The study on the mechanism of Tanreqing and ambroxol combined with Azithromycin for the treatment of mycoplasma pneumonia in children

Objective:To observe the mechanism of Tanreqing and ambroxol combined with Azithromy for the treatment of mycoplasma pneumonia in children and offer help to mycoplasma pneumonia treatment.Methods:86 cases of mycoplasma pneumonia patients in our hospital were selected and randomly divided into observation group and control group, each group were 43 cases. Control group was treated with conventional therapy, and observation group was treated with Tanreqing and ambroxol combined with Azithromy based on conventional therapy, the changes of lung function [V-T (Tidal volume)/kg, t-PTEF/t-E (time ratio of peak to peak), TEF25/PTEF (Instantaneous velocity of exhaling tidal volume 75% and Peak tidal expiratory flow ratio) and MTIF/MTEF (medium-term inspiratory flow rate and medium-term expiratory flow rate ratio)], cytokines (IL-2, IL-10, IL-6 and TNF-α) and the myocardial enzymes [LDH (lactate dehydrogenase), CK-MB (creatine kinase isoenzyme), CK (creatine kinase) and AST (glutamic-oxaloacetic transaminase)] were detected before and after treatment.Results: The comparison of lung function, cytokines and themyocardial enzymes in the two groups before treatment was not statistically significant (P>0.05). MTIF/MTEF, themyocardial enzymes (LDH, CK-MB, CK and AST) and cytokines (IL-10, IL-6 and TNF-α) in both groups after treatment significantly decreased compared with that before treatment (P<0.05);lung function (V-T/kg, t-PTEF/t-E, TEF25/PTEF), and IL-2 in both groups after treatment significantly increased compared with that before treatment (P<0.05). Lung function (V-T/kg, t-PTEF/t-E, TEF25/PTEF), and IL-2 in observation group after treatment increased more significantly than that in control group (P<0.05), and MTIF/MTEF, themyocardial enzymes (LDH, CK-MB, CK and AST) and cytokines (IL-10, IL-6 and TNF-α) decreased more significantly than that in control group (P<0.05).Conclusions:Tanreqing and ambroxol combined with Azithromy could improve lung function, cytokines and the myocardial enzymes in children with mycoplasma pneumonia, which has a very important clinical significance of the treatment to mycoplasma pneumonia.

Tanreqing injection auxiliary in the treatment of heart failure with pulmonary infection:A systematic review

Objective:To systematically evaluate the clinical efficacy and safety of Tanreqing injection in the treatment of heart failure complicated with pulmonary infection.Methods:The database of CNKI,SinoMed,VIP full text database,Wanfang database,Cochrance Library,Web of Science and PubMed were searched.The retrieval time was from the inception to August 2021.Clinical randomized controlled trial of Tanreqing injection in the treatment of heart failure complicated with pulmonary infection was collected,and two researchers independently screened the document data.Meta-analysis was performed using RevMan 5.4.1 software.Results:A total of 10 documents were included,including 862 cases of heart failure complicated with pulmonary infection,including 431 cases in the test group,and 431 cases in the control group.The Meta analysis showed that compared to the control group,the test group increased clinical efficiency[OR=4.56,95%CI(2.79,7.52),P<0.00001],reduced the value of C-reactive protein[MD=-7.55,95%CI(-11.40,-3.69),P=0.0001],reduced the time required to correct heart failure[OR=-4.04,95%CI(-4.59,-3.49),P<0.00001],reduced the number of days of the average hospitalization[MD=-4.78,95%CI(-6.67,-2.89),P<0.00001],and there were no statistically significant differences in the incidence of adverse reactions.Conclusion:Tanreqing injection,as an auxiliary treatment for heart failure complicated with pulmonary infection,has significantly effective effect on improving efficiency.Tanreqing injection has a certain advantage in reducing C-creative protein values,shortening the time of correcting heart failure,and reducing the number of days of the average hospitalization,and the adverse reactions are smaller.However,the overall quality of the included studies is low,and more high-quality randomized controlled trials are needed to increase the evidence-based basis.

