Effect of Shufeng Jiedu Capsules on the Production of Specific Antibodies against Influenza A H1N1 Virus and the Mechanisms

doi:10.19803/j.1672-8629.20250170

Abstract

Abstract: Objective To explore the effects of Shufeng Jiedu capsules (SFJD) on the humoral immune response in mice with non-lethal influenza A virus (H1N1) infection and the mechanisms using an in vitro model. Methods A mouse model of non-lethal H1N1 infection was established. Mice were randomly divided into the normal, PR8 model, positive drug oseltamivir-phosphate (27.5 mg·kg^-1·d^-1), SFJD medium-dose (1.144 g·kg^-1·d^-1), and SFJD high-dose groups (2.288 g·kg^-1·d^-1). Each group was then divided into five time-point subgroups: Days 0, 2, 4, 6, and 8. The drug was administered by gavage from day 0 to day 4. At each time point, the mice were euthanized for sample collection. Lung and body weights were measured to calculate the lung index. Total IgA, IgM, and IgG in bronchoalveolar lavage fluid were detected using a high-throughput liquid phase protein chip multiplex assay. H1N1-specific IgA, IgM, and IgG were measured via enzyme-linked immunosorbent assay (ELISA). On day 8, viral loads in lung tissues were assessed by real-time fluorescence quantitative PCR (Real-time PCR). Lung images were obtained using Micro-CT. The percentage of B cells in peripheral blood and bronchoalveolar lavage fluid was analyzed by flow cytometry. Human bronchi epithelial cells (BEAS-2B) were allocated into 6 groups: normal control, virus infection, positive drug (62.5 μmol·L^-1), SFJD high-dose (15.6 μg·mL^-1) and SFJD medium-dose (7.8 μg·mL^-1). Murine lung epithelial-12 cells (MLE12) were divided into five groups: normal control, virus infection, positive drug (250 μmol·L^-1), SFJD high-dose (62.5 μg·mL^-1) and SFJD medium-dose (31.3 μg·mL^-1). Western blot was employed to evaluate the impact of SFJD on expression levels of B cell activating factor (BAFF) in respiratory epithelial cells. Results SFJD reduced the lung index of H1N1 infected mice from day 4 to day 8 (P<0.05), viral load on day 8 (P<0.01), and alleviated inflammatory lesions. It increased the proportion of B cells in peripheral blood and lung tissues (P<0.01, P<0.001), decreased total IgA levels in bronchoalveolar lavage fluid on day 8, increased total IgM levels (P<0.01), and reduced specific IgA secretion on day 4 (P<0.0001) while promoting specific IgM (P<0.0001) and IgG (P<0.0001) secretion on day 8. SFJD also inhibited BAFF expression in respiratory epithelial cell lines (P<0.05, P<0.001). Conclusion Early administration of SFJD in case of H1N1 infection can restore the peripheral blood B cell proportion, promote their infiltration into lung tissues, enhance specific IgM and IgG secretion, and exert antiviral effects. Additionally, SFJD regulates the humoral immune response post-infection by inhibiting BAFF expression in respiratory epithelial cells and by preventing excessive B cell activation.

Key words: Influenza A Virus H1N1, Viral Pneumonia, Shufeng Jiedu Capsule, B-Cell Activating Factor, Specific Antibody

CLC Number:

LI Xinying, BAO Lei, LI Shuran, ZHAO Ronghua, SUN Jing, XIE Dan, BAO Yanyan, GUO Shanshan, CUI Xiaolan, GENG Zihan. Effect of Shufeng Jiedu Capsules on the Production of Specific Antibodies against Influenza A H1N1 Virus and the Mechanisms[J]. Chinese Journal of Pharmacovigilance, 2025, 22(8): 841-850.

