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1.
Medicine (Baltimore) ; 99(15): e19648, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32282713

RESUMO

BACKGROUND: Xingnaojing injection (XNJi) is widely used for acute cerebral hemorrhage. However, the efficacy of XNJi for acute cerebral hemorrhage has not been comprehensively proved by systematic analysis yet. Therefore, it is essential to evaluate the efficacy and safety of XNJi in an evidence-based method. METHODS: Six databases were searched with XNJi used for acute cerebral hemorrhage in randomized controlled trials (RCTs). Meta-analysis was performed by Review Manager 5.3. The efficacy rate, brain edema, cerebral hematoma, neurological deficit score, hs-crp, Glasgow Coma Scale (GCS), and activities of daily living (ADL) were systematically evaluated. The Cochrane risk of bias was used to evaluate the methodological quality of eligible studies. RESULTS: This study is registered with PROSPERO (CRD42018098737). Twenty-nine studies with a total of 2638 patients were included in this meta-analysis. Compared with conventional treatment, XNJi got higher efficacy rate (OR = 3.37, 95% CI [2.65, 4.28], P < .00001). Moreover, XNJi showed significant enhancement of efficacy rate via subgroup analysis in course and dosage. In addition, XNJi demonstrated significant improvement in Chinese stroke scale (CSS) and National Institutes of Health Stroke Scale (NHISS) (mean difference [MD] = -4.74, 95% CI [-5.89, -3.60], P < .00001; MD = -4.45, 95% CI [-5.49, -3.41], P < .00001), GCS (MD = 2.72, 95% CI [2.09, 3.35], P < .00001). It also remarkably decreased the level of hs-crp (MD = -6.50, 95% CI [-7.79, -5.21], P < .00001), enhanced ADL (MD = 20.38, 95% CI [17.98, 22.79], P < .00001), and alleviated hematoma and edema (MD = -2.53, 95% CI [-4.75, -0.31] P < .05; MD = -1.74 95% CI [-2.42, -1.07] P < .00001) compared with conventional treatment. CONCLUSION: XNJi is effective in treating acute cerebral hemorrhage with significant improvement of CSS, NHISS and impairment of hs-crp, hematoma, and edema compared with conventional treatment. Moreover, XNJi got remarkable efficacy at the dose of 20, 30, 60 mL and from 7 to 28 days. No serious adverse reactions occurred. These results were mainly based on small-sample and low-quality studies. Therefore, more rigorous, large-scale RCTs were further needed to confirm its efficacy, safety, and detailed characteristic of application.


Assuntos
Hemorragia Cerebral/tratamento farmacológico , Medicamentos de Ervas Chinesas/administração & dosagem , Atividades Cotidianas , Doença Aguda , Adulto , Idoso , Idoso de 80 Anos ou mais , Edema Encefálico/epidemiologia , Proteína C-Reativa/análise , Proteína C-Reativa/efeitos dos fármacos , Hemorragia Cerebral/epidemiologia , Medicamentos de Ervas Chinesas/efeitos adversos , Medicamentos de Ervas Chinesas/uso terapêutico , Feminino , Escala de Coma de Glasgow/estatística & dados numéricos , Hematoma , Humanos , Injeções , Masculino , Pessoa de Meia-Idade , Doenças do Sistema Nervoso/epidemiologia , Doenças do Sistema Nervoso/fisiopatologia , Ensaios Clínicos Controlados Aleatórios como Assunto
2.
J Cell Mol Med ; 24(7): 4036-4050, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32073745

RESUMO

Higenamine (HG) is a natural benzylisoquinoline alkaloid isolated from Aconitum with positive inotropic and chronotropic effects. This study aimed to investigate the possible cardioprotective effects of HG combined with [6]-gingerol (HG/[6]-GR) against DOX-induced chronic heart failure (CHF) by comprehensive approaches. DOX-induced cardiotoxicity model in rats and H9c2 cells was established. Therapeutic effects of HG/[6]-GR on haemodynamics, serum indices and histopathology of cardiac tissue were analysed. Cell mitochondrial energy phenotype and cell mitochondrial fuel flex were measured by a Seahorse XFp analyser. Moreover, UHPLC-Q-TOF/MS was performed to explore the potential metabolites affecting the therapeutic effects and pathological process of CHF. To further investigate the potential mechanism of HG/[6]-GR, mRNA and protein expression levels of RAAS and LKB1/AMPK/Sirt1-related pathways were detected. The present data demonstrated that the therapeutic effects of HG/[6]-GR combination on CHF were presented in ameliorating heart function, down-regulation serum indices and alleviating histological damage of heart tissue. Besides, HG/[6]-GR has an effect on increasing cell viability of H9c2 cells, ameliorating DOX-induced mitochondrial dysfunction and elevating mitochondrial OCR and ECAR value. Metabolomics analyses showed that the therapeutic effect of HG/[6]-GR combination is mainly associated with the regulation of fatty acid metabolites and energy metabolism pathways. Furthermore, HG/[6]-GR has an effect on down-regulating RAAS pathway-related molecules and up-regulating LKB1/AMPKα/Sirt1-related pathway. The present work demonstrates that HG/[6]-GR prevented DOX-induced cardiotoxicity via the cardiotonic effect and promoting myocardial energy metabolism through the LKB1/AMPKα/Sirt1 signalling pathway, which promotes mitochondrial energy metabolism and protects against CHF.

