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1.
Artigo em Inglês | MEDLINE | ID: mdl-34824593

RESUMO

Trichosanthes kirilowii Maxim. and Bulbus allii Macrostemi are the components of Gualou Xiebai decoction (GLXB), a commonly used herbal combination for the treatment of coronary heart disease (CHD) in traditional Chinese medicine. Although GLXB is associated with a good clinical effect, its active compounds and mechanism of action remain unclear, which limits its clinical application and the development of novel drugs. In this study, we explored key compounds, targets, and mechanisms of action for GLXB in the treatment of CHD using the network pharmacology approach. We identified 18 compounds and 21 action targets via database screening. Enrichment analysis indicated that the effects of GLXB in patients with CHD are primarily associated with the regulation of signalling pathways for tumour necrosis factor, nuclear factor-kappa B, hypoxia-inducible factor-1, arachidonic acid metabolism, and insulin resistance. GLXB thus exerts anti-inflammatory, antihypoxic, and antiagglutinating effects; regulates lipid metabolism; and combats insulin resistance in CHD via these pathways, respectively. After reverse targeting, we observed that the main active compounds of GLXB in the treatment of CHD were quercetin, naringenin, ß-sitosterol, ethyl linolenate, ethyl linoleate, and prostaglandin B1. To explore the potential of these compounds in the treatment of CHD, we verified the affinity of the compounds and targets via molecular docking analysis. Our study provides a bridge for the transformation of natural herbs and molecular compounds into novel drug therapies for CHD.

3.
Biomed Pharmacother ; 143: 112133, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34474337

RESUMO

MCC950, an NLRP3 inflammasome inhibitor, displays multiple pharmacological properties. However, the protective potential and underlying mechanism of MCC950 against doxorubicin (DOX)-induced myocardial injury has not been well investigated yet. Herein, DOX-induced myocardial injury in mice and in H9c2 myocardial cells was investigated, and the protective effects and underlying mechanism of MCC950 were fully explored. The results showed that MCC950 co-treatment significantly improved myocardial function, inhibited inflammatory and myocardial fibrosis, and attenuated cardiomyocyte pyroptosis in DOX-treated mice. Mechanismly, MCC950 had the potential to inhibit DOX-induced the cleavage of NLRP3, ASC, Caspase-1, IL-18, IL-1ß and GSDMD in vivo. Moreover, MCC950 co-treatment in vivo suppressed DOX-induced cytotoxicity as well as inflammatory and cardiomyocyte pyroptosis through the same molecular mechanism. Taken together, our findings validated that MCC950, an NLRP3 inflammasome inhibitor, has the potential to attenuate doxorubicin-induced myocardial injury in vivo and in vitro by inhibiting NLRP3-mediated pyroptosis.

4.
FEBS Open Bio ; 11(11): 2966-2976, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34407320

RESUMO

Myocardial infarction (MI) is caused by the formation of plaques in the arterial walls, leading to a decrease of blood flow to the heart and myocardium injury as a result of hypoxia. Ferroptosis is a crucial event in myocardial injury, and icariin (ICA) exerts protective effects against myocardial injury. Here, we investigated the protective mechanism of ICA in hypoxia/reoxygenation (H/R)-induced ferroptosis of cardiomyocytes. H9C2 cells were subjected to H/R induction. The content of lactate dehydrogenase and the levels of oxidative stress and intracellular ferrous ion Fe2+ were measured. The levels of ferroptosis markers (ACSL4 and GPX4) were detected. H/R-induced H9C2 cells were cultured with ICA in the presence or absence of ferroptosis inducer (erastin). Znpp (an HO-1 inhibitor) was added to ICA-treated H/R cells to verify the role of the Nrf2/HO-1 pathway. H/R-induced H9C2 cells showed reduced viability, enhanced oxidative stress and lactate dehydrogenase content, increased levels of Fe2+ and ACSL4, and decreased levels of GPX4. ICA inhibited H/R-induced ferroptosis and oxidative stress in cardiomyocytes. Erastin treatment reversed the inhibitory effect of ICA on ferroptosis in H/R cells. The expression of Nrf2 and HO-1 in H/R-induced H9C2 cells was reduced, whereas ICA treatment reversed this trend. Inhibition of the Nrf2/HO-1 pathway reversed the protective effect of ICA on H/R-induced ferroptosis. Collectively, our results suggest that ICA attenuates H/R-induced ferroptosis of cardiomyocytes by activating the Nrf2/HO-1 signaling pathway.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34285700

