The Molecular Mechanism of Shufeng Jiedu Capsules in the Treatment of Influenza: A Comprehensive Analysis Based on Network Pharmacology, Bioinformatics, and Molecular Docking

Mengxia Yang , Chunming Zhao , Tengfei Chen , Xiaolong Xu , Qingquan Liu

›› 2024, Vol. 3 ›› Issue (3) : 160 -171.

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›› 2024, Vol. 3 ›› Issue (3) :160 -171. DOI: 10.14218/FIM.2024.00030
Original Article
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The Molecular Mechanism of Shufeng Jiedu Capsules in the Treatment of Influenza: A Comprehensive Analysis Based on Network Pharmacology, Bioinformatics, and Molecular Docking
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Abstract

Background and objectives Shufeng Jiedu Capsules (SFJD), a traditional Chinese medicine preparation, are widely used in the clinical treatment of influenza, yet their mechanism of action remains unclear. This study aimed to systematically explore the molecular mechanism of SFJD in the treatment of influenza using network pharmacology and bioinformatics techniques.

Methods The active ingredients of SFJD were retrieved from traditional Chinese medicine databases, and their targets were identified using the Swiss Target Prediction and TCMSP databases. Influenza disease genes were obtained from the GEO, GeneCards, and DisGeNET databases, and a Venn diagram was used to identify potential targets by mapping SFJD targets to influenza disease genes. Network construction and analysis of potential therapeutic targets were performed using the STRING12.0 database and Cytoscape3.9.1 software, leading to the identification of key targets. The expression of potential therapeutic targets in tissues and cells was retrieved using the BioGPS database. Functional enrichment analysis of these targets was conducted using the DAVID database. Molecular docking was then used to assess the interactions between key targets and core active ingredients.

Results SFJD contains 193 active ingredients and 985 targets. There are 510 influenza disease genes, 97 of which are potential therapeutic targets for SFJD in treating influenza, with 27 key targets identified through network construction and analysis. Tissue/cell-specific analysis revealed that 39 potential therapeutic targets are highly expressed in 37 specific tissues/cells. Functional enrichment analysis highlighted pathways such as the C-type lectin receptor signaling pathway, tumor necrosis factor signaling pathway, and hypoxia-inducible factor-1 signaling pathway. Molecular docking results indicated strong interactions between the core active ingredients and the key targets.

Conclusions This study systematically reveals that the mechanism of action of SFJD in treating influenza is complex, involving multiple targets and pathways related to antiviral, anti-inflammatory, and immune regulation effects. The findings provide valuable reference information for future clinical treatment and basic research on influenza.

Keywords

Shufeng Jiedu Capsules / Influenza / Network pharmacology / Bioinfor-matics / Molecular docking / Mechanism

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Mengxia Yang, Chunming Zhao, Tengfei Chen, Xiaolong Xu, Qingquan Liu. The Molecular Mechanism of Shufeng Jiedu Capsules in the Treatment of Influenza: A Comprehensive Analysis Based on Network Pharmacology, Bioinformatics, and Molecular Docking. , 2024, 3(3): 160-171 DOI:10.14218/FIM.2024.00030

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Acknowledgments

Not applicable.

Funding

This study was supported by the Key Discipline Construc-tion Project of Traditional Chinese Medicine authorized by the State Administration of Traditional Chinese Medicine (grant no. zyyzdxk-2023001) and the National Multidisciplinary Innovation Team Project of Traditional Chinese Medicine (grant no. ZYY-CXTD-D-202201).

Conflict of interest

QQL has served as Co-editor-in-Chief, and XLX has been an edi-torial board member of Future Integrative Medicine since Novem-ber 2021. The authors declare that they have no other competing interests.

Author contributions

Study concept and design (MXY), acquisition of data (CMZ), analysis and interpretation of data (MXY, CMZ, TFC), drafting of the manuscript (MXY), critical revision of the manuscript for important intellectual content (MXY, XLX, QQL), administrative, technical, or material support (XLX, QQL), and study supervision (XLX, QQL). All authors have made significant contributions to this study and have approved the final manuscript.

Data sharing statement

The data used to support the findings of this study are included in the article.

References

[1]

Labella AM, Merel SE. Influenza. Med Clin North Am 2013; 97(4):621-645. doi:10.1016/j.mcna.2013.03.001, PMID:23809717.

[2]

Gaitonde DY, Moore FC, Morgan MK. Influenza: Diagnosis and Treat-ment. Am Fam Physician 2019; 100(12):751-758. PMID:31845781.