3.
Phytother Res ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-32026542

RESUMO

Cholestasis is a common manifestation of decreased bile flow in various liver diseases. It results in fibrosis and even cirrhosis without proper treatment. It is believed that a wide range of factors, including transporter dysfunction, oxidative stress, inflammatory damage, and immune disruption, can cause cholestasis. In recent years, natural products have drawn much attention for specific multiple-target activities in diseases. Many attempts have been made to investigate the anticholestatic effects of natural products with advanced technology. This review summarizes recent studies on the biological activities and mechanisms of recognized compounds for cholestasis treatment. Natural products, including various flavonoids, phenols, acids, quinones, saponins, alkaloids, glycosides, and so on, function as comprehensive regulators via ameliorating oxidative stress, inflammation, and apoptosis, restoring bile acid balance with hepatic transporters, and adjusting immune disruption. Moreover, in this progress, nuclear factor erythroid 2-related factor 2, reactive oxygen species production, heme oxygenase-1, NF-κB, cholesterol 7 alpha-hydroxylase, and farnesoid X receptors are thought as main targets for the activity of natural products. Therefore, this review presents the detailed mechanisms that include multiple targets and diverse signalling pathways. Natural products are the valuable when seeking novel therapeutic agents to treat cholestatic liver diseases.

4.
Life Sci ; 248: 117456, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32097666

RESUMO

AIMS: In this study, we will investigate the therapeutic effects of berberine (BBR) in Helicobacter pylori (H. pylori) induced chronic atrophic gastritis (CAG). Furthermore, potential mechanisms of BBR in regulating IRF8-IFN-γ signaling axis will also be investigated. MATERIALS AND METHODS: H. pylori were utilized to establish CAG model of rats. Therapeutic effects of BBR on serum supernatant indices, and histopathology of stomach were analyzed in vivo. Moreover, GES-1 cells were infected by H. pylori, and intervened with BBR in vitro. Cell viability, morphology, proliferation, and quantitative analysis were detected by high-content screening (HCS) imaging assay. To further investigate the potential mechanisms of BBR, relative mRNA, immunohistochemistry and protein expression in IRF8-IFN-γ signaling axis were measured. KEY FINDINGS: Results showed serum supernatant indices including IL-17, CXCL1, and CXCL9 were downregulated by BBR intervention, while, G-17 increased significantly. Histological injuries of gastric mucosa induced by H. pylori also were alleviated. Moreover, cell viability and morphology changes of GES-1 cells were improved by BBR intervention. In addition, proinflammatory genes and IRF8-IFN-γ signaling axis related genes, including Ifit3, Upp1, USP18, Nlrc5, were suppressed by BBR administration in vitro and in vivo. The proteins expression related to IRF8-IFN-γ signaling axis, including Ifit3, IRF1 and Ifit1 were downregulated by BBR intervention.


Assuntos
Anti-Inflamatórios/farmacologia , Berberina/farmacologia , Gastrite Atrófica/tratamento farmacológico , Infecções por Helicobacter/tratamento farmacológico , Fatores Reguladores de Interferon/genética , Interferon gama/genética , Animais , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Quimiocina CXCL1/antagonistas & inibidores , Quimiocina CXCL1/genética , Quimiocina CXCL1/imunologia , Quimiocina CXCL9/antagonistas & inibidores , Quimiocina CXCL9/genética , Quimiocina CXCL9/imunologia , Doença Crônica , Modelos Animais de Doenças , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/imunologia , Células Epiteliais/microbiologia , Gastrite Atrófica/genética , Gastrite Atrófica/imunologia , Gastrite Atrófica/microbiologia , Regulação da Expressão Gênica , Infecções por Helicobacter/genética , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/microbiologia , Helicobacter pylori/efeitos dos fármacos , Helicobacter pylori/crescimento & desenvolvimento , Helicobacter pylori/patogenicidade , Humanos , Fatores Reguladores de Interferon/antagonistas & inibidores , Fatores Reguladores de Interferon/imunologia , Interferon gama/antagonistas & inibidores , Interferon gama/imunologia , Interleucina-17/agonistas , Interleucina-17/genética , Interleucina-17/imunologia , Masculino , Proteínas NLR/antagonistas & inibidores , Proteínas NLR/genética , Proteínas NLR/imunologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Uridina Fosforilase/antagonistas & inibidores , Uridina Fosforilase/genética , Uridina Fosforilase/imunologia
5.
J Pharm Pharmacol ; 72(2): 279-293, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31743450