Efficacy of Azithromycin sequential therapy combined with Tanreqing injection for treatment of children with mycoplasma pneumonia

Objective:To study the effect of Azithromycin sequential therapy combined with Tanreqing injection on serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α in children with mycoplasma pneumonia.Methods:A total of 80 children with mycoplasma pneumonia in our hospital from June 2014 to September 2016 were enrolled in this study. The subjects were divided into the control group (n=40) and the treatment group (n=40) randomly. The control group were treated with Azithromycin sequential therapy, the treatment group were treated with Azithromycin sequential therapy combined with Tanreqing injection. The two groups were treated for 2 periods. The serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α levels of the two groups before and after treatment were compared.Results: There were no significantly differences of the serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α levels of the two groups before treatment. The serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α levels of the two groups after treatment were significantly lower than before treatment, and that of the treatment group were significantly lower than the control group.Conclusion:Azithromycin sequential therapy combined with Tanreqing injection can significantly reduce the serum sTREM-1, CK, G-CSF, IL-10, CRP and TNF-α levels of children with mycoplasma pneumonia, have good clinical efficacy, and it was worthy clinical application.

Neuroprotective Effect and Mechanism of Tanreqing Injection on Ischemic Stroke:Insights from Network Pharmacology and in vivo Experiments

Objective To explore the neuroprotective effects and mechanism of Tanreqing Injection(TRQ)on treating ischemic stroke based on network pharmacology and in vivo experimental validation.Methods The chemical compounds of TRQ were retrieved based on published data,with targets retrieved from PubChem,Therapeutic Target Database and DrugBank.Network visualization and analysis were performed using Cytoscape,with protein-protein interaction networks derived from the STRING database.Enrichment analysis was performed using Kyoto Encyclopedia of Genes Genomes pathway and Gene Ontology analysis.In in vivo experiments,the middle cerebral artery occlusion(MCAO)model was used.Infarct volume was determined by 2,3,5-triphenyltetrazolium hydrochloride staining and protein expressions were analyzed by Western blot.Molecular docking was performed to predict ligand-receptor interactions.Results We screened 81 chemical compounds in TRQ and retrieved their therapeutic targets.Of the targets,116 were therapeutic targets for stroke.The enrichment analysis showed that the apelin signaling pathway was a key pathway for ischemic stroke.Furthermore,in in vivo experiment we found that administering with intraperitoneal injection of 2.5 mL/kg TRQ every 6 h could significantly reduce the infarct volume of MCAO rats(P<0.05).In addition,protein levels of the apelin receptor(APJ)/phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)pathway were increased by TRQ(P<0.05).In addition,41 chemical compounds in TRQ could bind to APJ.Conclusions The neuroprotective effect of TRQ may be related to the APJ/PI3K/AKT signaling pathway.However,further studies are needed to confirm the findings.

Effects of Tanreqing Injection on ICU Mortality among ICU Patients Receiving Mechanical Ventilation: Time-Dependent Cox Regression Analysis of A Large Registry

Objective To assess whether the use of Tanreqing(TRQ)Injection could show improvements in time to extubation,intensive care unit(ICU)mortality,ventilator-associated events(VAEs)and infection-related ventilator associated complication(IVAC)among patients receiving mechanical ventilation(MV).Methods A time-dependent cox-regression analysis was conducted using data from a well-established registry of healthcare-associated infections at ICUs in China.Patients receiving continuous MV for 3 days or more were included.A time-varying exposure definition was used for TRQ Injection,which were recorded on daily basis.The outcomes included time to extubation,ICU mortality,VAEs and IVAC.Time-dependent Cox models were used to compare the clinical outcomes between TRQ Injection and non-use,after controlling for the influence of comorbidities/conditions and other medications with both fixed and time-varying covariates.For the analyses of time to extubation and ICU mortality,Fine-Gray competing risk models were also used to measure competing risks and outcomes of interest.Results Overall,7,685 patients were included for the analyses of MV duration,and 7,273 patients for the analysis of ICU mortality.Compared to non-use,patients with TRQ Injection had a lower risk of ICU mortality(Hazards ratios(HR)0.761,95%CI,0.581–0.997),and was associated with a higher hazard for time to extubation(HR 1.105,95%CI,1.005–1.216),suggesting a beneficial effect on shortened time to extubation.No significant differences were observed between TRQ Injection and non-use regarding VAEs(HR 1.057,95%CI,0.912–1.225)and IVAC(HR 1.177,95%CI,0.929–1.491).The effect estimates were robust when using alternative statistic models,applying alternative inclusion and exclusion criteria,and handling missing data by alternative approaches.Conclusion Our findings suggested that the use of TRQ Injection might lower mortality and improve time to extubation among patients receiving MV,even after controlling for the factor that the use of TRQ changed over time.

