in the treatment of slow transit constipation(STC) by analyzing the functions and pathways involved in the target. The chemical constituents of Aurantii Fructus Immaturus volatile oil were determined by gas chromatography-mass spectrometry(GC-MS). The targets of Aurantii Fructus Immaturus volatile oil were studied by PubChem, TCMSP, STITCH and Swiss Target Prediction. OMIM, Genecards-Search Resuits and TTD were used to screen out the targets of Slow Transit Constipation. The active component-action targets and PPI network diagram were constructed by Cytoscape 3.7.1. The target organ distribution was analyzed by BioGPS database. GO and KEGG pathways involved in the targets were analyzed by R language. The molecular docking between the components and the targets was verified by Discovery Studio 2.5 software. Finally, 15 volatile oil compounds from Aurantii Fructus Immaturus were detected, and 115 targets of volatile oil in the treatment of STC were predicted. GO enrichment analysis showed that the activity of Aurantii Fructus Immaturus volatile oil mainly involved blood circulation, circulation system process, response to steroid hormone, signal release and other biological processes. There were 23 KEGG enrichment pathways, among which Neuroactive ligand-receptor interaction, cAMP signaling pathway, Endocrine resistance, Calcium signaling pathway and Serotonergic synapse pathways played a significant role in STC. The results of molecular docking showed that relevant target proteins for the treatment of STC were ACHE, PTGS2, SLC6 A2 and CNR2.The multi-component, multi-target and multi-pathwaycharacteristics of Aurantii Fructus Immaturus volatile oil were revealed by network pharmacology, which provided a new therapeutic idea and method for the further study of the mechanism of Aurantii Fructus Immaturus volatile oil in the treatment of STC.


Assuntos
Citrus , Medicamentos de Ervas Chinesas , Óleos Voláteis , Constipação Intestinal , Humanos , Simulação de Acoplamento Molecular
12.
J Cell Mol Med ; 23(12): 7946-7960, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31622015

RESUMO

Coptisine is a natural small-molecular compound extracted from Coptis chinensis (CC) with a history of using for thousands of years. This work aimed at summarizing coptisine's activity and providing advice for its clinical use. We analysed the online papers in the database of SciFinder, Web of Science, PubMed, Google scholar and CNKI by setting keywords as 'coptisine' in combination of 'each pivotal pathway target'. Based on the existing literatures, we find (a) coptisine exerted potential to be an anti-cancer, anti-inflammatory, CAD ameliorating or anti-bacterial drug through regulating the signalling transduction of pathways such as NF-κB, MAPK, PI3K/Akt, NLRP3 inflammasome, RANKL/RANK and Beclin 1/Sirt1. However, we also (b) observe that the plasma concentration of coptisine demonstrates obvious non-liner relationship with dosage, and even the highest dosage used in animal study actually cannot reach the minimum concentration level used in cell experiments owing to the poor absorption and low availability of coptisine. We conclude (a) further investigations can focus on coptisine's effect on caspase-1-involved inflammasome assembling and pyroptosis activation, as well as autophagy. (b) Under circumstance of promoting coptisine availability by pursuing nano- or microrods strategies or applying salt-forming process to coptisine, can it be introduced to clinical trial.


Assuntos
Berberina/análogos & derivados , Coptis/química , Transdução de Sinais/efeitos dos fármacos , Antibacterianos/farmacologia , Anti-Inflamatórios/farmacologia , Antinematódeos/farmacologia , Autofagia/efeitos dos fármacos , Berberina/química , Berberina/metabolismo , Berberina/farmacocinética , Berberina/farmacologia , Disponibilidade Biológica , Doenças Cardiovasculares/tratamento farmacológico , Coptis/metabolismo , Humanos , Inflamassomos/efeitos dos fármacos , Piroptose/efeitos dos fármacos
13.
Molecules ; 24(18)2019 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-31489932