RESUMO

OBJECTIVES: This study was aimed to explore the mechanism of Aconiti Lateralis Radix Praeparata (ALRP) and Zingiberis Rhizoma (ZR) on doxorubicin (DOX)-induced chronic heart failure (CHF) in rats by integrated approaches. METHODS: Effects of ALRP and ZR on cardiac function, serum biochemical indicators and histopathology in rats were analysed. Moreover, UHPLC-Q-TOF/MS was performed to identify the potential metabolites affecting the pathological process of CHF. Metabolomics and network pharmacology analyses were conducted to illustrate the possible pathways and network in CHF treatment. The predicted gene expression levels in heart tissue were verified and assessed by RT-PCR. KEY FINDINGS: ALRP-ZR demonstrated remarkable promotion of hemodynamic indices and alleviated histological damage of heart tissue. Metabolomics analyses showed that the therapeutic effect of ALRP and ZR is mainly associated with the regulation of eight metabolites and ten pathways, which may be responsible for the therapeutic efficacy of ALRP-ZR. Moreover, the results of RT-PCR showed that ALRP-ZR could substantially increase the expression level of energy metabolism-related genes, including PPARδ, PPARγ, Lpl, Scd, Fasn and Pla2g2e. CONCLUSIONS: The results highlighted the role of ALRP-ZR in the treatment of CHF by influencing the metabolites related to energy metabolism pathway via metabolomics and network pharmacology analyses.

6.
Front Pharmacol ; 10: 1135, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31680945

RESUMO

Backgrounds: Salsolinol (SAL), a plant-based isoquinoline alkaloid, was initially isolated from Aconiti Lateralis Radix Praeparata (ALRP) and identified as the active cardiotonic component of ALRP. This study was aimed to explore the therapeutic effect and mechanism by which SAL attenuates doxorubicin (DOX)-induced chronic heart failure (CHF) in rats and improves mitochondrial function in H9c2 cardiomyocytes. Methods: Rats were intraperitoneally injected with DOX to establish CHF model. Therapeutic effects of SAL on hemodynamic parameters, serum indices, and the histopathology of the heart were analyzed in vivo. Moreover, H9c2 cardiomyocytes were pretreated with SAL for 2 h before DOX treatment in all procedures in vitro. Cell viability, cardiomyocyte morphology, proliferation, and mitochondrial function were detected by a high-content screening (HCS) assay. In addition, a Seahorse Extracellular Flux (XFp) analyzer was used to evaluate the cell energy respiratory and energy metabolism function. To further investigate the potential mechanism of SAL, relative mRNA and protein expression of key enzymes in the tricarboxylic acid cycle in vivo and mitochondrial calcium uniporter (MCU) signaling pathway-related molecules in vitro were detected. Results: The present data demonstrated the pharmacological effect of SAL on DOX-induced CHF, which was through ameliorating heart function, downregulating serum levels of myocardial injury markers, alleviating histological injury to the heart, increasing the relative mRNA expression levels of key enzymes downstream of the tricarboxylic acid cycle in vivo, and thus enhancing myocardial energy metabolism. In addition, SAL had effects on increasing cell viability, ameliorating DOX-induced mitochondrial dysfunction, and increasing mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) in H9c2 cardiomyocyte. Moreover, we found that SAL might have an effect on improving mitochondrial respiratory function and energy metabolism via inhibiting excessive activation of MCU pathway in H9c2 cells. However, the protective effect could be ameliorated by ruthenium red (an MCU inhibitor) and abrogated by spermine (an MCU activator) in vitro. Conclusion: The therapeutic effects of SAL on CHF are possibly related to ameliorating cardiomyocyte function resulting in promotion of mitochondrial respiratory and energy metabolism. Furthermore, the potential mechanism might be related to downregulating MCU pathway. These findings may provide a potential therapy for CHF.