Add to citation manager EndNote|Ris|BibTeX

URL: https://zgywjj.magtechjournal.com/EN/10.19803/j.1672-8629.20250170

https://zgywjj.magtechjournal.com/EN/Y2025/V22/I8/841

References

[1] IULIANO AD, ROGUSKI KM, CHANG HH, et al.Estimates of Global Seasonal Influenza-Associated Respiratory Mortality: a Modelling Study[J]. Lancet, 2018, 391(10127): 1285-1300.
[2] HEROLD S, BECKER C, RIDGE KM, et al.Influenza Virus-Induced Lung Injury: Pathogenesis and Implications for Treatment[J]. Eur Respir J, 2015, 45(5): 1463-1478.
[3] WANG X, GENG Z, BAO Y, et al.Shufeng Jiedu Capsule Alleviates Influenza A (H1N1) Virus Induced Acute Lung Injury by Regulating the Lung Inflammatory Microenvironment[J]. Heliyon, 2024, 10(12): e33237.
[4] XIA L, SHI Y, SU J, et al.Shufeng Jiedu, a Promising Herbal Therapy for Moderate COVID-19: Antiviral and Anti-Inflammatory Properties, Pathways of Bioactive Compounds, and a Clinical Real-World Pragmatic Study[J]. Phytomedicine, 2021, 85: 153390.
[5] General Office of the National Health Commission. Diagnosis and Treatment Protocol for Novel Coronavirus Infection (Trial Version 10)[EB/OL]. (2023-01-05)[2025-06-10]. https://www.gov.cn/zhengce/zhengceku/2023-01/06/content_5735343.htm.
[6] GENG ZH, BAO L, CAO S, et al. Shufeng Jiedu Capsule Alleviates Influenza Viral Pneumonia by Inhibiting the TLR/NF-κB Pathway in Respiratory Epithelial Cells[J]. Chinese Journal of Experimental Traditional Medical Formulae(中国实验方剂学杂志), (2024-12-24)[2025-06-10]. https://doi.org/10.13422/j.cnki.syfjx.20242241.
[7] MANDAL G, PRADHAN S.B Cell Responses and Antibody-Based Therapeutic Perspectives in Human Cancers[J]. Cancer Rep (Hoboken), 2024, 7(3): e2056.
[8] KESSLER S, STEGEN P, ZHAN S, et al.Jamaican Fruit Bats Mount a Stable and Highly Neutralizing Antibody Response after Bat Influenza Virus Infection[J]. Proc Natl Acad Sci US A, 2024, 121(42): e2413619121.
[9] KITTIKRAISAK W, TINOCO Y, LEVINE MZ, et al.The Added Value of Serologic Testing: a Comparison of Influenza Incidence among Pregnant Persons Based on Molecular-Based Surveillance Versus Serologic Testing[J]. Int J Infect Dis, 2024, 149: 107264.
[10] CHEN Y, CAI H, ZHANG Q, et al.Single-Cell Transcriptomic Analysis Reveals the Commonality of Immune Response upon H1N1 Influenza Virus Infection in Mice and Humans[J]. Animal Diseases, 2024, 4(1): 1-14.
[11] LI Y, ZOU H, MA L, et al.Fuzheng Jiedu Decoction Alleviates H1N1 Virus-Induced Acute Lung Injury in Mice by Suppressing the NLRP3 Inflammasome Activation[J]. J Ethnopharmacol, 2025, 341: 119314.
[12] CAO S, PANG B, XU YL, et al.Effects of Preventive Administration of Shufeng Jiedu Capsules on TLR4-Mediated Inflammatory Injury of Lung Tissue in Mouse Models of Influenza Virus Infection[J]. Chinese Journal of Pharmacovigilance(中国药物警戒), 2024, 21(1): 45-50.
[13] LEE D, JO H, JANG Y, et al.Alloferon and Zanamivir Show Effective Antiviral Activity against Influenza A Virus (H1N1) Infection in vitro and in vivo[J]. Int J Mol Sci, 2022, 24(1): 678.
