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1.
Am J Transl Res ; 16(1): 234-254, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38322552

RESUMO

Type 2 diabetes mellitus (T2DM), a common and frequently occurring disease in contemporary society, has become a global health threat. However, current mainstream methods of prevention and treatment, mainly including oral hypoglycemic drugs and insulin injections, do not fundamentally block the progression of T2DM. Therefore, it is imperative to find new ways to prevent and treat diabetes. Traditional Chinese medicine is characterized by multiple components, pathways, and targets with mild and long-lasting effects. Pharmacological studies have shown that nourishing yin traditional Chinese medicine (NYTCM) can play a positive role in the treatment of T2DM by regulating pathways such as the phosphatidylinositol 3-kinase/serine-threonine kinase, mitogen-activated protein kinase, nuclear factor-kappa B, and other pathways to stimulate insulin secretion, protect and repair pancreatic ß cells, alleviate insulin resistance, ameliorate disordered glucose and lipid metabolism, mitigate oxidative stress, inhibit inflammatory responses, and regulate the intestinal flora. The pharmacologic activity, mechanisms, safety, and toxicity of NYTCM in the treatment of T2DM are also reviewed in this manuscript.

2.
Fitoterapia ; 172: 105774, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38097021

RESUMO

Five novel lignans, namely styraxjaponica A-E (1-5), together with eight known compounds (6-13) were isolated from the leaves of Styrax japonicus Siebold & Zucc. Their chemical structures were characterized by extensive analysis of 1D and 2D NMR, UV, IR, HRESIMS spectroscopic analysis as well as by comparison to the literature. The absolute configurations of the new compounds were further determined by quantum chemical electronic circular dichroism (ECD) calculations powered by time-dependent density functional theory (TDDFT). Moreover, the anti-inflammatory effects of compounds 1-5 in lipopolysaccharide (LPS)-induced RAW 264.7 cells were also evaluated by measuring nitric oxide (NO) concentrations. All compounds displayed significant anti-inflammatory activity without affecting cell viability in vitro.


Assuntos
Lignanas , Lignanas/farmacologia , Lignanas/química , Styrax , Estrutura Molecular , Extratos Vegetais/química , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Óxido Nítrico
3.
Digital Chinese Medicine ; (4): 257-271, 2023.
Artigo em Inglês | WPRIM | ID: wpr-997647

RESUMO

@#[Objective[ To analyze the main syndrome types, medication rules, and core prescription characteristics of traditional Chinese medicine (TCM) in the treatment of metabolism-associated fatty liver disease (MAFLD), and to predict the anti-MAFLD mechanism of core formula, so as to provide references for the clinical application of TCM and the development of new drugs. [Methods] Literature research on TCM in treating MAFLD was retrieved from China National Knowledge Infrastructure (CNKI), China Science and Technology Journal Database (VIP), and Wanfang Database since the establishment of the database to July 2022. Excel 2019 and Chinese Medicine Inheritance Computing Platform (V3.0) were used for frequency analysis, association rule analysis, and cluster analysis of effective prescriptions. The key components, targets, and action pathways of anti-MAFLD core formulas were predicted by network pharmacology. Finally, the interactions between the obtained core components and their core targets were verified reversely by molecular docking technology. [Results] A total of 218 articles were screened and selected, including 352 prescriptions, involving 270 traditional Chinese herbs. The drugs were used a total of 3 901 times, and a total of 10 915 cases were collected, among which the prevalence rate was higher in males. The main types of TCM syndrome included intermingled phlegm and blood stasis syndrome, liver depression and spleen deficiency syndrome, and damp-heat in liver and gallbladder syndrome, among which Shanzha (Crataegi Fructus), Danshen (Salviae Miltiorrhizae Radix et Rhizoma), Fuling (Poria), Zexie (Alismatis Rhizoma), Chaihu (Bupleuri Radix), and Baizhu (Atractylodis Macrocephalae Rhizoma) were the most frequently used. The properties of Chinese medicine primarily encompassed thermal characteristics, with a predominant emphasis on cold and warm; the flavors of herbs were predominantly characterized by bitterness and sweetness, while the majority exhibited tropism towards the spleen and liver meridians. The drugs were primarily classified based on their efficacy in tonifying deficiencies, promoting diuresis and moistening, enhancing blood circulation and removing blood stasisheat-clearing, etc. The association rules were employed to derive a set of 20 core drug pairs, while cluster analysis was utilized to identify three distinct groups of core drug combinations. Network pharmacological showed that the main components of the core formula “Shanzha (Crataegi Fructus) - Danshen (Salviae Miltiorrhizae Radix et Rhizoma) - Zexie (Alismatis Rhizoma) - Chaihu (Bupleuri Radix) - Fuling (Poria)” in the treatment of MAFLD were quercetin, apigenin, puerarin, luteolin, ursolic acid, kaempferol, tanshinone IIA, emodin, paeonol, etc., which involved RAC-alpha serine/threonine-protein kinase 1 (AKT1), cellular tumor antigen p53 (TP53), interleukin (IL)-6, IL-1β, signal transducer and activator of transcription 3 (STAT3), epidermal growth factor receptor (EGFR), peroxisome proliferative activated receptor gamma (PPARG), and other key targets. The molecular docking results showed that the core components had good binding to lipid and atherosclerosis, and phosphatidylinositol 3 kinase (PI3K)/AKT signaling pathway-associated proteins. [Conclusion] The main principles of TCM for the treatment of MAFLD involve soothing the liver and strengthening the spleen, eliminating phlegm and dampness, clearing heat and dampness, as well as promoting blood circulation and removing blood stasis. The core formula may exert anti-MAFLD effects mediated through multiple components, targets, and signaling pathways. This study establishes a theoretical foundation for the clinical application of TCM in the treatment of MAFLD, and serves as a reference for further exploration of new drugs against MAFLD.