[3]

Lam PP, Coleman BL, Green K, Powis J, Richardson D, Katz K, et al. Predictors of influenza among older adults in the emergency de-partment. BMC Infect Dis 2016; 16(1):615. doi:10.1186/s12879-016-1966-4,PMID:27793117.

[4]

Monto AS, Gravenstein S, Elliott M, Colopy M, Schweinle J. Clini-cal signs and symptoms predicting influenza infection. Arch Intern Med 2000; 160(21):3243-3247. doi:10.1001/archinte.160.21.3243,PMID:11088084.

[5]

Ohmit SE, Monto AS. Symptomatic predictors of influenza virus positivity in children during the influenza season. Clin Infect Dis 2006; 43(5):564-568. doi:10.1086/506352,PMID:16886147.

[6]

Minodier L, Charrel RN, Ceccaldi PE, van der Werf S, Blanchon T, Hanslik T, et al. Prevalence of gastrointestinal symptoms in patients with influenza, clinical significance, and pathophysiology of hu-man influenza viruses in faecal samples: what do we know? Virol J 2015; 12:215. doi:10.1186/s12985-015-0448-4,PMID:26651485.

[7]

Heo YA. Baloxavir: First Global Approval. Drugs 2018; 78(6):693-697. doi:10.1007/s40265-018-0899-1,PMID:29623652.

[8]

Gan K, Cheng Y, Chen Y, Tao L, Li F, Chen L. A retrospective study of traditional Chinese medicine combined with anti-influenza virus drugs in the treatment of influenza A J Changchun University Chi Med 2023; 39(2):171-174. doi:10.13463/j.cnki.cc-zyy.2023.02.013. (in Chinese).

[9]

Chen X, Ou Q. Effectiveness and safety of Lianhua Qingwen Granules and oseltamivir in the treatment of acute influenza. Western J of Tra-dit Chi Med 2023; 36(12):109-112.

[10]

Zhang L, Xue X, Liu G, Zhang L, Guan W, Chen X, et al. Similarities and differences between traditional Chinese medicine treatment of co-rona virus disease 2019 and influenza. J Practical Tradit Chin Internal Med 2021; 35(1):34-36. doi:10.13729/j.issn.1671-7813.z20200108.

[11]

Zhou F, Zhao G, Li B, Xu X, Shi Y, Mao Y, et al. Systematic review and meta-analysis of efficacy and safety of Shufeng Jiedu capsules in treatment of influenza. Chin J Chin Mater Med 2023; 48(22):6216-6224. doi:10.19540/j.cnki.cjcmm.20230804.501.

[12]

Liu Q, Chen T, Zhao G, Liu J. Clinical practice guideline of tradi-tional Chinese medicine for influenza (2021). J Tradit Chin Med 2022; 63(1):85-98. doi:10.13288/j.11-2166/r.2022.01.016.

[13]

Kumari R, Sharma SD, Kumar A, Ende Z, Mishina M, Wang Y, et al. Antiviral Approaches against Influenza Virus. Clin Microbiol Rev 2023; 36(1):e0004022. doi:10.1128/cmr.00040-22,PMID:36645300.

[14]

Dong Y.Study on the correlation between TCM syndrome types, con-stitution and blood routine of influenza [Dissertation]. Beijing: Beijing University of Chinese Medicine; 2018. (in Chinese)

[15]

Alam W, Khan H, Shah MA, Cauli O, Saso L. Kaempferol as a Dietary Anti-Inflammatory Agent: Current Therapeutic Standing. Mole-cules 2020; 25(18):4073. doi:10.3390/molecules25184073,PMID:32906577.

[16]

Periferakis A, Periferakis K, Badarau IA, Petran EM, Popa DC, Carun-tu A, et al. Kaempferol: Antimicrobial Properties, Sources, Clini-cal, and Traditional Applications. Int J Mol Sci 2022; 23(23):15054. doi:10.3390/ijms232315054,PMID:36499380.

[17]

Hytti M, Piippo N, Korhonen E, Honkakoski P, Kaarniranta K, Kaup-pinen A. Fisetin and luteolin protect human retinal pigment epi-thelial cells from oxidative stress-induced cell death and regulate inflammation. Sci Rep 2015; 5:17645. doi:10.1038/srep17645,PMID:26619957.

[18]

Bai L, Nong Y, Shi Y, Liu M, Yan L, Shang J, et al. Luteolin Inhibits Hepatitis B Virus Replication through Extracellular Signal-Regulated Kinase-Mediated Down-Regulation of Hepatocyte Nuclear Factor 4α Expression. Mol Pharm 2016; 13(2):568-577. doi:10.1021/acs.molpharmaceut.5b00789, PMID:26656210.

