Network pharmacology-based prediction for therapeutic mechanism of FuYueKang Lotion on acute eczema
Main Article Content
Abstract
Objective: Fuyuekang Lotion (FYKL) is an improved traditional Chinese medicine (TCM) prescription widely used to treat acute eczema (AE). However, the mechanism of action remains unclear. This study aimed to explore the therapeutic mechanism of FYKL in AE.
Methods: We revealed the underlying mechanism by utilizing a network pharmacology approach, molecular docking studies, and in vitro verification. The active compounds in FYKL were identified, and their targets were predicted. These targets were subsequently mapped to a component-target interaction network, with their therapeutic mechanisms predicted through Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking was used to verify protein-binding efficacy. Potential key targets of FYKL against AE were further confirmed via reverse transcription quantitative polymerase chain reaction (RT-qPCR).
Results: The study identified 59 potential active compounds of FYKL, with quercetin, luteolin, and gallic acid suggested as critical active ingredients. Our findings suggest that these ingredients could exert their effects mainly by modulating the inflammatory immune response and promoting epidermal repair. FYKL was found to be a multi-target, multi-component drug that could potentially regulate the inflammatory immune response in AE through numerous pathways.
Conclusions: The findings from this study provide a scientific basis for further research into the therapeutic effects and mechanisms of FYKL in treating AE, underscoring the potential of TCM in modern therapeutics.
Article Details

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
References
- de Lusignan S, Alexander H, Broderick C, et al. The epidemiology of eczema in children and adults in England: A population-based study using primary care data. Clinical and Experimental Allergy. 2020, 51(3): 471-482. https://doi.org/10.1111/cea.13784
- Ellis CN, Drake LA, Prendergast MM, et al. Cost of atopic dermatitis and eczema in the United States. Journal of the American Academy of Dermatology. 2002, 46(3): 361-370. https://doi.org/10.1067/mjd.2002.120528
- Hay RJ, Johns NE, Williams HC, et al. The Global Burden of Skin Disease in 2010: An Analysis of the Prevalence and Impact of Skin Conditions. Journal of Investigative Dermatology. 2014, 134(6): 1527-1534. https://doi.org/10.1038/jid.2013.446
- Nowicki R, Trzeciak M, Wilkowska A, et al. Special paper Atopic dermatitis: current treatment guidelines. Statement of the experts of the Dermatological Section, Polish Society of Allergology, and the Allergology Section, Polish Society of Dermatology. Advances in Dermatology and Allergology. 2015, 4: 239-249. https://doi.org/10.5114/pdia.2015.53319
- Gu SX, Zhang AL, Coyle ME, et al. Chinese herbal medicine granules (PTQX) for children with moderate to severe atopic eczema: study protocol for a randomised controlled trial. Trials. 2015, 16(1). https://doi.org/10.1186/s13063-015-0806-y
- Wang Z, Wang ZZ, Geliebter J, Tiwari R, Li XM. Traditional Chinese medicine for food allergy and eczema. Annals of Allergy, Asthma and Immunology. 2021, 126(6): 639-654. https://doi.org/10.1016/j.anai.2020.12.002
- Zhang L, Lin S, Zheng Y, Wang H. Matrine Regulates Th1/Th2 Balance to Treat Eczema by Upregulating Interferon-$gamma$. Journal of Nanoscience and Nanotechnology. 2020, 20(6): 3378-3386. https://doi.org/10.1166/jnn.2020.17417
- Hwang SJ, Song YS, Lee HJ. Phaseolin Attenuates Lipopolysaccharide-Induced Inflammation in RAW 264.7 Cells and Zebrafish. Biomedicines. 2021, 9(4): 420. https://doi.org/10.3390/biomedicines9040420
- Zhou W, Hu M, Hu J, Du Z, Su Q, Xiang Z. Luteolin Suppresses Microglia Neuroinflammatory Responses and Relieves Inflammation-Induced Cognitive Impairments. Neurotoxicity Research. 2021, 39(6): 1800-1811. https://doi.org/10.1007/s12640-021-00426-x
- Zhang L, Lin S, Zheng Y. Observation on the efficacy of Fuyuekang lotion in the treatment of acute (subacute) eczema. Guangming Traditional Chinese Medicine. 2015, 30(5): 987-988.