RESUMO

Erding granule (EDG) is a traditional Chinese medicine that has recently been identified as having anti-hypouricemic effects. However, the active components and underlying mechanism for this new indication have not been elucidated. Therefore, we compared the effects of different EDG extracts (water, 50% ethanol and 95% ethanol) on serum uric acid concentrations in the hyperuricemia model mouse. We also analyzed the constituents of different extracts by ultra-high performance liquid chromatography combined with electrospray ionization quadrupole time-of-flight mass spectrometry (UHPLC-Q-TOF-MS/MS) to observe the variation between the active and inactive products. Extract activity and target site were evaluated by assessing uric acid- and inflammation-suppressing effects along with evaluating ability to regulate the uric acid transporter. The results showed that the 50% ethanol extract (EDG-50) had an obvious serum uric acid concentration lowering effect compared with water (EDG-S) and the 95% ethanol extract (EDG-95). UHPLC-Q-TOF-MS/MS analysis showed that EDG-50 was compositionally different to EDG-S and EDG-95. EDG-50 showed dose-dependent effects on reducing uric acid, suppressing inflammation and regulating uric acid transporters. Moreover, western blot analysis showed that EDG-50 down-regulated GLUT9 and URAT1 expression, and up-regulated OAT1 expression. Therefore, our findings enable the preliminarily conclusion that EDG-50 lowers serum uric acid concentrations, mainly by down-regulating the expression of GLUT9 and URAT1 proteins and up-regulating the expression of OAT1 proteins. This provides a research basis for clinical use of EDG as an anti-hyperuricemic agent.


Assuntos
Anti-Inflamatórios/administração & dosagem , Medicamentos de Ervas Chinesas/química , Etanol/administração & dosagem , Hiperuricemia/tratamento farmacológico , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Cromatografia Líquida de Alta Pressão , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Etanol/química , Etanol/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Proteínas Facilitadoras de Transporte de Glucose/metabolismo , Hiperuricemia/metabolismo , Masculino , Camundongos , Transportadores de Ânions Orgânicos/metabolismo , Ratos , Ratos Sprague-Dawley , Espectrometria de Massas por Ionização por Electrospray , Ácido Úrico/sangue
14.
Zhongguo Zhong Yao Za Zhi ; 44(19): 4225-4233, 2019 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-31872703

RESUMO

Nelumbinis Plumula has the traditional sedative effect,but its mechanism is unclear. In this study,the relationship between traditional sedative effect and hypnotic effect of Nelumbinis Plumula was taken as the starting point to study the hypnotic mechanism of the major medicinal components in Nelumbinis Plumula by the network pharmacology method. Targets of active Nelumbinis Plumula alkaloids were screened by Swiss Target Prediction server,TCMSP and BATMAN-TCM. Targets of hypnotic drugs approved by FDA were screened from Drug Bank,OMIM,TTD databases. The common targets were screened by GO and KEGG pathways. Cytoscape 3. 7. 1 software was used to construct the network of " active component-target-pathway-disease". The results of network analysis showed that 21 active compounds were associated with 44 targets and 28 pathways. Among them,21 compounds,35 targets and 15 pathways were predicted to be related to sedative hypnosis. Nelumbinis Plumula showed the hypnotic effect by acting on neuroactive ligand-receptor interaction pathway,regulation of actin cytoskeleton pathway,calcium signaling pathway,cholinergic synapse pathway.This study preliminarily revealed the potential active compounds and possible mechanisms of traditional sedative effect of Nelumbinis Plumula,which provided a theoretical basis for further experimental studies on medicinal materials and its mechanisms.


Assuntos
Alcaloides , Medicamentos de Ervas Chinesas , Hipnóticos e Sedativos
15.
Pharmacology ; 102(3-4): 142-153, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30016781

RESUMO

AIM: Previous studies have suggested that quercetin is effective for treating diverse chronic disorders including organ fibrosis and airway and cardiovascular disorders. To access the pharmacological background for its broad efficacy, we examined the ability of quercetin to modulate the inflammatory and fibrotic responses associated with organ injury that commonly underlie the pathogenesis of those disorders. METHODS: A cutaneous wound model on rabbit ear was used for in vivo study. Quercetin was topically applied to the wounds, and the number of macrophages and myofibroblasts and the size of the hypertrophic scar formed were estimated. An in vitro study examined the ability of quercetin to inhibit cell-signaling pathways that activate RAW264.7 macrophages and primary dermal fibroblasts and the tyrosine kinase activity of discoidin domain receptor 2. RESULTS: Quercetin reduced the population of macrophages and myofibroblasts and the scar formation in cutaneous wound healing. Quercetin suppressed the signaling pathways activating RAW264.7 macrophages and dermal fibroblasts, which is associated with its inhibition of multiple tyrosine kinases to regulate the pathways. This pharmacological activity of quercetin to simultaneously inhibit the inflammatory and fibrotic responses upon tissue damage by targeting multi-kinases could be the action mechanism to support its broad efficacy for various chronic disorders.