[19]

Yan J, Wang Q, Zheng X, Sun H, Zhou Y, Li D, et al. Luteolin enhanc-es TNF-related apoptosis-inducing ligand’s anticancer activity in a lung cancer xenograft mouse model. Biochem Biophys Res Com-mun 2012; 417(2):842-846. doi:10.1016/j.bbrc.2011.12.055,PMID:22206675.

[20]

Gong G, Guan YY, Zhang ZL, Rahman K, Wang SJ, Zhou S, et al. Isor-hamnetin: A review of pharmacological effects. Biomed Pharmaco-ther 2020;128:110301. doi:10.1016/j.biopha.2020.110301,PMID:32502837.

[21]

Periferakis A, Periferakis AT, Troumpata L, Periferakis K, Scheau AE, Savulescu-Fiedler I, et al. Kaempferol: A Review of Current Evi-dence of Its Antiviral Potential. Int J Mol Sci 2023; 24(22):16299. doi:10.3390/ijms242216299,PMID:38003488.

[22]

Yan H, Ma L, Wang H, Wu S, Huang H, Gu Z, et al. Luteolin de-creases the yield of influenza A virus in vitro by interfering with the coat protein I complex expression. J Nat Med 2019; 73(3):487-496. doi:10.1007/s11418-019-01287-7,PMID:30758716.

[23]

Liu AL, Liu B, Qin HL, Lee SM, Wang YT, Du GH. Anti-influenza virus activities of flavonoids from the medicinal plant Elsholtzia rugulo-sa. Planta Med 2008; 74(8):847-851. doi:10.1055/s-2008-1074558,PMID:18553272.

[24]

Abdal Dayem A, Choi HY, Kim YB, Cho SG. Antiviral effect of meth-ylated flavonol isorhamnetin against influenza. PLoS One 2015; 10 (3):e0121610. doi:10.1371/journal.pone.0121610,PMID:25806943.

[25]

Li J, Xu Y, Lin Z, Guan L, Chen S, Zhou L. Isorhamnetin inhibits ampli-fication of influenza A H1N1 virus inflammation mediated by inter-feron via the RIG-I/JNK pathway. Ann Transl Med 2021; 9(16):1327. doi:10.21037/atm-21-3532,PMID:34532464.

[26]

Yoshida Y, Niki E. Antioxidant effects of phytosterol and its compo-nents. J Nutr Sci Vitaminol (Tokyo) 2003; 49(4):277-280. doi:10.3177/jnsv.49.277,PMID:14598915.

[27]

Plat J, Hendrikx T, Bieghs V, Jeurissen ML, Walenbergh SM, van Gorp PJ, et al. Protective role of plant sterol and stanol esters in liver inflamma-tion: insights from mice and humans. PLoS One 2014; 9(10):e110758. doi:10.1371/journal.pone.0110758,PMID:25356831.

[28]

Kim KA, Lee IA, Gu W, Hyam SR, Kim DH. β-Sitosterol attenuates high-fat diet-induced intestinal inflammation in mice by inhibiting the binding of lipopolysaccharide to toll-like receptor 4 in the NF-κB pathway. Mol Nutr Food Res 2014; 58(5):963-972. doi:10.1002/mnfr.201300433,PMID:24402767.

[29]

Moon DO, Lee KJ, Choi YH, Kim GY. Beta-sitosterol-induced-apop-tosis is mediated by the activation of ERK and the downregulation of Akt in MCA-102 murine fibrosarcoma cells. Int Immunopharma-col 2007; 7(8):1044-1053. doi:10.1016/j.intimp.2007.03.010,PMID:17570321.

[30]

Zhou BX, Li J, Liang XL, Pan XP, Hao YB, Xie PF, et al. β-sitosterol ame-liorates influenza A virus-induced proinflammatory response and acute lung injury in mice by disrupting the cross-talk between RIG-I and IFN/STAT signaling. Acta Pharmacol Sin 2020; 41(9):1178-1196. doi:10.1038/s41401-020-0403-9,PMID:32504068.

[31]

Wang H, Xie Z, Fu F, Kang Y, Tian J, Zhang X, et al. Comparative study on innate immune molecules of A549 cells infected with in-fluenza A and B viruses. Chi J Immunology 2023; 39(8):1569-1572. doi:10.3969/j.issn.1000-484X.2023.08.001.

