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北京中医药大学 中医学院,北京 102488
胡珂,在读硕士,从事中医药在生殖内分泌的作用和机制研究,E-mail:1344097332@qq.com
郭健,教授,博士生导师,从事中医药在生殖内分泌的作用和机制研究,E-mail:guojian323@sina.com
纸质出版日期:2022-06-20,
网络出版日期:2022-03-08,
收稿日期:2021-11-23,
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胡珂,许亚辉,刘殿龙等.基于网络药理学的五子衍宗丸抗睾丸炎症作用机制[J].中国实验方剂学杂志,2022,28(12):218-224.
HU Ke,XU Ya-hui,LIU Dian-long,et al.Anti-testicular Inflammation Mechanism of Wuzi Yanzongwan Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(12):218-224.
胡珂,许亚辉,刘殿龙等.基于网络药理学的五子衍宗丸抗睾丸炎症作用机制[J].中国实验方剂学杂志,2022,28(12):218-224. DOI: 10.13422/j.cnki.syfjx.20220613.
HU Ke,XU Ya-hui,LIU Dian-long,et al.Anti-testicular Inflammation Mechanism of Wuzi Yanzongwan Based on Network Pharmacology[J].Chinese Journal of Experimental Traditional Medical Formulae,2022,28(12):218-224. DOI: 10.13422/j.cnki.syfjx.20220613.
目的
2
通过网络药理学分析和实验验证,探讨五子衍宗丸抑制睾丸炎症可能的作用机制。
方法
2
通过中药系统药理学数据库与分析平台(TCMSP)检索五子衍宗丸的活性成分,利用SwissTargetPredicition平台进行有效成分靶点预测,GeneCards数据库和在线人类孟德尔遗传数据库(OMIM)获得已知治疗睾丸炎症的相关靶点,STRING 11.0数据库进行蛋白质-蛋白质相互作用(PPI)网络分析,利用Cytoscape 3.7.1软件构建“五子衍宗丸药物组成-有效成分-靶点”和“五子衍宗丸有效成分-疾病靶点”网络图,Metascape平台进行基因本体(GO)分析及京都基因与基因组百科全书(KEGG)信号通路富集分析。
结果
2
筛选出五子衍宗丸72个有效成分,624个潜在靶点,共发现五子衍宗丸抗睾丸炎症有196个可能的重要靶点。GO富集分析结果表明,五子衍宗丸抗睾丸炎症的潜在靶点涉及对细菌起源分子的反应、对外界刺激反应的正向调节及对细胞外刺激的反应等生物学过程。KEGG富集分析得到与五子衍宗丸抗睾丸炎症相关的通路(
P
<
0.01),主要涉及癌症通路、表皮生长因子受体(EGFR)酪氨酸激酶抑制剂耐药性、癌症中的转录调控异常、钙信号通路、Apelin信号通路、核苷酸结合寡聚化结构域(NOD)样受体信号通路等。实验表明五子衍宗丸具有抗睾丸炎症的作用,其机制可能是通过抑制NOD样受体蛋白3(NLRP3)炎症小体通路的激活来抑制炎症反应,一定程度上验证了网络药理学的预测结果。
结论
2
五子衍宗丸对睾丸炎症的抑制作用是多靶点、多途径、多机制的,该研究结果为五子衍宗丸的临床应用提供了一定证据支持。
Objective
2
To explore the anti-testicular inflammation mechanism of Wuzi Yanzongwan through network pharmacological analysis and experimental verification.
Method
2
The active ingredients of Wuzi Yanzongwan were searched in the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP), and their targets were predicted via SwissTargetPredicition. GeneCards and Online Mendelian Inheritance in Man (OMIM) were used to obtain the known targets for the treatment of testicular inflammation. STRING 11.0 was employed to construct the protein-protein interaction (PPI) network, and Cytoscape 3.7.1 to construct the “herbal medicine-active ingredient-target” network of Wuzi Yanzongwan and “active ingredient-disease target” network. Metascape was used for gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment of signaling pathways.