Assuntos
Receptor com Domínio Discoidina 2/antagonistas & inibidores , Inibidores Enzimáticos/farmacologia , Fibrose/tratamento farmacológico , Inflamação/tratamento farmacológico , Miofibroblastos/efeitos dos fármacos , Quercetina/farmacologia , Ferimentos e Lesões/tratamento farmacológico , Animais , Anti-Inflamatórios/metabolismo , Ciclo-Oxigenase 2/metabolismo , Receptor com Domínio Discoidina 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Feminino , Fibrose/enzimologia , Fibrose/patologia , Inflamação/metabolismo , Macrófagos/efeitos dos fármacos , Macrófagos/enzimologia , Macrófagos/patologia , Camundongos , Camundongos Endogâmicos BALB C , Miofibroblastos/enzimologia , Miofibroblastos/patologia , Óxido Nítrico Sintase Tipo II/metabolismo , Cultura Primária de Células , Células RAW 264.7 , Coelhos , Ferimentos e Lesões/enzimologia , Ferimentos e Lesões/patologia
16.
Int J Mol Sci ; 20(1)2018 Dec 24.
Artigo em Inglês | MEDLINE | ID: mdl-30586944

RESUMO

Sinomenine (SIN) is widely used in China to treat a variety of rheumatic diseases (RA), and has various pharmacological effects such as anti-inflammatory, analgesic, and anti-tumor effects. However, due to the histamine release characteristics of SIN, its adverse reactions such as allergic reactions, gastrointestinal reactions, and circulatory systemic reactions have been drawing increasing attention. We present here a systematic review of the chemical structure, pharmacological effects, clinical application, and adverse reactions of SIN, a detailed discussion on the relationship between histamine/histamine receptor and mechanism of action of SIN. In addition, we simulated the binding of SIN to four histamine receptors by using a virtual molecular docking method and found that the bonding intensity between SIN and receptors varied in the order shown as follows: H1R > H2R ~ H3R > H4R. The docking results suggested that SIN might exhibit dual regulatory effects in many processes such as cyclooxygenase-2 (COX-2) expression, NF-κB pathway activation, and degranulation of mast cells to release histamine, thereby exhibiting pro-inflammatory (adverse reactions)/anti-inflammatory effects. This study provides a theoretical basis for the clinical treatment of inflammations seen such as in RA using SIN, and also suggests that SIN has great potential in the field of cancer treatment and will have very important social and economic significance.


Assuntos
Imunossupressores/metabolismo , Morfinanos/metabolismo , Receptores Histamínicos/metabolismo , Ciclo-Oxigenase 2/metabolismo , Doenças Hematológicas/etiologia , Liberação de Histamina , Humanos , Imunossupressores/efeitos adversos , Imunossupressores/uso terapêutico , Simulação de Acoplamento Molecular , Morfinanos/química , Morfinanos/uso terapêutico , Ligação Proteica , Receptores Histamínicos/química , Doenças Reumáticas/tratamento farmacológico
17.
Molecules ; 22(8)2017 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-28820497

RESUMO

The majority of currently used anesthetic agents are derived from or associated with natural products, especially plants, as evidenced by cocaine that was isolated from coca (Erythroxylum coca, Erythroxylaceae) and became a prototype of modern local anesthetics and by thymol and eugenol contained in thyme (Thymus vulgaris, Lamiaceae) and clove (Syzygium aromaticum, Myrtaceae), respectively, both of which are structurally and mechanistically similar to intravenous phenolic anesthetics. This paper reviews different classes of phytochemicals with the anesthetic activity and their characteristic molecular structures that could be lead compounds for anesthetics and anesthesia-related drugs. Phytochemicals in research papers published between 1996 and 2016 were retrieved from the point of view of well-known modes of anesthetic action, that is, the mechanistic interactions with Na⁺ channels, γ-aminobutyric acid type A receptors, N-methyl-d-aspartate receptors and lipid membranes. The searched phytochemicals include terpenoids, alkaloids and flavonoids because they have been frequently reported to possess local anesthetic, general anesthetic, antinociceptive, analgesic or sedative property. Clinical applicability of phytochemicals to local and general anesthesia is discussed by referring to animal in vivo experiments and human pre-clinical trials. This review will give structural suggestions for novel anesthetic agents of plant origin.


