RESUMO
This study aimed to systematically evaluate the effectiveness and safety of Tanreqing Injection in the treatment of severe pneumonia in the elderly. Eighteen randomized controlled trials(RCTs) involving 1 457 elderly patients with severe pneumonia were included in the study after conducting searches in both Chinese and English databases as well as clinical trial registration platforms. The quality of the included studies was assessed using the Cochrane risk of bias assessment tool. Meta-analysis were conducted using RevMan 5.4 and Stata 17 software, and trial sequential analysis(TSA) was performed using TSA 0.9.5.10 beta software. Meta-analysis results showed that compared with conventional western medicine treatment, Tanreqing Injection + conventional western medical significantly improved the clinical effectiveness in elderly patients with severe pneumonia(RR=1.26, 95%CI[1.20, 1.32], P<0.000 01), arterial oxygen partial pressure(SMD=6.23, 95%CI[3.29, 9.18], P<0.000 1), oxygenation index(SMD=11.72, 95%CI[4.41, 19.04], P=0.002), reduce procalcitonin(SMD=-6.16, 95%CI[-8.10,-4.21], P<0.000 01), C-reactive protein(SMD=-8.50, 95%CI[-11.05,-5.96], P<0.000 01), white blood cell count(SMD=-4.56, 95%CI[-5.73,-3.39], P<0.000 01), and shortened the duration of fever(SMD=-3.12, 95%CI[-4.61,-1.63], P<0.000 1), cough(SMD=-4.84, 95%CI[-6.90,-2.79], P<0.000 01), lung rales(SMD=-0.99, 95%CI[-1.54,-0.44], P=0.000 4), and mechanical ventilation time(SMD=-3.26, 95%CI[-5.03,-1.50], P=0.000 3), increase CD4~+ T-cell levels(SMD=6.73, 95%CI[5.23, 8.23], P<0.000 01) and CD8~+ T-cell levels(SMD=7.47, 95% CI[5.32, 9.61], P<0.000 01) with no significant adverse reactions. TSA confirmed the stability and reliability of the results related to clinical effectiveness. This study suggests that Tanreqing Injection, as a Chinese medicinal preparation, has a significant therapeutic effect and good safety profile in the treatment of severe pneumonia in elderly patients. Due to the limited quality of the included studies, high-quality RCT is still needed to provide evidence support for the above conclusions.
Assuntos
Medicamentos de Ervas Chinesas , Pneumonia , Idoso , Humanos , Tosse/induzido quimicamente , Medicamentos de Ervas Chinesas/efeitos adversos , Pneumonia/tratamento farmacológico , Reprodutibilidade dos Testes , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Luteolin, a natural flavonoid exists in various medicinal plants, has strong anti-inflammatory effect. However, anti-inflammatory mechanism of luteolin has not been fully explored. Hence, we systematically investigated druggability and anti-inflammatory mechanism of luteolin based on network pharmacology and in vitro experiments. The absorption, distribution, metabolism and excretion of luteolin were evaluated by TCMSP server. Targets associated with luteolin and inflammation were collected from public databases, and the overlapping targets between luteolin and inflammation were analyzed by Draw Venn diagram. Then the protein-protein interaction network of luteolin against inflammation was constructed. Further, gene function and pathway enrichment analysis were performed. Finally, in vitro experiments were carried out to estimate the accuracy of predicted target genes. ADME results indicated that luteolin has great potential to be developed into a drug. 226 overlapping targets were screened by matching 280 targets of luteolin with 9015 targets of inflammation. 9 core targets of luteolin against inflammation were identified, including MMP9, MAPK1, HSP90AA1, CASP3, ALB, EGFR, SRC, HRAS and ESR1. Gene function were mainly involved in metabolism, energy pathways and signal transduction. Metabolic pathways, pathways in cancer, PI3K-AKT signaling pathway, Ras signaling pathway and so on might be the critical pathways of luteolin against inflammation. RT-qPCR and ELISA results indicated that luteolin decreased the expression of most of core genes at protein and mRNA levels (MMP9, MAPK1, HSP90AA1, EGFR, SRC and HRAS). Luteolin is expounded to have great potential to be developed into a drug and target various genes and pathways to perform anti-inflammatory effect.
Assuntos
Anti-Inflamatórios/farmacologia , Luteolina/farmacologia , Proteoma/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos , Animais , Anti-Inflamatórios/farmacocinética , Anti-Inflamatórios/uso terapêutico , Caspase 3/metabolismo , Biologia Computacional , Bases de Dados Genéticas , Bases de Dados de Produtos Farmacêuticos , Receptores ErbB/metabolismo , Receptor alfa de Estrogênio/metabolismo , Proteínas de Choque Térmico HSP90/metabolismo , Inflamação/tratamento farmacológico , Inflamação/genética , Luteolina/farmacocinética , Luteolina/uso terapêutico , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Mapas de Interação de Proteínas , Proteínas Proto-Oncogênicas p21(ras)/metabolismo , Proteínas Proto-Oncogênicas pp60(c-src)/metabolismo , Células RAW 264.7 , Albumina Sérica/metabolismo , Transdução de Sinais/efeitos dos fármacosRESUMO
The randomized controlled trials( RCTs) about modified Sanzi Yangqin Decoction in the treatment of patients with exacerbation of chronic obstructive pulmonary disease( AECOPD) were collected from 7 databases( PubMed,CNKI,etc.) till December25,2018 from their inception. All the studies searched were strictly evaluated and independently screened by two researchers according to the inclusion and exclusion criteria,and the methodological quality of included studies was evaluated. In order to systematically review the efficacy and safety of modified Sanzi Yangqin Decoction for treating AECOPD,the Meta-analysis and trial sequential analysis were conducted by using Stata/SE 14. 0 and TSA 0. 9. 5. 10 Beta,respectively. A total of 22 RCTs involving 2 012 patients were included. The results of Meta-analysis suggested that: as compared with the control group,the clinical symptoms in AECOPD patients were improved( RR = 1. 19,95%CI[1. 15,1. 24],P = 0); the pulmonary functions including forced expiratory volume in one second( FEV_1)( SMD= 0. 96,95%CI[0. 39,1. 52],P= 0. 001),the percentage of forced expiratory volume in one second( FEV_1%)( SMD =0. 80,95%CI[0. 20,1. 41],P = 0. 009),forced vital capacity( FVC)( SMD = 0. 69,95% CI[0. 06,1. 31],P = 0. 032),first seconds breathing volume percentage of forced vital capacity( FEV_1/FVC) were improved( SMD = 0. 81,95%CI[0. 64,0. 97],P = 0);the arterial oxygen partial pressure( PaO_2) was improved( SMD= 0. 87,95%CI[0. 41,1. 32],P= 0); the arterial partial pressure of carbon dioxide( PaCO_2) was decreased( SMD =-0. 91,95%CI[-1. 33,-0. 49],P = 0) in the trial group. In addition,the incidence of adverse reactions in the experimental group was low,and there were no serious adverse events. The trial sequential analysis( TSA) showed that the studies included in the improvement of clinical efficacy had passed the conventional and TSA threshold at the same time,further confirming the efficacy of trial group. This research showed that,conventional Western medicine treatment,combined with modified Sanzi Yangqin Decoction in treating acute exacerbation patients with chronic obstructive pulmonary disease could improve the clinical efficiency and pulmonary functions,improve the PaO_2,decrease the PaCO_2,with a high safety. However,the quality of existing research is low,requiring more high quality clinical trials for further validation.