RESUMO

Radix Astragali and Semen Lepidii (HQ-TLZ) is a commonly used herbal medicine combination for treatment of heart failure, which has a good clinical effect. However, its active components and mechanism of action are not clear, which limits its clinical application and development. In this study, we explored the mechanism of action of HQ-TLZ in the treatment of heart failure based on network pharmacology. We obtained 11 active ingredients and 109 targets from the TCMSP database and SwissTargetPrediction database. Next, we constructed the action network and carried out enrichment analysis. The results showed that HQ-TLZ treatment of heart failure is primarily achieved by regulating the insulin resistance, erbB signaling pathway, PI3K-Akt signaling pathway, and VEGF signaling pathway. After inverse targeting, molecular docking, and literature search, we determined that the equivalent molecular groups of HQ-TLZ in the treatment of heart failure were quercetin and kaempferol. Based on network pharmacology, we reveal the mechanism of action of HQ-TLZ in the treatment of heart failure to a certain extent. At the same time, we determined the composition of the equivalent molecular group. This provides a bridge for the consistency evaluation of natural herbs and molecular compounds, which is beneficial to the development of novel drugs and further research.

6.
Artigo em Inglês | MEDLINE | ID: mdl-33273955

RESUMO

Fuxin mixture (FXHJ) is a prescription for the treatment of heart failure. It has been shown to be effective in clinical trials, but its active ingredients and mechanism of action are not completely clear, which limits its clinical application and international promotion. In this study, we used network pharmacology to find, conclude, and summarize the mechanism of FXHJ in the treatment of heart failure. From FXHJ, we found 39 active ingredients and 47 action targets. Next, we constructed the action network and was conducted enrichment analysis. The results showed that FXHJ mainly treated heart failure by regulating the MAPK signaling pathway, PI3KAkt signaling pathway, cAMP signaling pathway, TNF signaling pathway, toll-like receptor signaling pathway, VEGF signaling pathway, NF-kappa B signaling pathway, and the apoptotic signaling molecule BCL2. Through the research method of network pharmacology, this study summarized the preliminary experiments of the research group and revealed the probable mechanism of FXHJ in the treatment of heart failure to a certain extent, which provided some ideas for the development of new drugs.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31949473

RESUMO

Objective: Heart failure is a major public health problem worldwide nowadays. However, the morbidity, mortality, and awareness of heart failure are not satisfied as well as the status of current treatments. According to the standard treatment for chronic heart failure (CHFST), Fuzi (the seminal root of Aconitum carmichaelii Debx.) formulae are widely used as a complementary treatment for heart failure in clinical practice for a long time. We are aiming to assess the efficacy and safety of Fuzi formulae (FZF) on the treatment of heart failure according to high-quality randomized controlled trials (RCTs). Methods: RCTs in PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Chinese Scientific Journals Database (VIP), and Wanfang Database were searched from their inception until June 2019. In addition, the U.S. National Library of Medicine (clinicaltrials.gov) and the Chinese Clinical Trial Registry (http://www.chictr.org.cn) were also searched. We included RCTs that test the efficacy and safety of FZF for the treatment of heart failure, compared with placebo, CHFST, or placebo plus CHFST. The methodological quality of included studies were evaluated by the Cochrane Collaboration's tool for assessing risk of bias. RCTs with Cochrane risk of bias (RoB) score ≥4 were included in the analysis. The meta-analysis was conducted through RevMan 5.2 software. The GRADE approach was used to assess the quality of the evidence. Results: Twelve RCTs with 1490 participants were identified. The studies investigated the efficacy and safety of FZF, such as FZF plus the CHFST vs placebo plus CHFST (n = 4), FZF plus CHFST vs CHFST (n = 6), FZF plus digoxin tablets (DT) plus CHFST vs placebo plus DT plus CHFST (n = 1), and FZF plus placebo plus CHFST vs placebo plus DT plus CHFST (n = 1). Meta-analysis indicated that FZF have additional benefits based on the CHFST in reducing plasma NT-proBNP level, MLHFQ scores, Lee's heart failure scores (LHFs), and composite cardiac events (CCEs). Meanwhile, it also improved the efficacy on TCM symptoms (TCMs), NYHA functional classification (NYHAfc), 6MWD, and LVEF. Adverse events were reported in 6 out of 12 studies without significant statistical difference. However, after assessing the strength of evidence, it was found that only the quality of evidence for CCEs was high, and the others were either moderate or low or very low. So we could not draw confirmative conclusions on its additional benefits except CCEs. Further clinical trials should be well designed to avoid the issues that were identified in this study. Conclusion: The efficacy and additional benefits of FZF for CCEs were certain according to the high-quality evidence assessed through GRADE. However, the efficacy and additional benefits for the other outcomes were uncertain judging from current studies. In addition, the safety assessment has a great room for improvement. Thus, further research studies are needed to find more convincing proofs.