8.
J Ethnopharmacol ; 238: 111880, 2019 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-31004728

RESUMO

BACKGROUND: The combined use of Aconiti Lateralis Radix Praeparata (ALRP) and Zingiberis Rhizoma (ZR) are classic compatibilities in China for the treatment of cardiovascular diseases such as increasing myocardial contractility, anti-arrhythmia, reducing myocardial oxygen consumption, and dilating organ blood vessels, etc, thereby exerting anti-heart failure (HF) effects in traditional Chinese herbal medicine. However, comprehensive approaches for understanding the therapeutic effects and mechanisms underlying chronic heart failure (CHF) from the perspective of energy metabolism have not been pursued. AIM: This research was aimed to investigate the effectiveness and potential mechanism of ALRP combined with ZR (1:1) on doxorubicin (DOX)-induced CHF in rats based on an integrated approach that combines network pharmacology analyses and molecular biology. MATERIAL AND METHODS: CHF model was established by the intraperitoneal injection of DOX. ALRP and ZR were intragastrically administrated for three weeks. The detection indices including hemodynamic measurements, myocardial injury marker, and myocardial pathological changes were measured. Network pharmacology analysis was used to illustrate the pathways and network of ALRP and ZR against HF. Mitochondrial energy metabolism pathway associated gene and protein levels of PPARα, PGC-1α and Sirt3 in myocardial tissue were detected by real-time PCR and western blotting, respectively. RESULTS: The results indicated that ALRP-ZR herbal couple significantly improved the left ventricular function and cardiac enzyme activities in comparison with their single use. Network pharmacology analysis results showed that the pharmacological mechanisms of ALRP-ZR may be related to PPAR energy metabolism pathway. Besides, the outcomes of western-blot and real-time PCR analysis showed that ALRP-ZR significantly upregulates the protein and gene level of PPARα, PGC-1α, and Sirt3. CONCLUSIONS: Network pharmacology analysis would be an effective network analyze workflow which was feasible for evaluating the pharmacological effect of a multi-drug complex system. The Chinese herbal couple ALRP-ZR had a better therapeutic effect than their single-use against DOX-induced CHF, which may be related to enhancing left ventricular function by activating the PPARα/PGC-1α/Sirt3 pathway.


Assuntos
Aconitum/química , Doxorrubicina/toxicidade , Insuficiência Cardíaca/induzido quimicamente , Rizoma/química , Zingiberaceae/química , Animais , Biomarcadores , Medicamentos de Ervas Chinesas/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Insuficiência Cardíaca/prevenção & controle , Masculino , PPAR alfa/genética , PPAR alfa/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , RNA Mensageiro , Ratos , Ratos Sprague-Dawley , Sirtuínas/genética , Sirtuínas/metabolismo , Inibidores da Topoisomerase II/toxicidade
9.
Biomed Pharmacother ; 115: 108881, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31028997

RESUMO

Higenamine (HG) is a well-known selective activator of beta2-adrenergic receptor (ß2-AR) with a positive inotropic effect. The present study showed that HG combined with [6]-gingerol (HG/[6]-GR) protects H9c2 cells from doxorubicin (DOX)-induced mitochondrial energy metabolism disorder and respiratory dysfunction. H9c2 cells were pretreated with HG/[6]-GR for 2 h before DOX treatment in all procedures. Cell viability was quantified by a cell counting kit­8 assay. Cardiomyocyte morphology, proliferation, and mitochondrial function were detected by a high content screening (HCS) assay. Cell mitochondrial stress was measured by a Seahorse XFp analyzer. To further investigate the protective mechanism of HG/[6]-GR, mRNA and protein expression levels of PPARα/PGC-1α/Sirt3 pathway-related molecules were detected. The present data demonstrated that protective effects of HG/[6]-GR combination were presented in mitochondria, which increased cell viability, ameliorated DOX-induced mitochondrial dysfunction, increased mitochondrial oxygen consumption rate (OCR) and extracellular acidification rate (ECAR). Most importantly, the protective effects were abrogated by GW6471 (a PPARα inhibitor) and ameliorated by Wy14643 (a PPARα agonist). Moreover, the combined use of HG and [6]-GR exerted more profound protective effects than either drug as a single agent. In conclusion, the results suggested that HG/[6]-GR ameliorates DOX-induced mitochondrial energy metabolism disorder and respiratory function impairment in H9c2 cells, and it indicated that the protective mechanism may be related to upregulation of the PPARα/PGC-1α/Sirt3 pathway, which promotes mitochondrial energy metabolism and protects against heart failure.


