[1] XU WeiyingSUN Yongning WANG Ziyang LIU MeizhiTU YanjieCAO YanZHE Zhe,.Clinical Study and Network Pharmacology MechanismExplorationof Huangqin Kechuan San in theTreatment of Bronchial Asthma [J]. Modern Traditional Chinese Medicine, 2024, (05): 51-61. [doi: 10.13424/j.cnki.mtcm.2024.05.011]
Clinical Study and Network Pharmacology MechanismExplorationof Huangqin Kechuan San in theTreatment of Bronchial Asthma
- Article number:
- 1672-0571(2024)04-0056-04
- Keywords:
- Key words:Huangqin Kechuan San; Bronchial asthma; Clinical efficacy; Network pharmacology targets; Molecular docking
- ZTFLH:
- R256.11
- Code:
- A
- Abstract:
- Abstract：Objective Based on network pharmacology，this study aims to investigate the effectiveness of Huangqin Kechuan San in preventing and treating bronchial asthma，as well as to explore its effective substances.Methods A total of 94 patients who met the inclusion criteria were randomly divided into a treatment group and a control group，with 47 patients in each group.All patients received routine medication treatment.The treatment group was given Huangqin Kechuan San Sanfu Paste，while the control group was given its analog Sanfu Paste.Compare the TCM symptom score，ACT score，frequency of disease attacks within six months，and serum eosinophil count (EOS) between two groups of patients before and after treatment.Exploring the possible effector substances and mechanisms of Huangqin Kechuan San in relation to bronchial asthma based on network pharmacology and molecular docking.Results The data showed that：① The total effective rate of clinical treatment in the treatment group was higher than that in the control group (P<0.05)；② The single symptom scores，ACT scores，and frequency of disease attacks within six months in the treatment group were lower than those in the control group (all P<0.05)，including cough，shortness of breath，wheezing，phlegm production，reduced appetite，loose stools，and fatigue.The EOS levels of both groups of patients decreased，and the values of various indicators in the treatment group were significantly lower than those in the control group (both P<0.05)；④Network pharmacology screening identified 26 potential targets of active ingredients in Huangqin Kechuan San that intersect with bronchial asthma.Key active ingredients include tetrahydroxyflavonoids，ethyl linoleate，palmitic acid，etc.Core targets include SIRT1，STAT3，ESR1，PPARA，etc.，which may involve biological processes such as immunity，fatty acid metabolism，hormone reactions，and cell necrosis factor reactions.⑤ Molecular docking showed that the effective active ingredient tetrahydroxyflavone (5，7，2′，6′-Tetrahydroxyflavone) in Huangqin Kechuan San was hydrogen bonded to the amino acids ILE411 and ILE411 of the key target SIRT1 in bronchial asthma GLU410、LYS408、SER370、LYS375.It binds to the amino acids ASP334 and LY2574 of STAT3，the amino acid LEU346 of ESR1，and the amino acids MET320，LEU331，and THR334 of PPARA.Conclusion Huangqin Kechuan San has reliable clinical efficacy in treating patients with bronchial asthma and lung spleen deficiency syndrome，and has a positive effect in improving clinical symptoms and reducing the frequency of disease attacks.According to network pharmacology analysis，Huangqin Kechuan San may exert therapeutic effects by targeting PI3K Akt，JAK-STAT，NF-κΒ，and other pathways through SIRT1，STAT3，ESR1，etc.，to alleviate airway inflammation and inhibit airway remodeling.Further molecular docking suggests that the active ingredient of the drug，tetrahydroxyflavone，has good binding ability with asthma disease targets SIRT1，STAT3，ESR1，and PPARA.
References:
［1］BATEMAN ED， HURD SS，BARNES PJ，et al.Global strategy for asthma management and prevention:GINA executive summary［J］.The European respiratory journal，31(1)，143-178.
［2］KURUVILLA ME，VANIJCHAROENKARN K，SHIH JA，et al.Epidemiology and risk factors for asthma［J］.Respiratory Medicine，2019，149:16-22.
［3］喻晓，石克华，折哲，等.咳喘散穴位敷贴治疗支气管哮喘慢性持续期临床疗效观察［J］.辽宁中医杂志，2012，39(5):876-878.
［4］中华医学会呼吸病学分会哮喘学组.支气管哮喘防治指南(2020年版)［J］.中华结核和呼吸杂志，2020，43(12):1023-1048.
［6］郑筱萸.中药新药临床研究指导原则:试行［M］.北京:中国医药科技出版社，2002:51-54.
［9］RU JL，LI P，WANG JN，et al.TCMSP:a database of systems pharmacology for drug discovery from herbal medicines［J］.Journal of Cheminformatics，2014，6:13.
［10］XU HY，ZHANG YQ，LIU ZM，et al.ETCM:an encyclopaedia of traditional Chinese medicine［J］.Nucleic Acids Research，2019，47(D1):D976-D982.
［11］BUSSE WW，KRAFT M，RABE KF，et al.Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation［J］.The European Respiratory Journal，2021，58(2):2003393.
［12］MANDLIK DS，MANDLIK SK.New perspectives in bronchial asthma:pathological，immunological alterations，biological targets，and pharmacotherapy［J］.Immunopharmacology and Immunotoxicology，2020，42(6):521-544.
［13］KURUVILLA ME，LEE FEH，LEE GB.Understanding asthma phenotypes，endotypes，and mechanisms of disease［J］.Clinical Reviews in Allergy & Immunology，2019，56(2):219-233.
［14］BERNSTEIN DI.ABCs of asthma［J］.Clinical Cornerstone，2008，8(4):9-25.
