Identifying Synergistic Mechanisms of Multiple Ingredients in Shuangbai Tablets against Proteinuria by Virtual Screening and a Network Pharmacology Approach

被引:4
作者
Ma, Xiaoqin [1 ]
Yu, Meixiang [1 ]
Hao, Chenxia [1 ]
Yang, Wanhua [1 ,2 ]
机构
[1] Shanghai Jiao Tong Univ, Sch Med, Ruijin Hosp, Dept Pharm, Shanghai 200025, Peoples R China
[2] Shanghai Jiao Tong Univ, Med Sch, Ruijin Hosp North, Dept Pharm, Shanghai 201801, Peoples R China
关键词
CHRONIC KIDNEY-DISEASE; TRADITIONAL CHINESE MEDICINE; ALDOSTERONE SYSTEM BLOCKADE; GLOMERULAR-FILTRATION-RATE; ENDOTHELIAL GROWTH-FACTOR; AMELIORATES RENAL INJURY; RENIN-ANGIOTENSIN SYSTEM; INDUCED PODOCYTE INJURY; ALL-CAUSE MORTALITY; CARDIOVASCULAR-DISEASE;
D O I
10.1155/2020/1027271
中图分类号
R [医药、卫生];
学科分类号
10 ;
摘要
Shuangbai Tablets (SBT), a traditional herbal mixture, has shown substantial clinical efficacy. However, a systematic mechanism of its active ingredients and pharmacological mechanisms of action against proteinuria continues being lacking. A network pharmacology approach was effectual in discovering the relationship of multiple ingredients and targets of the herbal mixture. This study aimed to identify key targets, major active ingredients, and pathways of SBT against proteinuria by network pharmacology approach combined with thin layer chromatography (TLC). Human phenotype (HP) disease analysis, gene ontology (GO) analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and molecular docking were used in this study. To this end, a total of 48 candidate targets of 118 active ingredients of SBT were identified. Network analysis showed PTGS2, ESR1, and NOS2 to be the three key targets, and beta-sitosterol, quercetin, and berberine were the three major active ingredients; among them one of the major active ingredients, quercetin, was discriminated by TLC. These results of the functional enrichment analysis indicated that the most relevant disease including these 48 candidate proteins is proteinuria, SBT treated proteinuria by sympathetically regulating multiple biological pathways, such as the HIF-1, RAS, AGE-RAGE, and VEGF signaling pathways. Additionally, molecular docking validation suggested that major active ingredients of SBT were capable of binding to HIF-1A and VEGFA of the main pathways. Consequently, key targets, major active ingredients, and pathways based on data analysis of SBT against proteinuria were systematically identified confirming its utility and providing a new drug against proteinuria.
引用
收藏
页数:15
相关论文
共 108 条
  • [1] Albumin-induced podocyte injury and protection are associated with regulation of COX-2
    Agrawal, Shipra
    Guess, Adam J.
    Chanley, Melinda A.
    Smoyer, William E.
    [J]. KIDNEY INTERNATIONAL, 2014, 86 (06) : 1150 - 1160
  • [2] Amberger J. S., 2017, CURRENT PROTOCOLS BI, V58
  • [3] Gene network analysis reveals the association of important functional partners involved in antibiotic resistance: A report on an important pathogenic bacterium Staphylococcus aureus
    Anitha, P.
    Anbarasu, Anand
    Ramaiah, Sudha
    [J]. GENE, 2016, 575 (02) : 253 - 263
  • [4] UniProt: the universal protein knowledgebase
    Bateman, Alex
    Martin, Maria Jesus
    O'Donovan, Claire
    Magrane, Michele
    Alpi, Emanuele
    Antunes, Ricardo
    Bely, Benoit
    Bingley, Mark
    Bonilla, Carlos
    Britto, Ramona
    Bursteinas, Borisas
    Bye-A-Jee, Hema
    Cowley, Andrew
    Da Silva, Alan
    De Giorgi, Maurizio
    Dogan, Tunca
    Fazzini, Francesco
    Castro, Leyla Garcia
    Figueira, Luis
    Garmiri, Penelope
    Georghiou, George
    Gonzalez, Daniel
    Hatton-Ellis, Emma
    Li, Weizhong
    Liu, Wudong
    Lopez, Rodrigo
    Luo, Jie
    Lussi, Yvonne
    MacDougall, Alistair
    Nightingale, Andrew
    Palka, Barbara
    Pichler, Klemens
    Poggioli, Diego
    Pundir, Sangya
    Pureza, Luis
    Qi, Guoying
    Rosanoff, Steven
    Saidi, Rabie
    Sawford, Tony
    Shypitsyna, Aleksandra
    Speretta, Elena
    Turner, Edward
    Tyagi, Nidhi
    Volynkin, Vladimir
    Wardell, Tony
    Warner, Kate
    Watkins, Xavier
    Zaru, Rossana
    Zellner, Hermann
    Xenarios, Ioannis
    [J]. NUCLEIC ACIDS RESEARCH, 2017, 45 (D1) : D158 - D169
  • [5] Chronic inhibition of NOS-2 ameliorates renal injury, as well as COX-2 and TGF-β1 overexpression in 5/6 nephrectomized rats
    Bautista-Garcia, Pablo
    Sanchez-Lozada, Laura Gabriela
    Cristobal-Garcia, Magdalena
    Tapia, Edilia
    Soto, Virgilia
    Avila-Casado, Ma. Carmen
    Marquez-Velasco, Ricardo
    Bojalil, Rafael
    Franco, Martha
    Herrera-Acosta, Jaime
    [J]. NEPHROLOGY DIALYSIS TRANSPLANTATION, 2006, 21 (11) : 3074 - 3081
  • [6] Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: An update
    Bhattacharjee, Niloy
    Barma, Sujata
    Konwar, Nandita
    Dewanjee, Saikat
    Manna, Prasenjit
    [J]. EUROPEAN JOURNAL OF PHARMACOLOGY, 2016, 791 : 8 - 24
  • [7] Hypoxia-inducible-factor-1 in trauma and critical care
    Bogdanovski, Dorian A.
    DiFazio, Louis T.
    Bogdanovski, Anastasia K.
    Csoka, Balazs
    Jordan, Garrett B.
    Paul, Elina R.
    Antonioli, Luca
    Pilip, Stefanie A.
    Nemeth, Zoltan H.
    [J]. JOURNAL OF CRITICAL CARE, 2017, 42 : 207 - 212
  • [8] Brysbaert G., 2017, BIOINFORMATICS, V34
  • [9] Burley SK, 2017, METHODS MOL BIOL, V1606, P627, DOI 10.1007/978-1-4939-7000-1_26
  • [10] Yinchenhao decoction suppresses rat liver fibrosis involved in an apoptosis regulation mechanism based on network pharmacology and transcriptomic analysis
    Cai, Fei-Fei
    Bian, Yan-Qin
    Wu, Rong
    Sun, Yang
    Chen, Xiao-Le
    Yang, Meng-Die
    Zhang, Qian-ru
    Hu, Yuanjia
    Sun, Ming-Yu
    Su, Shi-Bing
    [J]. BIOMEDICINE & PHARMACOTHERAPY, 2019, 114