Assuntos
Alcaloides/farmacologia , Catecóis/farmacologia , Doxorrubicina/toxicidade , Álcoois Graxos/farmacologia , Mitocôndrias/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Tetra-Hidroisoquinolinas/farmacologia , Translocador 1 do Nucleotídeo Adenina/genética , Translocador 1 do Nucleotídeo Adenina/metabolismo , Agonistas Adrenérgicos beta/administração & dosagem , Agonistas Adrenérgicos beta/farmacologia , Alcaloides/administração & dosagem , Animais , Antibióticos Antineoplásicos/toxicidade , Catecóis/administração & dosagem , Linhagem Celular , Sobrevivência Celular , Metabolismo Energético/efeitos dos fármacos , Álcoois Graxos/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , PPAR alfa/genética , PPAR alfa/metabolismo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Sirtuínas/genética , Sirtuínas/metabolismo , Tetra-Hidroisoquinolinas/administração & dosagem , Fatores de Transcrição de p300-CBP/genética , Fatores de Transcrição de p300-CBP/metabolismo
10.
Artigo em Inglês | MEDLINE | ID: mdl-30581490

RESUMO

Objectives: Cerebral ischemia can cause severe harm to people's health with the characteristics of high incidence, high disability, and high mortality. Xingnaojing injection (XNJI) is widely used in the treatment of cerebral ischemia. The aim of this review is to evaluate the efficacy and mechanism of XNJI in animal models of cerebral ischemia. Methods: Total seven electronic databases in English or Chinese (CNKI, Wanfang, VMIS, PubMed, MEDLINE, Embase, and the Cochrane Library) about most experiments and studies which came out before June 2018 of XNJI for cerebral ischemia have been searched. Data extraction, quality assessment, and meta-analysis are conducted according to the Cochrane standards and RevMan 5.3 software. Results: We have identified 23 eligible studies and made a meta-analysis based on these studies. Meta-analysis shows that XNJI contributes significantly to reduction in neurological deficit score (P = 0.0002, MD = -1.25, 95% CI: -1.92, -0.58) compared with the control group of cerebral ischemia. Subgroup analytic results demonstrate that XNJI has been more effective in animal model of cerebral ischemia-reperfusion injury (P = 0.009, MD = -1.35, 95%CI: -2.36, -0.34) than that of permanent cerebral ischemia (P = 0.0002, MD = -1.08, 95%CI: -1.66, -0.51). Compared with control group, XNJI could remarkably reduce cerebral infarction area (P < 0.00001, MD = -14.98, 95%CI: -21.36, -8.59), brain edema (P < 0.00001, MD = -4.64, 95%CI: -5.38, -3.90), and neuronal cell apoptosis (P < 0.0001, MD = -12.21, 95%CI: 18.05, -6.37). Meanwhile, the meta-analysis shows that XNJI has a significant anti-inflammatory effect, and the levels of TNF-α, IL-6, and IL-1ß are significantly reduced by XNJI (P = 0.001, MD = -4.13, 95%CI:-6.68, -1.58; P < 0.00001, MD = -119.23, 95%CI: -138.04, -100.43; P = 0.21, MD = -228.69, 95% CI: -586.20, 128.83). Additionally, XNJI could raise the body's antioxidant function and the level of SOD and GSH-Px (P = 0.002, MD = 53.02, 95% CI: -20.52, 85.78; P = 0.01, MD = 8.65, 95% CI: 1.77, 15.48) and decrease the level of MDA (P < 0.00001, MD = -4.16, 95% CI: -5.50, -2.82). Conclusion: XNJI might be effective in cerebral ischemia by regulating oxidative stress and inflammatory reaction.

11.
Medicine (Baltimore) ; 97(51): e13580, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30572460

RESUMO

BACKGROUND: Shexiang Baoxin Pill (SBP) is one of the most commonly used traditional Chinese patent medicines for cardiovascular diseases. This systematic review was designed to provide rigorous therapeutic efficacy and safety evidence on the use of SBP combined with trimetazidine in elderly patients with heart failure (HF) secondary to ischaemic cardiomyopathy (ICM). METHODS: Relevant randomized controlled trials (RCTs) investigating the clinical efficacy of SBP combined with trimetazidine in treating ICM-associated HF were widely searched in electronic databases, including PubMed, Cochrane library, EMBASE, CBM, CNKI, VMIS, and Wanfang up to January 1, 2018. The methodological quality of each trial was assessed according to the Cochrane Reviewers' Handbook 5.0. Meta-analysis was performed by using Review Manager 5.3. RESULTS: Eighteen RCTs (N = 1532) that met the criteria were included in the review for the assessment of methodological quality. Meta-analysis showed that, when compared with conventional therapy, SBP combined with trimetazidine significantly improved the clinical efficacy and indices of cardiac function (including increasing left ventricular ejection fraction [LVEF] and 6-minute walk distance [6-MWD], decreasing left ventricular end-diastolic diameter [LVEDD] and left ventricular end-systolic diameter [LVESD]) without serious adverse reactions. CONCLUSION: This work provides evidence of the benefit of SBP combined with trimetazidine for the treatment of HF secondary to ICM. More high quality and well-designed RCTs are needed to confirm these findings.


