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Study on the effect and mechanism of Danzhi Qing’e Formula in improving lower urinary tract symptoms based on experiment and network pharmacology
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DOI   10.11656/j.issn.1673-9043.2023.03.10
Key Words   Danzhi Qing’e Formula;lower urinary tract symptom;detrusor;micturition parameter;network pharmacology
Author NameAffiliationE-mail
YANG Xiaohua Institute of Traditional Chinese Medicine of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
State Key Laboratory of Component Chinese Medicine of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Key Laboratory of Pharmacology of Traditional Chinese Medical Formula of Ministry of Education of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China 
 
LIU Erwei Institute of Traditional Chinese Medicine of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
State Key Laboratory of Component Chinese Medicine of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China 
 
MA Yaxuan Institute of Traditional Chinese Medicine of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Key Laboratory of Pharmacology of Traditional Chinese Medical Formula of Ministry of Education of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China 
 
WU Yaoxin Institute of Traditional Chinese Medicine of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
State Key Laboratory of Component Chinese Medicine of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China 
 
MIAO Lin Institute of Traditional Chinese Medicine of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
State Key Laboratory of Component Chinese Medicine of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China
Key Laboratory of Pharmacology of Traditional Chinese Medical Formula of Ministry of Education of Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China 
mmmlin@tjutcm.cn 
Abstract
    [Objective] To determine whether Danzhi Qing'e Formula(DZQE) has a potential role in regulating bladder function in the treatment of male lower urinary tract symptoms(LUTS),and to predict the possible mechanism involved. [Methods] The bladder perfusion was used to detect the effect of DZQE on urinary parameters in male rats. The rat detrusor strips were isolated and the relaxable and contractile effects of DZQE on basal and KCl-induced detrusor strips were detected. The active ingredients and their potential targets in DZQE were identified from traditional chinese medicine systems pharmacology database and analysis platform(TCMSP) and the encyclopedia of traditional chinese medicine(ETCM). The LUTS related disease targets were obtained from database GeneCards and DisGeNET. Then target overlaps between of active ingredients from DZQE and of disease were confirmed and the active components-targets network was conducted. The signaling pathway and biological function were subsequently analyzed by Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) through the database for annotation,visualization and integrated discovery(DAVID) v6.8. [Results] DZQE significantly reduced the detrusor leak point pressure(DLPP) and maximum voiding pressure(MVP) in male rats. Strip assays showed that DZQE directly promoted bladder detrusor contraction,but inhibited KCl-induced detrusor contraction. By network pharmacological screening,102 active components and 258 potential predictive targets of DZQE were obtained,and 246 targets of LUTS disease were set,which were further overlapped and 47 common targets with 59 active components of LUTS in the formula were finally confirmed. GO functional enrichment analysis showed that the main biological processes of DZQE on regulation of LUTS involved smooth muscle contraction,vasoconstriction,MAPK cascade,and estrogen response. KEGG enrichment result showed that DZQE regulated LUTS through 88 signaling pathways,including PI3K-Akt,thyroid hormone,calcium ion,estrogen,TNF,ErbB,MAPK,TGF-β signaling pathway. [Conclusion] DZQE regulated the symptoms of lower urinary tract in male rats through multiple signaling pathways.

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