Effect of Tanreqing Injection(痰热清注射液)on Treatment of Acute Exacerbation of Chronic Obstructive Pulmonary Disease with Chinese Medicine Syndrome of Retention of Phlegm and Heat in Fei(肺)

Objective：To explore the effect of Tanreqing Injection（痰热清注射液,TRQI） on the treatment of acute exacerbation of chronic obstructive pulmonary disease（AECOPD） with Chinese medicine syndrome of retention of phlegm and heat in Fei（痰热阻肺证,RPHF）.Methods：In a prospective randomized controlled clinical trial,90 patients with AECOPD of RPHF syndrome were randomly assigned to 3 groups,TRQI and controls A and B,each with 30 cases.The TRQI group was administered with the intravenous injections of 20 mL TRQI once a day and conventional Western medicine treatment.Control group A was administered with the intravenous injection of 15 mg ambroxol hydrochloride twice a day and conventional Western medicine treatment,and control group B was administered with conventional Western medicine treatment only.The treatments were administered for 10 days.Chinese medical symptoms and signs were scored,and plasma concentrations of interleukin（IL）-8 and neutrophil elastase（NE） were recorded.Results：（1） The Chinese medical symptoms （cough,sputum amount,expectoration,dyspnea and fever） and signs（tongue and pulse） improved significantly in the TRQI group（P〈0.05 or P〈0.01）,and improvements in cough,sputum amount and expectoration were better in the TRQI group than control group B（P〈0.05）;there was no significant difference between the TRQI group and control group A（P〉0.05）.The sign of tongue was also improved significantly in the TRQI group （P〈0.05）.（2） The overall effects in the TRQI group and control group A were significantly better than in control group B（P〈0.05）,with no significant differences between the TRQI group and control group A（P〉0.05）.There was no significant difference in the total effective rate among the three groups（P〉0.05）.（3） After treatment, the plasma concentrations of IL-8 and NE decreased in the TRQI group and control group A（P〈0.05）,and the concentration of IL-8 in control group B decreased（P〈0.05）.The difference in IL-8 was greater in the TRQI group than in control group A and B before and after treatment,and the change in NE was greater in control group A than in the TRQI group and control group B,but there was no statistical significance among the three groups with regards to the change in IL-8 or NE（P〉0.05）.Conclusion：TRQI could improved the Chinese medical signs and symptoms in the patients with AECOPD,possibly because of the decreasing plasma levels of IL-8 and NE which could improve response to airway inflammation and mucus hypersecretion.

Screening and identification of multiple components in Tanreqing injection using RP-HPLC combined with DAD and ESI-TOF/MS

A liquid chromatography coupled with diode array detector(DAD) and electrospray ionization time-of-flight mass spectrometry(ESI-TOF/MS) method was developed for the screening and identification of the multiple components in Tanreqing injection, a well-known Chinese medicine injection in China. By combining the DAD spectrum and the accurate mass measurement of ESI-TOF/MS, twelve components in Tanreqing injection were identified. This study contributes to clarifying the nature of Tanreqing injection, and provides an effective and reliable process for the comprehensive and systematic characterization of complex traditional Chinese medicine preparations.

LC-MS/MS analysis and pharmacokinetic study on five bioactive constituents of Tanreqing injection in rats

Tanreqing injection(TRQ), a well-known traditional Chinese medicine formula, is commonly used to treat respiratory diseases. In the present study, a rapid, selective, and sensitive liquid chromatography-tandem mass spectrometry(LC-MS/MS) method was developed and validated to simultaneously determinate the plasma contents of 5 major constituents of TRQ, including chlorogenic acid(CHA), caffeic acid(CFA), baicalin(BA), ursodeoxycholic acid(UDCA) and chenodeoxycholic acid(CDCA) in rats after intravenous administration of TRQ. Chromatographic separation was performed on an Agilent Zorbax SB-C_(18) column(3.5 μm, 100 mm × 2.1 mm), with acetonitrile and 0.1% aqueous formic acid as mobile phase at a flow rate of 0.3 m L·min^(^(-1)). The calibration curves were linear over the ranges of 27.0–13 333.0 ng·m L^(-1) for CFA, 30.0–14 933.0 ng·m L^(-1) for CHA, 50.0–50 333.0 ng·m L^(-1) for BA, 550.0–55 000.0 ng·m L^(-1) for UDCA, and 480.0–48 000.0 ng·m L^(-1) for CDCA, respectively. Intra- and inter-day precisions(relative standard deviations, RSDs) were from 3.11% to 14.08%. The extraction recoveries were greater than 71% and accuracy(relative recovery) was from 89% to 137% for all analytes, except endogenous bile acids. This validated method was successfully applied to the first pharmacokinetic study of CFA, CHA, BA, UDCA and CDCA in rat plasma after intravenous administration of TRQ.