Assuntos
Fármacos Cardiovasculares/uso terapêutico , Medicamentos de Ervas Chinesas/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/etiologia , Isquemia Miocárdica/complicações , Trimetazidina/uso terapêutico , Quimioterapia Combinada , Humanos , Isquemia Miocárdica/tratamento farmacológico , Ensaios Clínicos Controlados Aleatórios como Assunto
12.
J Pharm Pharmacol ; 70(12): 1675-1687, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30277564

RESUMO

OBJECTIVES: Cholestasis is a critical risk factor for severe hepatic disease or cirrhosis. The anti-inflammatory effect of Paeonia lactiflora Pall. (PLP), named Chishao in traditional Chinese medicine (TCM), on alpha-naphthylisothiocyanate (ANIT)-induced cholestasis model was tried to be elucidated in this research. METHODS: Therapeutic effect indices on hepatic function, including ALT, AST, TBIL, DBIL, ALP, TBA and γ-GT, were measured. To further investigate the protective mechanism of PLP, the mRNA and protein expression levels of NF-κB-NLRP3 inflammasome pathway were detected. RESULTS: Our results showed that compared with the model group, PLP could significantly reduce the increased serum indices such as ALT, AST, TBIL, DBIL, ALP, TBA and γ-GT induced by ANIT in a dose-dependent way. Moreover, we found that PLP downregulated the mRNA expression levels including IKK, p65, NLRP3, caspase-1 and IL-1ß, especially at the large dose. Furthermore, PLP also significantly inhibited NF-κB-NLRP3 inflammasome pathway by decreasing the protein levels of p65, p-p65, p-IKK, NLRP3, caspase-1 and IL-1ß. CONCLUSIONS: The results indicated that PLP could ameliorate ANIT-induced cholestasis in rats and the anti-inflammatory effect of PLP might be related to regulating NF-κB-NLRP3 inflammasome pathway. This study will provide scientific evidence for PLP as a potential drug candidate for cholestasis.


Assuntos
Inflamassomos/efeitos dos fármacos , Mediadores da Inflamação/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , NF-kappa B/biossíntese , Paeonia , Extratos Vegetais/farmacologia , 1-Naftilisotiocianato/farmacologia , Animais , Biomarcadores , Colestase/induzido quimicamente , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Expressão Gênica , Humanos , Testes de Função Hepática , Medicina Tradicional Chinesa , RNA Mensageiro , Ratos , Ratos Sprague-Dawley
13.
Front Pharmacol ; 9: 810, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30140225

RESUMO

Background: Chronic heart failure (CHF) is one of the most stubborn cardiovascular disease. Xinmailong (XML), a bioactive fraction extracted from Periplaneta americana L., has been commonly used for CHF treatment in China. However, there is few comprehensive evaluation for the clinical efficacy and safety of XML for CHF. Objectives: We aimed to evaluate the beneficial and adverse effects of Xinmailong Injection (XMLI) on CHF treatment with the use of meta-analysis. Methods: In accordance with the Cochrane Handbook and transparent reporting of systematic reviews and meta-analysis protocol (CRD42018087091), seven English and Chinese electronic databases, including PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure (CNKI), Wanfang database, VIP medicine information system and China Biomedical Literature Database (CBM), were searched to retrieve potential randomized controlled trials (RCTs) before November 2017. The eligible trials were evaluated for methodological quality. The main outcome measures were analyzed with RevMan 5.3 software. Results: 26 RCTs involving 3447 participants were subjected to meta-analysis. The total effective rate was improved by XMLI plus conventional therapy (OR 3.10, 95% CI 2.47-3.90, P < 0.00001). When compared to the conventional treatment alone, the combination of XMLI and conventional treatment increased left ventricular ejection fraction (LVEF, MD 4.93, 95% CI 3.96-5.89, P < 0.00001) and 6-min walking distance (6-MWD, MD 46.76, 95% CI 32.51 to 61.01, P < 0.00001), and decreased left ventricular end-diastolic diameter (LVEDD, MD -4.73, 95% CI-5.64 to-3.83, P < 0.00001), serum brain natriuretic peptide (BNP, MD -149.59, 95% CI -211.31 to -87.88, P < 0.00001) and N-terminal pro-brain natriuretic peptide (NT-proBNP, MD -322.35, 95% CI -517.87 to -126.83, P = 0.001). However, the frequency and severity of adverse effects was similar between these two different medications. Poor methodological quality and the limitations also existed in this study. Conclusions: The combinational use of XMLI on conventional treatment may exert better therapeutic effects on improving cardiac function in CHF patients, indicating that XMLI was suggested to be considered during the conventional treatment of CHF. High-quality and large scale RCTs are still required to confirm the impacts of XMLI.