Assuntos
Anestésicos Locais/uso terapêutico , Anestésicos/uso terapêutico , Compostos Fitoquímicos/uso terapêutico , Anestésicos/química , Anestésicos Locais/classificação , Cocaína/uso terapêutico , Eugenol/química , Eugenol/uso terapêutico , Humanos , Compostos Fitoquímicos/classificação , Syzygium/química , Timol/química , Timol/uso terapêutico , Thymus (Planta)/química
18.
Zhongguo Zhong Yao Za Zhi ; 42(23): 4556-4564, 2017 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-29376252

RESUMO

Guizhi Decoction was one of the most commonly used traditional Chinese Medicine which possesses the effects of "jie-ji-fa-biao, regulating Ying and Wei". It was mainly used to treat mind-cold due to exogenous evils such as fever, headache, sweating, hate the wind, et al. Modern studies indicated that the chemical constituents of Guizhi decoction mainly include phenylpropanoid, monoterpenes, organic acids, flavonoids, triterpenoid saponins and so on. Pharmacological experimental studies had shown that Guizhi decoction could play a big role in dual-directional regulation on sweat gland, body temperature, immune function, gastrointestinal peristalsis, and blood pressure, and could also play the role of anti-inflammatory, antibacterial, antiviral, anti-allergic, analgesic, hypoglycemic, and cardiovascular protection. Many diseases such as internal, external, gynecological and pediatric diseases were treated in the clinical by using Guizhi decoction and its analogous formulae involving circulatory, immune, urinary, reproductive, endocrine, digestive, nervous and other systems. This article reviews the latest research progress of Guizhi decoction from three aspects: chemical constituents, pharmacological mechanism and clinical application. It will provide reference for further research and development of Guizhi decoction.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Medicina Tradicional Chinesa , Pesquisa
19.
Zhongguo Zhong Yao Za Zhi ; 42(19): 3645-3649, 2017 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-29235273

RESUMO

Traditional Chinese medicine(TCM) is a complex system with multiple chemical compositions. The most significant character of TCM is that the chemical compositions interact with each other by multi-target synergism to treat diseases. Previous reports mainly focused on the investigation of single signaling pathway detection or the phenotypic analysis of proteomics difference; however, no studies have been conducted on the identification of direct targets of TCM. Therefore, it is difficult to analyze the molecular mechanism of traditional Chinese medicine from the target source, and it is difficult to explain its traditional efficacy scientifically, thus seriously affecting its clinical application and internationalization. In this article, we discussed the methodology for the identification of direct TCM targets(groups), and presented the strategy for preparation of TCM chemical composition solid coupling beads, as well as of enrichment and identification strategy of target proteins based on photosensitive coupling technique. We also discussed the advantages and limitations of this strategy, and put forward some new ideas for the future developments. We hope this article can provide some guidance and reference significance for the researchers on TCM pharmacology study, especially on target identification.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicina Tradicional Chinesa , Sistemas de Liberação de Medicamentos
20.
Biomed Pharmacother ; 171: 116146, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38198952

RESUMO

The effectiveness and safety of traditional Chinese medicine's active ingredients in anti-tumor effects have attracted widespread attention worldwide. Solasonine is the main anti-tumor component of the traditional Chinese medicine Solanum nigrum L, which can inhibit tumor cell proliferation, induce apoptosis, induce ferroptosis in tumor cells, and inhibit of tumor cell metastasis, thereby inhibiting tumor progression. Therefore, we summarized anti-tumor mechanisms and targets of solasonine to provide new ideas and theoretical basis for its further development and application.


Assuntos
Neoplasias , Alcaloides de Solanáceas , Humanos , Alcaloides de Solanáceas/farmacologia , Apoptose , Medicina Tradicional Chinesa
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