8.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 37(4): 453-457, 2017 04.
Artigo em Chinês | MEDLINE | ID: mdl-30650505

RESUMO

Objective To observe the effect of Fuxin Mixture(FXM) on the ß,-AR(adrenergic receptor) -cAMP(cyclic adenosine monophosphate, cAMP) -PKA ( protein kinase A, PKA) pathway of rats with heart failure. Methods Male Wistar rats were randomly divided into blank control group, captopril group, FXM low dose group, FXM high dose group and model group.Models of CHF were established. After drug intervention for 6 weeks, the left ventricular mass index (LVMI) was analysed, the expression of ß1 - AR mRNA in myocardial tissue was measured,the level of cAMP in rat plasma,the OD value PKA content of spleen tissue homogenate were detected. Results Compared with the blank control group, the LVMI and the cAMP in plasma of model group were increased (P <0. 05), the expression of ß1,-AR mRNA, the OD value of spleen tissue homogenate and PKA were decreased (P <0. 01). Compared with the model group, the LVMI were decreased,and the expression of ß1-AR mRNA were increased in FXM high dose group and captopril group (P <0. 01 , P <0. 05) ; the level of cAMP in plasma of each drug group were decreased (P <0. 01) , the OD value of spleen tissue homogenate and PKA were increased (P <0. 01). Compared with the captopril group, the expression of ß1-AR mRNA, the OD value of spleen tissue homogenate and PKA were decreased, and the LVMI and the cAMP were increased in the FXM low dose group (P <0. 01 , P <0. 05). Compared with the FXM low dose group, the LVMI and the cAMP of FXM high dose group were decreased (P <0. 05), the expression of ß1-AR mRNA, the OD value of spleen tissue homogenate and PKA were increased (P <0. 01). Conclusion FXM could play the role of anti-heart fail- ure through regulating P1-AR-cAMP-PKA pathway.


Assuntos
Proteínas Quinases Dependentes de AMP Cíclico , Medicamentos de Ervas Chinesas , Insuficiência Cardíaca , Animais , AMP Cíclico , Proteínas Quinases Dependentes de AMP Cíclico/efeitos dos fármacos , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Masculino , Miocárdio , Distribuição Aleatória , Ratos , Ratos Wistar
9.
Clin Res Cardiol ; 104(4): 310-9, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25391292

RESUMO

Chronic stress is a known risk factor for both endothelial dysfunction and cardiovascular disease (CVD), but less is known of how acute mental stress affects the vasculature. In this systematic review and meta-analysis, we analyzed the impact of acute mental stress on flow-mediated dilation (FMD), an indicator of endothelial function. We searched the Medline, Cochrane, EMBASE, and ISI Web of Knowledge databases through May 2014, to identify publications in English-language journals. The primary outcome was the change in FMD from baseline to the time of measurement. We also assessed the risk of bias and the heterogeneity of included studies. Our search identified eight prospective studies, which displayed significant heterogeneity. Four studies measured FMD while the subject was performing the task; six measured FMD after the task had been completed. The total number of participants was 164. The pooled results indicate that FMD did not change significantly while the task was being performed (pooled difference in means: -0.853; 95 % confidence interval (CI), -3.926/2.220; P = 0.586); however, FMD measured after the task was completed was significantly less than baseline (pooled difference in means: -2.450; 95 %CI, -3.925/-0.975; P = 0.001). In conclusions, our findings provide evidence that an acute stressful experience has a delayed, negative impact on the function of the endothelium. Repeated exposure to short-term stress may lead to permanent injury of the vasculature. Therefore, assessment of patients' exposure to both repeated acute mental stress and chronic stress may be useful in determining their risk of developing CVD.