Result
2
A total of 72 active ingredients and 624 potential targets of Wuzi Yanzongwan were screened out, and 196 key targets were identified for the treatment of testicular inflammation by Wuzi Yanzongwan. The results of GO annotation showed that the anti-testicular inflammation targets of Wuzi Yanzongwan were involved in the biological processes such as the response to molecule of bacterial origin, the positive regulation of response to external stimulus, and the response to extracellular stimulus. KEGG pathway enrichment revealed that the major pathways associated with the treatment (
P
<
0.01) included the pathways in cancer, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor resistance, transcriptional misregulation in cancer, calcium signaling pathway, apelin signaling pathway, and NOD-like receptor signaling pathway. Wuzi Yanzongwan may exert the anti-testicular inflammation effect by inhibiting the activation of the NLR family pyrin domain-containing 3 (NLRP3) inflammasome pathway to alleviate the inflammatory response, which verifies the prediction results based on network pharmacology to a certain extent.
Conclusion
2
The inhibitory effect of Wuzi Yanzongwan on testicular inflammation is multi-target, multi-pathway, and multi-mechanism. The findings of this study provide evidence support for the clinical application of Wuzi Yanzongwan.
五子衍宗丸睾丸炎症网络药理学成分靶点信号通路
Wuzi Yanzongwantesticular inflammationnetwork pharmacologyingredienttargetsignaling pathway
HEDGER M P.Immunophysiology and pathology of inflammation in the testis and epididymis,2011[J].J Androl,2011,32(6):625-640.
AHMED A U.An overview of inflammation: Mechanism and consequences,2011[J].Frontiers in Biology,2011,6(4):274-281.
RACHEL B L.Male infertility: An overview of causes and treatment options,2016[J].Br J Nurs,2016,25(18):S35-S40.
AZENABOR A,EKUN A O,AKINLOYE O.Impact of inflammation on male reproductive tract,2015[J].J Reprod Infertil,2015,16(3):123-129.
周园.孕期增塑剂DBP暴露诱导子代小鼠睾丸炎症的机制研究[D].江苏:南京大学,2020.
李颖.睾丸炎中PK2通过NLRP3炎性小体通路促进IL-1β分泌影响雄性生育力的研究[D].武汉:华中科技大学,2019.
孔令青,李鸣镝.中医方剂“五子衍宗丸”组方的历史源流[J].中国中医基础医学杂志,2009,15(1):67-68.
李艳荣,樊慧杰,柴智,等.五子衍宗丸对帕金森病小鼠的神经保护及抗炎作用[J].中华中医药杂志,2020,35(7):3623-3626.
张若楠,柴智,樊慧杰,等.五子衍宗丸对实验性自身免疫性脑脊髓炎小鼠防治作用及其机制研究[J].中华中医药杂志,2018,33(4):1316-1319.
刘星,孙梦瀛,薛江源,等.五子衍宗丸对脱髓鞘模型炎症反应的抑制作用[J].中华中医药杂志,2021,36(5):2904-2908.
JINLONG R,PENG L,JINAN W,et al.TCMSP: A database of systems pharmacology for drug discovery from herbal medicines,2014[J].J Cheminform,2014,6(1):1-6.
SUNGHWAN K.Getting the most out of PubChem for virtual screening,2016[J].Expert Opin Drug Discov,2016,11(9):843-855.
DAINA A,MICHIELIN O,ZOETE V.SwissTargetPrediction: Updated data and new features for efficient prediction of protein targets of small molecules,2019[J].Nucleic Acids Res,2019,47(W1):W357-W364.
UniProt: the universal protein knowledgebase,2017[J].Nucleic Acids Res,2017,45(D1):D158-D169.
FRANZ M,LOPES C T,HUCK G,et al.Cytoscape.js: A graph theory library for visualisation and analysis,2016[J].Bioinformatics,2016,32(2):309-311.
SAFRAN M,DALAH I,ALEXANDER J,et al.GeneCards Version 3: The human gene integrator,2010[J].Database (Oxford),2010,2010(0):baq020.
HAMOSH A,SCOTT A F,AMBERGER J,et al.Online Mendelian Inheritance in Man (OMIM),a knowledgebase of human genes and genetic disorders,2002[J].Nucleic Acids Res,2002,30(1):52-55.