[32]

Datta SR, Brunet A, Greenberg ME. Cellular survival: a play in three Akts. Genes Dev 1999; 13(22):2905-2927. doi:10.1101/gad.13.22.2905,PMID:10579998.

[33]

Denisova OV, Söderholm S, Virtanen S, Von Schantz C, Bychkov D, Vashchinkina E, et al. Akt inhibitor MK2206 prevents influen-za pH1N1 virus infection in vitro. Antimicrob Agents Chemother 2014; 58(7):3689-3696. doi:10.1128/AAC.02798-13,PMID:24752266.

[34]

Zhirnov OP, Klenk HD. Control of apoptosis in influenza virus-in-fected cells by up-regulation of Akt and p53 signaling. Apoptosis 2007; 12(8):1419-1432. doi:10.1007/s10495-007-0071-y,PMID:17468837.

[35]

Eierhoff T, Hrincius ER, Rescher U, Ludwig S, Ehrhardt C. The epider-mal growth factor receptor (EGFR) promotes uptake of influenza A viruses (IAV) into host cells. PLoS Pathog 2010; 6(9):e1001099. doi:10.1371/journal.ppat.1001099,PMID:20844577.

[36]

Olsen CW, Kehren JC, Dybdahl-Sissoko NR, Hinshaw VS. bcl-2 al-ters influenza virus yield, spread, and hemagglutinin glycosylation. J Virol 1996; 70(1):663-666. doi:10.1128/JVI.70.1.663-666.1996, PMID:8523590.

[37]

Nencioni L, De Chiara G, Sgarbanti R, Amatore D, Aquilano K, Marcoc-ci ME, et al. Bcl-2 expression and p38MAPK activity in cells infected with influenza A virus: impact on virally induced apoptosis and viral replication. J Biol Chem 2009; 284(23):16004-16015. doi:10.1074/jbc.M900146200,PMID:19336399.

[38]

Wurzer WJ, Planz O, Ehrhardt C, Giner M, Silberzahn T, Pleschka S, et al. Caspase 3 activation is essential for efficient influenza virus propagation. EMBO J 2003; 22(11):2717-2728. doi:10.1093/emboj/cdg279,PMID:12773387.

[39]

Schütze S, Wiegmann K, Machleidt T, Krönke M. TNF-induced ac-tivation of NF-kappa B. Immunobiology 1995;193(2-4):193-203. doi:10.1016/s0171-2985(11)80543-7, PMID:8530143.

[40]

Pandey P, Al Rumaih Z, Kels MJT, Ng E, Kc R, Chaudhri G, et al. Targeting ec-tromelia virus and TNF/NF-κB or STAT3 signaling for effective treatment of viral pneumonia. Proc Natl Acad Sci U S A 2022; 119(8):e2112725119. doi:10.1073/pnas.2112725119,PMID:35177474.

[41]

Hu F, Mu R, Zhu J, Shi L, Li Y, Liu X, et al. Hypoxia and hypoxia-induci-ble factor-1α provoke toll-like receptor signalling-induced inflamma-tion in rheumatoid arthritis. Ann Rheum Dis 2014; 73(5):928-936. doi:10.1136/annrheumdis-2012-202444,PMID:23644550.

[42]

Semenza GL. HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations. J Clin Invest 2013; 123(9):3664-3671. doi:10.1172/JCI67230,PMID:23999440.

[43]

Li X, Shan C, Wu Z, Yu H, Yang A, Tan B. Emodin alleviated pul-monary inflammation in rats with LPS-induced acute lung injury through inhibiting the mTOR/HIF-1α/VEGF signaling pathway. In-flamm Res 2020; 69(4):365-373. doi:10.1007/s00011-020-01331-3,PMID:32130427.

[44]

Zou W, Chen D, Xiong M, Zhu J, Lin X, Wang L, et al. Insights into the increasing virulence of the swine-origin pandemic H1N1/ 2009 influenza virus. Sci Rep 2013; 3:1601. doi:10.1038/srep01601,PMID:23549303.

[45]

To EE, Broughton BR, Hendricks KS, Vlahos R, Selemidis S. Influenza A virus and TLR7 activation potentiate NOX2 oxidase-dependent ROS production in macrophages. Free Radic Res 2014; 48(8):940-947. doi :10.3109/10715762.2014.927579,PMID:24869957.

[46]

Zhang J, Miao J, Hou J, Lu C. The effects of H3N2 swine influenza vi-rus infection on TLRs and RLRs signaling pathways in porcine alveolar macrophages. Virol J 2015; 12:61. doi:10.1186/s12985-015-0284-6,PMID:26021751.

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