14.
Front Pharmacol ; 9: 624, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29946260

RESUMO

Objective: San-Cao granule (SCG), a traditional Chinese herb formula, has been used for treating autoimmune hepatitis (AIH) in our clinics for a long time. However, its active ingredients and mechanisms of action were still unknown due to its complicated chemical compositions. In the present study, the pharmacological study of SCG on acute liver injury induced by Concanavalin A (Con A) was performed to provide a scientific evidence for SCG against liver injury. Methods: In order to screen active components and predicate mechanisms of action, an "ingredients-target-disease" interaction network was constructed by network pharmacology. Then, the pharmacological study was performed to evaluate the therapeutic effect and the underlying mechanisms of SCG on Con A-induced liver injury in mice. Results: This research demonstrated the pharmacological effect of SCG on Con A-induced liver injury, which was through improving the liver function, relieving the pathological changes of liver tissue, decreasing the level of pro-inflammatory cytokines, and thus balancing the pro- and anti-inflammatory cytokines. And the anti-inflammatory of SCG may advantage over the ursodeoxycholic acid (UDCA). Network pharmacology analysis revealed that the pharmacological effect of SCG might be related to its active ingredients of taraxanthin, dihydrotanshinone I, isotanshinone I, γ-sitosterol, 3ß-acetyl-20,25-epoxydammarane-24α, and δ-7-stigmastenol. The hepatoprotective effect of SCG was reflected by suppressing Con A-induced apoptosis which was mediated by TRAIL and FASL. Conclusion: The combination of network pharmacology and experimental data has revealed the anti-apoptotic effect of SCG against Con A-induced liver injury.

15.
Artigo em Inglês | MEDLINE | ID: mdl-29849724

RESUMO

Background: Shexiang Baoxin pills (SXBXP), as a Traditional Chinese Medicine, are widely used for chronic heart failure in China. It is essential to systematically assess the efficacy and safety of SXBXP as an adjuvant treatment for chronic heart failure. Methods: Seven English and Chinese electronic databases (PubMed, Embase, Cochrane Library, CBM, Wanfang, VMIS, and CNKI) were searched from inception to July 2017. The Cochrane Risk of Bias tool was used to evaluate the methodological quality of eligible studies. Meta-analysis was performed by Review Manager 5.3. Results: A total of 27 RCTs with 2637 participants were included in this review. Compared to conventional treatment, SXBXP combined with conventional treatment showed potent efficacy when it came to the total efficacy rate (OR, 3.88; 95% CI, 2.87, 5.26; P < 0.00001), B-type natriuretic peptide (BNP) (MD = -66.95; 95% CI, -108.57, -25.34; P = 0.002), N-terminal pro-brain natriuretic peptide (NT-ProBNP) (MD = -0.15; 95% CI, -0.21, -0.09; P < 0.00001), six-minute walking distance (6-MWD) (MD = 38.57; 95% CI, 28.47, 48.67; P < 0.00001), cardiac output (CO) (MD = 0.84; 95% CI, 0.68, 0.99; P < 0.00001), and Stroke Volume (SV) (MD = 7.43; 95% CI, 4.42, 10.44, P < 0.00001). The pooled subgroup analysis indicated that there was a significant difference between SXBXP plus conventional treatment and conventional treatment alone in short term course (OR = 3.51; 95% CI, 2.28, 5.40; P < 0.00001), in middle period of treatment (OR = 5.01; 95% CI, 2.61, 9.60; P < 0.00001), and in long-term course (OR = 3.77; 95% CI, 2.13, 6.67; P < 0.00001). No serious adverse events or reactions were mentioned in these RCTs. Conclusions: As an adjuvant drug, this study suggested that SXBXP provide an obvious efficacy for the treatment of CHF. However, due to small samples and generally low quality studies being applied in this study, more rigorous and well-designed RCTs are needed to confirm these findings.