MERING C V,HUYNEN M,JAEGGI D,et al.STRING: A database of predicted functional associations between proteins,2003[J].Nucleic Acids Res,2003,31(1):258-261.
YINGYAO Z,BIN Z,LARS P,et al.Metascape provides a biologist-oriented resource for the analysis of systems-level datasets,2019[J].Nat Commun,2019,10(1):1523.
胡素芹,李悦,曹龑,等.五子衍宗丸对幼年大鼠睾丸支持细胞增殖的影响及机制[J].北京中医药大学学报,2017,40(11):917-922.
SUQIN H,DIANLONG L,CHUNRUI L,et al.Wuzi-Yanzong prescription alleviates spermatogenesis disorder induced by heat stress dependent on Akt,NF-κB signaling pathway,2021[J].Sci Rep,2021,11(1):18824.
杨卓,张希,陈志敏,等.五子衍宗丸中药物盐制后对肾精亏虚大鼠免疫功能的影响[J].时珍国医国药,2019,30(9):2134-2137.
王宁,张树成,陈西华,等.五子衍宗丸对无精症小鼠的免疫促进作用基因表达谱分析[J].上海中医药大学学报,2013,27(4):63-67.
MIAOMIAO G,FALIANG A,HAIYUAN Y,et al.Comparative effects of schisandrin A,B,and C on Propionibacterium acnes -induced,NLRP3 inflammasome activation-mediated IL-1β secretion and pyroptosis,2017[J].Biomed Pharmacother,2017,96:129-136.
MAARIT K,ELINA K,ELIN S,et al.Impact of dibenzocyclooctadiene lignans from Schisandra chinensis on the redox status and activation of human innate immune system cells,2018[J].Free Radic Biol Med,2018,131:309-317.
DONG E K,KYOUNG-JIN M,MIN-JONG K,et al.Hispidulin inhibits mast cell-mediated allergic inflammation through down-regulation of histamine release and inflammatory cytokines,2019[J].Molecules,2019,24(11):2131-2131.
REN X,HAN L,LI Y,et al.Isorhamnetin attenuates TNF-α-induced inflammation,proliferation,and migration in human bronchial epithelial cells via MAPK and NF-κB pathways,2021[J].Anat Rec (Hoboken),2021,304(4):901-913.
任改艳,张步有,黄剑林.槲皮素对LPS诱导小鼠RAW264.7细胞炎症的保护作用[J].中成药,2019,41(8):1795-1799.
ZHUANG Z,YE G,HUANG B.Kaempferol alleviates the Interleukin-1β-induced inflammation in rat osteoarthritis chondrocytes via suppression of NF-κB,2017[J].Med Sci Monit,2017,23:3925-3931.
BIAN Y,DONG Y,SUN J,et al.Protective effect of kaempferol on LPS-induced inflammation and barrier dysfunction in a coculture model of intestinal epithelial cells and intestinal microvascular endothelial cells,2020[J].J Agric Food Chem,2020,68(1):160-167.
BERRIDGE M J.The inositol trisphosphate/calcium signaling pathway in health and disease,2016[J].Physiol Rev,2016,96(4):1261-1296.
HIROSHI H,KYOSUKE U,NOBUYUKI K,et al.Apelin/apelin receptor system: Molecular characteristics,physiological roles,and prospects as a target for disease prevention and pharmacotherapy,2021[J].Curr Mol Pharmacol,2021,14(2):210-219.
PLATNICH J M,MURUVE D A.NOD-like receptors and inflammasomes: A review of their canonical and non-canonical signaling pathways,2019[J].Arch Biochem Biophys,2019,670(C):4-14.
ELLIOTT E I,SUTTERWALA F S.Initiation and perpetuation of NLRP3 inflammasome activation and assembly,2015[J].Immunol Rev,2015,265(1):35-52.
FOUAD A,ABDEL-AZIZ A,HAMOUDA A.Diacerein downregulates NLRP3/Caspase-1/IL-1β and IL-6/STAT3 pathways of inflammation and apoptosis in a rat model of cadmium testicular toxicity,2020[J].Biol Trace Elem Res,2020,195(2):499-505.
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