Assuntos
Estresse Psicológico/epidemiologia , Estresse Psicológico/prevenção & controle , Disfunção Ventricular Esquerda/epidemiologia , Disfunção Ventricular Esquerda/prevenção & controle , Doença Aguda , Adulto , Idoso , Causalidade , Comorbidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Medição de Risco , Estresse Psicológico/psicologia , Resultado do Tratamento , Disfunção Ventricular Esquerda/psicologia , Adulto Jovem
10.
Heart Lung Circ ; 22(4): 291-6, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23261325

RESUMO

AIMS: We tested whether anger affects the balance between endothelium-derived vasodilators and vasoconstrictors in spontaneously hypertensive rats (SHRs). METHODS: Five endothelium-produced vasoactive factors (nitric oxide, prostacyclin, urotensin, endothelin and thromboxane B2) were measured in an established SHR behavioural model of anger, in "non-angry" SHR rats, and in control Wistar-Kyoto rats. RESULTS: All angry SHR rats showed the typical angry behaviour and angry SHR rats had significantly higher blood pressure and heart rate than control rats. Angry rats had significantly lower levels of two vasodilators, nitric oxide and prostacyclin, and significantly higher levels of two vasoconstrictors, endothelin and thromboxane B2 than either non-angry SHR or control rats. Levels of a third vasoconstrictor, urotensin, were significantly lower in angry SHR than in non-angry SHR or control rats. CONCLUSIONS: Our results suggest that anger causes an imbalance of endothelium-produced vasodilating and vasoconstricting substances. This may have implications for the development and/or progression of hypertension.


Assuntos
Ira , Comportamento Animal , Pressão Sanguínea , Endotélio Vascular , Vasoconstritores/sangue , Animais , Endotelinas/sangue , Endotélio Vascular/metabolismo , Endotélio Vascular/fisiopatologia , Epoprostenol/sangue , Masculino , Óxido Nítrico/sangue , Ratos , Ratos Endogâmicos SHR , Tromboxano B2/sangue , Urotensinas/sangue
11.
Zhongguo Zhong Xi Yi Jie He Za Zhi ; 31(2): 191-4, 2011 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-21425572

RESUMO

OBJECTIVE: To observe the clinical effects and safety of Xiongshao Capsule (XSC) in treating patients with coronary heart disease angina of Xin-blood stasis syndrome. METHODS: Two hundred and forty patients were randomized equally into two groups, the treatment group and control group. They were treated with XSC and Xuefu Zhuyu Capsule respectively for 4 weeks. The therapeutic effect on angina pectoris, the dosage of nitroglycerin used and its withdrawal rate were observed, and changes in Chinese medical syndrome, electrocardiogram (ECG), blood lipids, and hemorrheologic figure were observed before and after treatment. RESULTS: The favorable effects on angina pectoris, ECG, Chinese medical syndromes, and clinical symptoms were observed in the treatment groups, showing significant statistical difference in improving angina pectoris and ECG to the control group (P < 0.05 or P < 0.01). CONCLUSION: XSC was effective and safe in treating coronary heart disease angina of Xin-blood stasis syndrome.


Assuntos
Angina Pectoris/tratamento farmacológico , Doença das Coronárias/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Fitoterapia , Adulto , Idoso , Angina Pectoris/diagnóstico , Cápsulas , Método Duplo-Cego , Feminino , Humanos , Masculino , Medicina Tradicional Chinesa , Pessoa de Meia-Idade , Resultado do Tratamento
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