Effects of Tanreqing Capsule on the negative conversion time of nucleic acid in patients with COVID-19:A retrospective cohort study

Objective:Traditional Chinese medicine plays a significant role in the treatment of the pandemic of coronavirus disease 2019(COVID-19).Tanreqing Capsule(TRQC)was used in the treatment of COVID-19 patients in the Shanghai Public Health Clinical Center.This study aimed to investigate the clinical efficacy of TRQC in the treatment of COVID-19.Methods:A retrospective cohort study was conducted on 82 patients who had laboratory-confirmed mild and moderate COVID-19;patients were treated with TRQC in one designated hospital.The treatment and control groups consisted of 25 and 57 cases,respectively.The treatment group was given TRQC orally three times a day,three pills each time,in addition to conventional Western medicine treatments which were also administered to the control group.The clinical efficacy indicators,such as the negative conversion time of pharyngeal swab nucleic acid,the negative conversion time of fecal nucleic acid,the duration of negative conversion of pharyngeal-fecal nucleic acid,and the improvement in the level of immune indicators such as T-cell subsets(CD3,CD4 and CD45)were monitored.Results:COVID-19 patients in the treatment group,compared to the control group,had a shorter negative conversion time of fecal nucleic acid(4 vs.9 days,P=0.047)and a shorter interval of negative conversion of pharyngeal-fecal nucleic acid(0 vs.2 days,P=0.042).The level of CD3+T cells increased in the treatment group compared to the control group([317.09±274.39]vs.[175.02±239.95]counts/l L,P=0.030).No statistically significant differences were detected in the median improvement in levels of CD4+T cells(173 vs.107 counts/l L,P=0.208)and CD45+T cells(366 vs.141 counts/l L,P=0.117)between the treatment and control groups.Conclusion:Significant reductions in the negative conversion time of fecal nucleic acid and the duration of negative conversion of pharyngeal-fecal nucleic acid were identified in the treatment group as compared to the control group,illustrating the potential therapeutic benefits of using TRQC as a complement to conventional medicine in patients with mild and moderate COVID-19.The underlying mechanism may be related to the improved levels of the immune indicator CD3+T cells.

Intervention effect and dose-dependent response of Tanreqing injection on airway inflammation in lipopolysaccharide-induced rats

OBJECTIVE: To assess the effect of Tanreqing injection on airway inflammation in rats. METHODS: A rat model of airway inflammation was generated with lipopolysaccharide (LPS). Tanreqing injection was given by intratracheal instillation, and bronchoalveolar lavage fluid (BALF) from the right lung was collected. BALF total cell and neutrophil counts were then determined. In addition, BALF levels of inflammatory cytokines interleukin-1β, cytokine-induced neutrophil chemoattractant-1, and tumor necrosis factor-α were measured using enzyme linked immunosorbent assay.The middle lobe of the right lung was stained with hematoxylin-eosin and histological changes examined. RESULTS: LPS increased airway inflammation, decreased BALF inflammatory cell count, inflammatory cytokine levels, and suppressed leukocyte influx of the lung. The LPS-induced airway inflammation peaked at 24 h, decreased beginning at 48 h, and had decreased markedly by 96 h. CONCLUSION: Tanreqing injection contains anti-inflammatory properties, and inhibits airway inflammation in a dose-dependent manner.

Protective effect of Tanreqing injection on axon myelin damage in the brain of mouse model for experimental autoimmune encephalomyelitis