4.
PLoS One ; 16(3): e0248700, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33730076

RESUMO

As a traditional Chinese medicine (TCM) with a usage history of over 2,000 years in China, Spica Schizonepetae possesses definite clinical activity in the treatment of non-small cell lung cancer (NSCLC). However, its active ingredients and mechanism of action remain unclear at present. The further exploration of its active components and underlying mechanism will provide a basis for the development of candidate anti-tumor drugs. Our previous study explored the chemical constituents of Spica Schizonepetae extract (SSE). On this basis, molecular networking technology was applied in analyzing the QTOF-MS/MS data of rat plasma after intragastric administration of SSE using the GNPS database platform. A total of 26 components were found, including 9 proterotype components and 17 metabolites, which revealed the potential active ingredients of SSE. Later, the Lewis lung cancer mouse model was established, and the inhibition rate and histopathological sections were used as the indicators to investigate the anti-tumor effect of SSE, whereas the body weight, survival rate, thymus index and spleen index served as the indicators to explore the pharmacological effects of SSE on improving mouse immunity. The results showed that SSE had comparable anti-tumor efficacy to cisplatin, which enhanced the immunity, improved the quality of life, and extended the survival time of lung cancer mice. Furthermore, human A549 lung tumor cells were selected to explore the mechanism of SSE in treating NSCLC based on cell metabonomics. After data mining by the MPP software, 23 differential endogenous metabolites were identified between SSE and tumor groups. Moreover, results of pathway enrichment analysis using the MetaboAnalyst 4.0 software indicated that these metabolites were mainly enriched in four metabolic pathways (p < 0.1). By adopting the network pharmacology method, the metabolic pathways discovered by cell metabolomics were verified against the ChEMBL, STITCH, UniProt and TCGA databases, and differences in the underlying mechanism between cells and humans were found. It was proved that SSE affected the metabolism of purine, arachidonic acid and histidine to exert the anti-tumor efficacy. Furthermore, the multi-target, multi-pathway, and immunoenhancement mechanism of SSE in anti-tumor treatment was revealed, which provided a scientific basis for new drug development and the rational application of Spica Schizonepetae in clinic.


Assuntos
Carcinoma Pulmonar de Lewis/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Medicamentos de Ervas Chinesas/farmacologia , Lamiaceae/química , Neoplasias Pulmonares/tratamento farmacológico , Células A549 , Animais , Carcinoma Pulmonar de Lewis/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Modelos Animais de Doenças , Ensaios de Seleção de Medicamentos Antitumorais , Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/uso terapêutico , Humanos , Neoplasias Pulmonares/patologia , Masculino , Metabolômica , Camundongos , Ratos , Espectrometria de Massas em Tandem
5.
J Appl Physiol (1985) ; 115(8): 1146-55, 2013 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-23950164