- Chen S, Jiang H, Cao Y, et al. Drug target identification using network analysis: Taking active components in Sini decoction as an example. Scientific Reports. 2016, 6(1). https://doi.org/10.1038/srep24245
- Zhang R, Zhu X, Bai H, Ning K. Network Pharmacology Databases for Traditional Chinese Medicine: Review and Assessment. Frontiers in Pharmacology. 2019, 10. https://doi.org/10.3389/fphar.2019.00123
- Ru J, Li P, Wang J, et al. TCMSP: a database of systems pharmacology for drug discovery from herbal medicines. Journal of Cheminformatics. 2014, 6(1). https://doi.org/10.1186/1758-2946-6-13
- Xue R, Fang Z, Zhang M, Yi Z, Wen C, Shi T. TCMID: traditional Chinese medicine integrative database for herb molecular mechanism analysis. Nucleic Acids Research. 2012, 41(D1): D1089-D1095. https://doi.org/10.1093/nar/gks1100
- Kim S, Chen J, Cheng T, et al. PubChem 2019 update: improved access to chemical data. Nucleic Acids Research. 2018, 47(D1): D1102-D1109. https://doi.org/10.1093/nar/gky1033
- Ferreira LLG, Andricopulo AD. ADMET modeling approaches in drug discovery. Drug Discovery Today. 2019, 24(5): 1157-1165. https://doi.org/10.1016/j.drudis.2019.03.015
- Law V, Knox C, Djoumbou Y, et al. DrugBank 4.0: shedding new light on drug metabolism. Nucleic Acids Research. 2013, 42(D1): D1091-D1097. https://doi.org/10.1093/nar/gkt1068
- Chen X. TTD: Therapeutic Target Database. Nucleic Acids Research. 2002, 30(1): 412-415. https://doi.org/10.1093/nar/30.1.412
- Daina A, Michielin O, Zoete V. SwissTargetPrediction: updated data and new features for efficient prediction of protein targets of small molecules. Nucleic Acids Research. 2019, 47(W1): W357-W364. https://doi.org/10.1093/nar/gkz382
- Fu X, Mervin LH, Li X, et al. Toward Understanding the Cold, Hot, and Neutral Nature of Chinese Medicines Using in Silico Mode-of-Action Analysis. Journal of Chemical Information and Modeling. 2017, 57(3): 468-483. https://doi.org/10.1021/acs.jcim.6b00725
- Safran M, Dalah I, Alexander J, et al. GeneCards Version 3: the human gene integrator. Database. 2010, 2010(0): baq020-baq020. https://doi.org/10.1093/database/baq020
- Piñero J, Bravo À, Queralt-Rosinach N, et al. DisGeNET: a comprehensive platform integrating information on human disease-associated genes and variants. Nucleic Acids Research. 2016, 45(D1): D833-D839. https://doi.org/10.1093/nar/gkw943
- Hamosh A. Online Mendelian Inheritance in Man (OMIM), a knowledgebase of human genes and genetic disorders. Nucleic Acids Research. 2002, 30(1): 52-55. https://doi.org/10.1093/nar/30.1.52
- Davis AP, Grondin CJ, Johnson RJ, et al. Comparative Toxicogenomics Database (CTD): update 2021. Nucleic Acids Research. 2020, 49(D1): D1138-D1143. https://doi.org/10.1093/nar/gkaa891
- Szklarczyk D, Gable AL, Lyon D, et al. STRING v11: protein–protein association networks with increased coverage, supporting functional discovery in genome-wide experimental datasets. Nucleic Acids Research. 2018, 47(D1): D607-D613. https://doi.org/10.1093/nar/gky1131
- Chin CH, Chen SH, Wu HH, Ho CW, Ko MT, Lin CY. cytoHubba: identifying hub objects and sub-networks from complex interactome. BMC Systems Biology. 2014, 8(S4). https://doi.org/10.1186/1752-0509-8-s4-s11
- Shannon P, Markiel A, Ozier O, et al. Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks. Genome Research. 2003, 13(11): 2498-2504. https://doi.org/10.1101/gr.1239303
- Bader GD, Hogue CW. BMC Bioinformatics. 2003, 4(1): 2. https://doi.org/10.1186/1471-2105-4-2
- Huang DW, Sherman BT, Tan Q, et al. DAVID Bioinformatics Resources: expanded annotation database and novel algorithms to better extract biology from large gene lists. Nucleic Acids Research. 2007, 35(S2): W169-W175. https://doi.org/10.1093/nar/gkm415
- Pawar SS, Rohane SH. Review on Discovery Studio: An important Tool for Molecular Docking. Asian Journal Of Research in Chemistry. 2021, 14(1): 1-3. https://doi.org/10.5958/0974-4150.2021.00014.6
- Jin X, Awale M, Zasso M, Kostro D, Patiny L, Reymond JL. PDB-Explorer: a web-based interactive map of the protein data bank in shape space. BMC Bioinformatics. 2015, 16(1). https://doi.org/10.1186/s12859-015-0776-9