OBJECTIVE: To evaluate the effect of Tanreqing injection on axon myelin in the mouse brain of experimental autoimmune encephalomyelitis(EAE).METHODS: An EAE model was established by myelin oligodendrocyte glycoprotein(MOG)35-55 immunization in C57BL/6 mice. Mice were randomly divided into the following groups: normal, model,prednisone acetate(PA)(6 mg/kg), Tanreqing high dose(5.14 m L/kg), Tanreqing low dose(2.57 m L/kg). On the day of immunization, both Tanreqing groups were treated by intraperitoneal injection,with the PA group treated by intragastrical perfusion after T cell response, and the other groups treated with saline. Changes in body weight, neurological deficit score, incidence rate, mortality rate,and course of disease were observed for all mice.Brain tissue was isolated and stained with hematoxylin-eosin, and pathological investigations performed to evaluate axon myelin damage by transmission electron microscopy(TEM). Myelin basic protein and microtubule associated protein-2 were analyzed by immunohistochemistry.RESULTS: Tanreqing injection significantly prolonged EAE latency and decreased the neurological deficit score, alleviated infiltration of inflammatory cells in the focus area, up-regulated hippocampal MBP expression at the acute stage and the remission stage, and increased microtubule associated protein-2 expression in the EAE brain to varying degrees in the acute stage. TEM analysis indicated that Tanreqing injection alleviates myelin damage in the EAE mouse and maintains the integrity of circular layer structures and alleviates axon mitochondrial swelling.CONCLUSION: Tanreqing injection alleviates EAE symptoms.

Metabolic profiling of endogenous bile acids:a novel method to assess hepatoprotective effect of Tanreqing capsule on carbon-tetrachloride-induced liver injury in rats

Tanreqing(TRQ), a traditional Chinese medicine(TCM) formula, can alleviate liver injury and improve liver function. Its pharmacological mechanisms of actions are still unclear due to its complex components and multi-target natures. Metabolomic study is an effective approach to investigating drug pharmacological actions, new diagnostic markers, and potential mechanisms of actions. In the present study, a new strategy was used to evaluate the protective effect of TRQ capsule against carbon tetrachloride(CCl_4)-induced hepatotoxicity in rats, by analyzing metabolic profiling of endogenous bile acids(BAs) along with biochemical and histological analyses. BAs concentrations were determined by ultra-performance liquid chromatography coupled with quadrupole mass spectrometry(UPLC-MS). Principal component analysis and partial least squares discriminant analysis were then employed to analyze the UPLC-MS results and compare the hepatoprotective effect of TRQ capsule in different groups at the doses of 0.36, 1.44, and 2.88 g·kg^(-1) body weight, respectively. Moreover, our results suggested that taurocholic acid(TCA) and taurohyodesoxycholic acid(THDCA) were the most important biochemical markers, which were indicative of CCl_4-induced acute hepatic damage and hepatoprotective effect of TRQ capsule. Therefore, this new strategy would be an excellent alternative method for evaluating hepatoprotective effect and proposing potential mechanisms of action for other drugs as well.

Tanreqing Injection(痰热清注射液) for Patients with Influenza: A Systematic Review and Meta-analysis of Randomized Controlled Trials

Objective:To systematically evaluate the efficacy and safety of Tanreqing Injection(痰热清注射液,TRQI)combined with conventional treatment on clinical outcomes in the treatment of patients with influenza.Methods:The electronic databases searched were Cochrane Central Register of Controlled Trials(CENTRAL,The Cochrane Library),MEDLINE(PubMed),EMbase(OvidSP),Chinese Bio-medical Literature and Retrieval System(Sinomed),China National Knowledge Infrastructure Database(CNKI),China Science and Technology Journal Database(VIP)and WanFang Data Knowledge Service Platform,and we checked the reference sections of the retrieved articles as well.The search was performed in October 2018,and we used the randomized controlled trials(RCTs)that corresponded to the new diagnostic criteria for influenza.Two review authors independently screened the internalized articles in accordance with the Preferred Reporting Items for Systematic review and Meta-Analysis(PRISMA)statement checklist.We evaluated the quality of the articles and extracted the data from the studies using the Revmen5.3 software.Results:We included 12 RCTs of over 882 cases in this meta-analysis.Compared to conventional treatment,TRQI combined with conventional treatment could increase the total effective rate[9 RCTs,n=648,odds ratio(OR):4.92,95%confidence interval(CI):2.94,8.24,P<0.0001,random effects model],decrease the average time for fever clearance[7 RCTs,n=564,mean difference(MD):–1.08,95%CI:–1.68,–0.48,P=0.0004,random effects model]and decrease the time for resolution of cough(5 RCTs,n=362,MD:–1.76,95%CI:–2.63,–0.90,P<0.0001,random effects model).Conclusion:Based on this meta-analysis of RCTs,TRQI combined with conventional treatment had a statistically significant benefit in increasing the total effective treatment rate and reducing the time for fever clearance as well as time for resolution of cough.