| Objective:Jinshui Liujun decoction is a classic prescription commonly used in clinical practice.The prescription and application characteristics of Jinshui Liujun decoction were discussed on the basis of reviewing the ancient and modern literatures.The network pharmacology method was used to construct the component-target-pathway network of Jinshui Liujun decoction in the treatment of chronic obstructive pulmonary disease(COPD),to predict the characteristics of its effect mechanism.The therapeutic effect and antioxidant mechanism of the Jinshui Liujun decoction were observed on COPD rats model induced by smoke combined with lipopolysaccharide(LPS).The above work provides support for the application of Jinshui Liujun decoction on clinicMethods:1.Relevant expositions of Jinshui Liujun decoction were collected and sorted out in literatures of traditional Chinese medicine.Relevant literatures of Jinshui Liujun decoction were searched in CNKI database,Wanfang database and Weipu database from the time of establishment to the year of 2019.The modern clinical disease spectrum of Jinshui Liujun decoction was established to summarize the compatibility and application characteristics of Jinshui Liujun decoction.2.The network pharmacology method was used to construct the component-target-pathway network,and the potential targets of Jinshui liujun decoction and its components in treating COPD were analyzed.The compunds and targets information of Jinshui Liujun decoction and its components mainly came from TCMSP database,while the targets information of COPD mainly came from TTD,CTD,GeneCards and DisGNET database.GO and KEGG enrichment analysis were carried out by Omishare open platform.Cytoscape software was used to draw the network map3.The COPD rats model induced by smoke combined with LPS was duplicated.To observe the weight of rats,Lee’s index,thymus index,spleen index,number of inflammatory cells in bronchoalveolar lavage fluid(BALF),changes of lung function and lung histopathology damage To detect the contents of reactive oxygen species(ROS),malondialdehyde(MDA)and superoxide dismutase(SOD)in lung tissues,as well as the protein expressions of peroxisome proliferator activated receptor gamma(PPAR-y),heme oxygenase 1(HO-1)in lung tissues.The above work was to explore the anti-oxidation mechanism of Jinshui Liujun decoction in the treatment of COPDResults:1.According to the original record in Jing Yue Quan Shu,Jinshui Liujun decoction was used to treat cough,shortness of breath and vomiting.Doctors in later generations extended the application of this prescription on the basis of the original use.Its pathogenesis included the deficiency of lung and kidney,and the interior filling of wet and phlegm.In modern clinical application,Jinshui Liujun decoction is mainly used for pulmonary diseases due to the deficiency of lung and kidney,including COPD,chronic bronchitis,cough and asthma.2.Network pharmacology analysis showed that in Jinshui Liujun decoction,435 functional compounds mainly acted on 96 targets and 17 signaling pathways.Among them,top 20 compounds with high frequency included quercetin,acetic acid,stigmasterol,kaempferol,sitogluside,palmitic acid,beta-sitosterol,linoleic acid,naringenin,oleic acid,ursolic acid,etc.,and the targets with higher degree values were MAPK3,TNF,PPAR-γ,LPL,HO-1,MAPK8,NR3C1,MPO,CAT,SIRT1,MAPK1,STAT3,GAPDH,GCG,CRP,AHR,α1-AT,INS,VEGFA,EGFR The mechanism of Jinshui Liujun decoction in treating COPD was mainly through Anti-inflammation,antioxidant,inhibition of protease/antiprotease imbalance,improvement of airway remodeling and airway mucus hypersecretion.3.The network analysis of the components of Jinshui Liujun decoction showed that prescription 1(prepared radix rehmanniae,angelica)acted on 27 targets and prescription 2(pinellia,tangerine peel,poria,prepared licorice,ginger)acted on 71 targets.Besides,there were 2 unique targets of prescription 1,69 unique targets of prescription 2,and 25 common targets from prescription 1 and prescription 2.The first one mainly worked on metabolic and neuroregulatory signaling pathways,while the second one was mainly involved in the pathways of inflammation and immunity,oxidative stress and airway remodeling4.Compared with the control group,the model group rats had lower weight growth(P<0.01),lower minute volume(MV),peak inspiratory flow(PIF)and peak expiration flow(PEF)(p<0.01),higher inflammatory cells numbers in BALF(p<0.01),as well as lower Lee’s index,thymus index and spleen index(p<0.01).Besides,in model group,lung tissue histopathology largely damaged,levels of ROS,MDA significantly increased(p<0.01),SOD level decreased(p<0.01),and protein expressions of PPAR-y and HO-1 reduced(p<0.01).Compared with the model group,the body weight in the high,medium and low dose groups of Jinshui Liujun decoction was increased(P<0.01).MV in the high and medium dose groups increased(P<0.01),and MV in the low dose group increased as well(P<0.05).PIF was increased in high,medium and low dose groups,as well as in the positive group(P<0.01).PEF was increased in high and medium dose groups(P<0.05).The number of inflammation cells in BALF decreased in the high,medium and the positive group(P<0.01),as well as in the low dose group(P<0.05).The Lee’s index increased in the medium dose group(P<0.05).Thymus index increased in high,medium dose groups(P<0.05).The splenic index increased in the high and medium dose groups(P<0.01),as well as in the low dose group(P<0.05).Lung histopathological injury was improved;The ROS content decreased in the high and medium dose groups(P<0.01),as well as in the low dose group and the positive group(P<0.05).MDA content decreased in the medium dose group and the positive group(P<0.01),as well as in the high dose group(P<0.05).SOD content increased in the high dose group(P<0.01),as well as in the middle dose group(P<0.01).The protein expressions of PPAR-yincreased in the high dose group(P<0.01),and in the middle dose group and the positive group(P<0.05).HO-1 protein expressions increased in the medium dose group(P<0.05).Conclusions:1.Jinshui Liujun decoction was mainly used for cough,asthma and other diseases in middle Jiao due to the deficiency in lung and kidney with phlegm and dampness.In modern clinical application,Jinshui Liujun decoction is mainly used for the syndromes of deficiency in lung and kidney,such as COPD,chronic bronchitis,cough and asthma,etc.e,in which COPD has the highest support degree,which is 35%2.The research on the component-target-pathway network of Jinshui Liujun decoction found that it was mainly used to treat COPD through anti-inflammatory,antioxidant,inhibiting the imbalance of protease/anti-protease,improving airway remodeling and airway mucus hypersecretion,with multiple components,multiple targets and multiple pathways.3.The network analysis of the components of Jinshui Liujun decoction showed that the prescription 1 was mainly involved in metabolic and neuroregulatory signaling pathways,and the prescription 2 mainly worked on the inflammation and immunity,oxidative stress and airway remodeling pathways,with different emphases and synergistic effects.4.The experimental results showed that the effects of Jinshui Liujun decoction included improving the nutritive status of COPD rats,improving weight,Lee’s index,thymus index,spleen index,reducing inflammatory cells infiltration,improving lung function,reducing the lung tissue histopathological damage.The mechanism was associated with the decrease of the contents of ROS and MDA,the increase of SOD content,as well as the regulation of PPAR-y and HO-1 proteins to reduce oxidation damage in treating COPD.The above results provide basic data for the experimental and clinical research of Jinshui Liujun decoction. |
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