RESUMO

l-Arginine (l-Arg) supplementation has been shown to enhance physical exercise capacity and delay onset of fatigue. This work investigated the potential beneficial mechanism(s) of l-Arg supplementation by examining its effect on the cellular oxidative and nitrosative stress pathways in the exercised rats. Forty-eight rats were randomly divided into six groups: sedentary control; sedentary control with l-Arg treatment; endurance training (daily swimming training for 8 wk) control; endurance training with l-Arg treatment; an exhaustive exercise (one time swimming to fatigue) control; and an exhaustive exercise with l-Arg treatment. l-Arg (500 mg/kg body wt) or saline was given to rats by intragastric administration 1 h before the endurance training and the exhaustive swimming test. Expression levels and activities of the l-Arg/nitric oxide (NO) pathway components and parameters of the oxidative stress and antioxidant defense capacity were investigated in l-Arg-treated and control rats. The result show that the l-Arg supplementation completely reversed the exercise-induced activation of NO synthase and superoxide dismutase, increased l-Arg transport capacity, and increased NO and anti-superoxide anion levels. These data demonstrate that l-Arg supplementation effectively reduces the exercise-induced imbalance between oxidative stress and antioxidant defense capacity, and this modulation is likely mediated through the l-Arg/NO pathways. The findings of this study improved our understanding of how l-Arg supplementation prevents elevations of reactive oxygen species and favorably enhances the antioxidant defense capacity during physical exercise.


Assuntos
Antioxidantes/farmacologia , Aorta Abdominal/efeitos dos fármacos , Arginina/farmacologia , Suplementos Nutricionais , Músculo Esquelético/efeitos dos fármacos , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Esforço Físico , Transdução de Sinais/efeitos dos fármacos , Sistemas de Transporte de Aminoácidos Básicos/metabolismo , Animais , Antioxidantes/metabolismo , Aorta Abdominal/metabolismo , Arginina/metabolismo , Ácido Láctico/sangue , Masculino , Fadiga Muscular/efeitos dos fármacos , Músculo Esquelético/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Condicionamento Físico Animal , Ratos , Ratos Sprague-Dawley , Comportamento Sedentário , Superóxido Dismutase/metabolismo , Natação , Fatores de Tempo , Tirosina/análogos & derivados , Tirosina/metabolismo
6.
PLoS One ; 8(2): e56407, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23437127

RESUMO

BACKGROUND: Nuclear factor-κB (NF-κB) is a central transcriptional factor and a pleiotropic regulator of many genes involved in acute lung injury. Andrographolide is found in the plant of Andrographis paniculata and widely used in Traditional Chinese Medicine, exhibiting potently anti-inflammatory property by inhibiting NF-κB activity. The purpose of our investigation was designed to reveal the effect of andrographolide on various aspects of LPS induced inflammation in vivo and in vitro. METHODS AND RESULTS: In vivo, BALB/C mice were subjected to LPS injection with or without andrographolide treatments to induce ALI model. In vitro, MLE-12 cells were stimulated with LPS in the presence and absence of andrographolide. In vivo, pulmonary inflammation, pulmonary edema, ultrastructure changes of type II alveolar epithelial cells, MPO activity, total cells, neutrophils, macrophages, TNF-α, IL-6 and IL-1ß in BALF, along with the expression of VCAM-1 and VEGF were dose-dependently attenuated by andrographolide. Meanwhile, in vitro, the expression of VCAM-1 and VEGF was also reduced by andrographolide. Moreover, our data showed that andrographolide significantly inhibited the ratios of phospho-IKKß/total IKKß, phospho-IκBα/total IκBα and phospho-NF-κB p65/total NF-κB p65, and NF-κB p65 DNA binding activities, both in vivo and in vitro. CONCLUSIONS: These results indicate that andrographolide dose-dependently suppressed the severity of LPS-induced ALI, more likely by virtue of andrographolide-mediated NF-κB inhibition at the level of IKKß activation. These results suggest andrographolide may be considered as an effective and safe drug for the potential treatment of ALI.


Assuntos
Lesão Pulmonar Aguda/tratamento farmacológico , Lesão Pulmonar Aguda/metabolismo , Diterpenos/uso terapêutico , NF-kappa B/metabolismo , Substâncias Protetoras/uso terapêutico , Lesão Pulmonar Aguda/genética , Lesão Pulmonar Aguda/patologia , Células Epiteliais Alveolares/patologia , Células Epiteliais Alveolares/ultraestrutura , Animais , Líquido da Lavagem Broncoalveolar , Contagem de Células , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , Citocinas/metabolismo , DNA/metabolismo , Diterpenos/farmacologia , Regulação para Baixo/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Lipopolissacarídeos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Peroxidase/metabolismo , Pneumonia/complicações , Pneumonia/tratamento farmacológico , Pneumonia/genética , Pneumonia/patologia , Substâncias Protetoras/farmacologia , Ligação Proteica/efeitos dos fármacos , Ligação Proteica/genética , Edema Pulmonar/complicações , Edema Pulmonar/tratamento farmacológico , Edema Pulmonar/genética , Edema Pulmonar/patologia , Fator de Transcrição RelA/metabolismo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/metabolismo , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo
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