16.
Biomed Pharmacother ; 89: 61-68, 2017 May.
Artigo em Inglês | MEDLINE | ID: mdl-28214689

RESUMO

Paeoniflorin has shown the obvious effect on cholestasis according to our previous research. However, its mechanism has not been absolutely explored yet. This study aims at evaluating the potential effect of paeoniflorin on alpha-naphthylisothiocyanate (ANIT) -induced cholestasis by inhibiting nuclear factor kappa-B (NF-κB) and simultaneously regulating hepatocyte transporters. Cholestasis was induced by administration of ANIT. The effect of paeoniflorin on serum indices such as total bilirubin (TBIL), direct bilirubin (DBIL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (ALP), γ-glutamyltranspeptidase (γ-GT), total bile acid (TBA) and histopathology of liver were determined. Liver protein levels of NF-κB, interleukin 1ß (IL-1ß) and the hepatocyte transporters such as Na+/taurocholate cotransporting polypeptide (NTCP), bile salt export pump (BSEP), multidrug resistance-associated protein 2 (MRP2) and cholesterol 7α-hydroxylase (Cyp7a1) were investigated by western blotting. The results demonstrated that paeoniflorin could decrease serum ALT, AST, ALP, γ-GT, TBIL, DBIL and TBA in ANIT-treated rats. Histological examination revealed that rats treated with paeoniflorin represented fewer neutrophils infiltration, edema and necrosis in liver tissue compared with ANIT rats. Moreover, paeoniflorin significantly reduced the over expressions of NF-κB and IL-1ß induced by ANIT in liver tissue. In addition, the relative protein expressions of NTCP, BSEP, MRP2 but not Cyp7a1 were also restored by paeoniflorin. The potential mechanism of paeoniflorin in alleviating ANIT-induced cholestasis seems to be related to reduce the over expressions of NF-κB and hepatocyte transporters such as NTCP, BSEP as well as MRP2.


Assuntos
Proteínas de Transporte/metabolismo , Colestase/tratamento farmacológico , Glucosídeos/farmacologia , Inflamação/induzido quimicamente , Inflamação/prevenção & controle , Fígado/metabolismo , Monoterpenos/farmacologia , 1-Naftilisotiocianato , Animais , Bile/química , Bile/metabolismo , Biomarcadores/sangue , Colestase/sangue , Colestase/metabolismo , Edema/induzido quimicamente , Edema/prevenção & controle , Fígado/efeitos dos fármacos , Fígado/patologia , Testes de Função Hepática , Masculino , NF-kappa B/metabolismo , Necrose , Infiltração de Neutrófilos/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley
17.
Pharmacol Res ; 117: 357-369, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28087442

RESUMO

It has been suggested that excessive apoptosis in intervertebral disc cells induced by inflammatory cytokines, such as interleukin (IL)-1ß, is related to the process of intervertebral disc degeneration (IVDD). Hydrogen sulfide (H2S), a gaseous signaling molecule, has drawn attention for its anti-apoptosis role in various pathophysiological processes in degenerative diseases. To date, there has been no investigation of the correlation of H2S production and IVDD or of the effects of H2S on IL-1ß-induced apoptosis in nucleus pulposus (NP) cells. Here, we found that the expression levels of cystathionine ß-synthase (CBS) and cystathionine γ-lyase (CSE), two key enzymes in the generation of H2S, were significantly decreased in human degenerate NP tissues as well as in IL-1ß-treated NP cells. NaHS (H2S donor) administration showed a protective effect by inhibiting the endoplasmic reticulum (ER) stress response and mitochondrial dysfunction induced by IL-1ß stimulation in vitro, the effect was related to activation of the PI3K/Akt and ERK1/2 signaling pathways. Suppression of these pathways by specific inhibitors, LY294002 and PD98059, partially reduced the protective effect of NaHS. Moreover, in the percutaneous needle puncture disc degeneration rat tail model, disc degeneration was partially reversed by NaHS administration. Taken together, our results suggest that H2S plays a protective role in IVDD and the underlying mechanism involves PI3K/Akt and ERK1/2 signaling pathways-mediated suppression of ER stress and mitochondrial dysfunction in IL-1ß-induced NP cells.


Assuntos
Estresse do Retículo Endoplasmático/efeitos dos fármacos , Sulfeto de Hidrogênio/farmacologia , Degeneração do Disco Intervertebral/tratamento farmacológico , Mitocôndrias/efeitos dos fármacos , Doenças Mitocondriais/tratamento farmacológico , Núcleo Pulposo/efeitos dos fármacos , Substâncias Protetoras/farmacologia , Adolescente , Adulto , Idoso , Animais , Apoptose/efeitos dos fármacos , Células Cultivadas , Criança , Citocinas/metabolismo , Feminino , Humanos , Degeneração do Disco Intervertebral/metabolismo , Masculino , Pessoa de Meia-Idade , Mitocôndrias/metabolismo , Doenças Mitocondriais/metabolismo , Núcleo Pulposo/metabolismo , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Adulto Jovem
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