［15］PAVN-ROMERO GF，SERRANO-PREZ NH，GARCA-SNCHEZ L，et al.Neuroimmune pathophysiology in asthma［J］.Frontiers in Cell and Developmental Biology，2021，9:663535.
［16］KIM JS，KANG JY，HA JH，et al.Expression of nerve growth factor and matrix metallopeptidase-9/tissue inhibitor of metalloproteinase-1 in asthmatic patients［J］.The Journal of Asthma:Official Journal of the Association for the Care of Asthma，2013，50(7):712-717.
［17］NTONTSI P，PHOTIADES A，ZERVAS E，et al.Genetics and epigenetics in asthma［J］.International Journal of Molecular Sciences，2021，22(5):2412.
［18］RUSSELL RJ，BRIGHTLING C.Pathogenesis of asthma:implications for precision medicine［J］.Clinical Science，2017，131(14):1723-1735.
［19］BUSSE WW，KRAFT M，RABE KF，et al.Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation［J］.The European Respiratory Journal，2021，58(2):2003393.
［20］SAITO A，HORIE M，NAGASE T.TGF-β signaling in lung health and disease［J］.International Journal of Molecular Sciences，2018，19(8):2460.
［21］庞亚蓉，席建宏，王志旺，等.磷脂酰肌醇3激酶/蛋白激酶B(PI3K/Akt)信号通路参与哮喘气道炎症反应的研究现状［J］.中国临床药理学杂志，2021，37(14):1897-1901.
［22］LI H，WANG Z，ZHANG J，et al.Feifukang ameLiorates pulmonary fibrosis by inhibiting JAK-STAT signaling pathway［J］.BMC Complement Alten Med，2018，18(1):234.
［23］HU SHILING，WANG JUE，BAI HAOYUN，et al.Secreted phosphoprotein 1 regulates natural compound 3′，4′，5，7-tetrahydroxyflavone to inhibit mast cell-mediated allergic.inflammationJournal［J］.Immunopharmacology and immunotoxicology.Volume，Issue.2023，PP11-13.
［24］王蕊，刘军，杨大宇，等.白芷化学成分与药理作用研究进展［J］.中医药信息，2020，37(2):123-128.
［25］PARK SY，SEETHARAMAN R，KO MJ，et al.Ethyl linoleate from garlic attenuates lipopolysaccharide-induced pro-inflammatory cytokine production by inducing heme oxygenase-1 in RAW264.7 cells［J］.International Immunopharmacology，2014，19(2):253-261.
［26］YUAN J，LIU R，MA Y，et al.Curcumin attenuates airway inflammation and airway remolding by inhibiting NF-κB signaling and COX-2 in cigarette Smoke-induced COPD mice［J］.Inflammation，2018，41(5):1804-14.
［27］HU YANCHAO，FAN YAJIE，ZHANG CHUNYAN，et al.Palmitic acid inhibits vascular smooth muscle cell switch to synthetic phenotype via upregulation of miR-22 expression［J］.Aging,2022,14(19):8046-8060.
［28］陈桂英，刘国慧，姜雪，等.厚朴多糖通过调控调控PI3K/Akt信号通路对哮喘大鼠气道重塑的作用［J］.中成药，2024，46(4):1332-1336.
［29］毛蜀，何密斯，刘桂元，等.姜黄素对髓母细胞瘤PI3K/Akt信号通路的作用［J］.第三军医大学学报，2013，35(6):518-522.
［30］马春兰，张宝亮，刘晓明.雷公藤多苷抑制PI3K/AKT信号通路对肺腺癌细胞迁移和血管形成的影响［J］.安徽医药，2022，26(2):235-238.
［31］吴骞，丁榆德，程刚.山柰酚通过PI3K/Akt信号通路对口腔癌细胞增殖、侵袭及迁移的影响［J］.中药材，2020，43(12):3045-3049.
［32］雷俊.牛蒡子苷元抑制TLR4/TRAF6/NF-κB信号通路对哮喘模型大鼠气道重塑和Th1/Th2免疫平衡的影响［J］.免疫学杂志，2023，39(1):12-20.
［33］赖根祥，朱桂东，何慧明.栀子苷通过抑制TLR4/NF-κB信号通路减轻睡眠剥夺大鼠认知功能障碍［J］.中国病理生理杂志，2020，36(10):1810-1817.
［34］MA B，ATHARI SS，MEHRABI NASAB E.et al.PI3K/AKT/mTOR and TLR4/MyD88/NF-κB Signaling Inhibitors Attenuate Pathological Mechanisms of Allergic Asthma［J］.Inflammation，2021(44):1895-1907.
［35］吕川，朱慧志，刘向国，等.基于IL-6/JAK2/STAT3信号轴研究阳和平喘颗粒调控哮喘大鼠气道重塑作用机制［J］.海南医学院学报，2024，30(1):15-20，28.
［36］张文斌，王杰，王玮，等.健脾益肺汤抑制NF-κB/STAT3信号通路改善哮喘模型大鼠气道炎症及气道重塑作用研究［J］.中国中医急症，2019，28(5):806-808+832.
［37］付昆，杨艳，陆一菱，等.基于IL-6/STAT3和IL-2/STAT5信号通路探讨伏九贴敷药物调控Th17/Treg免疫平衡的抗哮喘作用机制［J］.中药新药与临床药理，2024，35(1):26-34.
［38］陈淑珍.中药单体治疗哮喘的作用与机制研究进展［J］.中医药学报，2021，49(10):89-93.［39］周旋，谭志团，任翼，等.柚皮素通过抑制NF-κB信号通路减轻哮喘大鼠气道炎症反应［J］.天津医药，2021，49(5):483-489.
Memo
基金项目：上海市卫生健康委员会科研课题（202040261）