- Gagnon JK, Law SM, Brooks CL. Flexible CDOCKER: Development and application of a pseudo‐explicit structure‐based docking method within CHARMM. Journal of Computational Chemistry. 2015, 37(8): 753-762. https://doi.org/10.1002/jcc.24259
- Zheng J, Yao L, Zhou Y, et al. A novel function of NLRP3 independent of inflammasome as a key transcription factor of IL-33 in epithelial cells of atopic dermatitis. Cell Death and Disease. 2021, 12(10). https://doi.org/10.1038/s41419-021-04159-9
- Dehne N, Brüne B. HIF-1 in the inflammatory microenvironment. Experimental Cell Research. 2009, 315(11): 1791-1797. https://doi.org/10.1016/j.yexcr.2009.03.019
- Wu L, Zhang Q, Liang W, Ma Y, Niu L, Zhang L. Phytochemical Analysis Using UPLC-MSn Combined with Network Pharmacology Approaches to Explore the Biomarkers for the Quality Control of the Anticancer Tannin Fraction of Phyllanthus emblica L. Habitat in Nepal. Hu W, ed. Evidence-Based Complementary and Alternative Medicine. 2021, 2021: 1-19. https://doi.org/10.1155/2021/6623791
- Yang B, Kortesniemi M, Liu P, Karonen M, Salminen JP. Analysis of Hydrolyzable Tannins and Other Phenolic Compounds in Emblic Leafflower (Phyllanthus emblica L.) Fruits by High Performance Liquid Chromatography–Electrospray Ionization Mass Spectrometry. Journal of Agricultural and Food Chemistry. 2012, 60(35): 8672-8683. https://doi.org/10.1021/jf302925v
- Jafarinia M, Sadat Hosseini M, kasiri N, et al. Quercetin with the potential effect on allergic diseases. Allergy, Asthma and Clinical Immunology. 2020, 16(1). https://doi.org/10.1186/s13223-020-00434-0
- Lee HN, Shin SA, Choo GS, et al. Anti‑inflammatory effect of quercetin and galangin in LPS-stimulated RAW264.7 macrophages and DNCB‑induced atopic dermatitis animal models. International Journal of Molecular Medicine. Published online November 29, 2017. https://doi.org/10.3892/ijmm.2017.3296
- Mehrbani M, Choopani R, Fekri A, Mehrabani M, Mosaddegh M, Mehrabani M. The efficacy of whey associated with dodder seed extract on moderate-to-severe atopic dermatitis in adults: A randomized, double-blind, placebo-controlled clinical trial. Journal of Ethnopharmacology. 2015, 172: 325-332. https://doi.org/10.1016/j.jep.2015.07.003
- Gendrisch F, Esser PR, Schempp CM, Wölfle U. Luteolin as a modulator of skin aging and inflammation. BioFactors. 2020, 47(2): 170-180. https://doi.org/10.1002/biof.1699
- Kempuraj D, Thangavel R, Kempuraj DD, et al. Neuroprotective effects of flavone luteolin in neuroinflammation and neurotrauma. BioFactors. 2020, 47(2): 190-197. https://doi.org/10.1002/biof.1687
- Bai J, Zhang Y, Tang C, et al. Gallic acid: Pharmacological activities and molecular mechanisms involved in inflammation-related diseases. Biomedicine and Pharmacotherapy. 2021, 133: 110985. https://doi.org/10.1016/j.biopha.2020.110985
- Chan HHL, Ng T. Traditional Chinese Medicine (TCM) and Allergic Diseases. Current Allergy and Asthma Reports. 2020, 20(11). https://doi.org/10.1007/s11882-020-00959-9
- Diao Q, Liu Y. Diagnosis and Treatment of Hang Eczema: a Chinese Expert Consensus Statement (2020). Chinese Journal of Dermatovenereology of Integrated Traditional and Western Medicine, 2021, 20(5): 517-521.
- Shi DH, Dai YP, Su BZ, et al. Study on internal and external quality control methods of Platycladi Cacumen Carbonisata based on QAMS and color recognition. Zhongguo Zhong yao za zhi = Zhongguo zhongyao zazhi = China journal of Chinese materia medica, 2020, 45(24): 5996-6002.
- Darby IA, Hewitson TD. Hypoxia in tissue repair and fibrosis. Cell and Tissue Research. 2016, 365(3): 553-562. https://doi.org/10.1007/s00441-016-2461-3
- Manresa MC, Smith L, Casals-Diaz L, et al. Pharmacologic inhibition of hypoxia‐inducible factor (HIF)-hydroxylases ameliorates allergic contact dermatitis. Allergy. 2018, 74(4): 753-766. https://doi.org/10.1111/all.13655
- Sun L, Liu W, Zhang L juan. The Role of Toll-Like Receptors in Skin Host Defense, Psoriasis, and Atopic Dermatitis. Journal of Immunology Research. 2019, 2019: 1-13. https://doi.org/10.1155/2019/1824624