[14] LI X, WANG M, LIU C, et al.Qingfeiyin Decoction Inhibits H1N1 Virus Infection via Modulation of Gut Microbiota and Inflammatory Pathways in a Murine Model[J]. Front Pharmacol, 2022, 13: 874068.
[15] SHI C, SU C, CEN L, et al.Vunakizumab-IL22, a Novel Fusion Protein, Promotes Intestinal Epithelial Repair and Protects against Gut Injury Induced by the Influenza Virus[J]. Biomedicines, 2023, 11(4): 1160.
[16] WEI X, SUN W, ZHU P, et al.Refined Polysaccharide from Dendro-bium Devonianum Resists H1N1 Influenza Viral Infection in Mice by Activating Immunity through the TLR4/MyD88/NF-kappaB Pathway[J]. Front Immunol, 2022, 13: 999945.
[17] GAO T, LIU J, HUANG N, et al.Sangju Cold Granule Exerts Anti-viral and Anti-Inflammatory Activities against Influenza A Virus in vitro and in vivo[J]. J Ethnopharmacol, 2024, 334: 118521.
[18] QUINTI I, MORTARI EP, FERNANDEZ SA, et al.IgA Antibodies and IgA Deficiency in SARS-CoV-2 Infection[J]. Front Cell Infect Microbiol, 2021, 11: 655896.
[19] REIS LR, SILVA-MORAES V, TEIXEIRA-CARVALHO A, et al.B-Cell Dynamics Underlying Poor Response upon Split-Inactivated Influenza Virus Vaccination[J]. Front Immunol, 2024, 15: 1481910.
[20] BAO K, ZHANG J, SCHERL A, et al.Activation-Induced Cytidine Deaminase Impacts the Primary Antibody Repertoire in Naive Mice[J]. J Immunol, 2022, 208(12): 2632-2642.
[21] PAN M, ZHAO H, JIN R, et al.Targeting Immune Checkpoints in Anti-Neutrophil Cytoplasmic Antibodies Associated Vasculitis: the Potential Therapeutic Targets in the Future[J]. Front Immunol, 2023, 14: 1156212.
[22] DE GRUIJTER NM, JEBSON B, ROSSER EC.Cytokine Production by Human B Cells: Role in Health and Autoimmune Disease[J]. Clin Exp Immunol, 2022, 210(3): 253-262.
[23] LIU L, WEI Q, LIN Q, et al.Anti-Spike IgG Causes Severe Acute Lung Injury by Skewing Macrophage Responses during Acute SARS-CoV Infection[J]. JCI Insight, 2019, 4(4): e123158.
[24] BATOOL S, CHOKKAKULA S, SONG MS.Influenza Treatment: Limitations of Antiviral Therapy and Advantages of Drug Combination Therapy[J]. Microorganisms, 2023, 11(1): 183.
[25] LU CL, YANG LQ, JIN XY, et al.Chinese Herbal Medicine Shufeng Jiedu Capsule for Mild to Moderate COVID-19: a Multicenter, Randomized, Double-Blind, Placebo-Controlled Phase II Trial[J]. Front Pharmacol, 2024, 15: 1383831.
[26] HAN Y, XU J, ZHU Q, et al.Study on Basic and Clinical Application of Shufeng Jiedu Capsule in Treating Respiratory Tract Infection[J]. Chin Med, 2023, 18(1): 45.
[27] JONES JC, YEN HL, ADAMS P, et al.Influenza Antivirals and Their Role in Pandemic Preparedness[J]. Antiviral Res, 2023, 210: 105499.
[28] BAO L, GENG ZH, CUI XL. Shufeng Jiedu Capsules Regulate the TLR4/TRIF/TBK1 Signaling Pathway to Improve Pulmonary Inflammation in Mice Infected with Human Coronavirus 229E[J]. Chinese Journal of Experimental Traditional Medical Formulae (中国实验方剂学杂志), (2025-01-15)[2025-06-10]. https://doi.org/10.13422/j.cnki.syfjx.20242345.
[29] LI ZH, ZHANG H, CHEN JL, et al.Shufeng Jiedu Capsule Exerted a Protective Effect on Mice with Influenza A Virus H1N1 Pneumonia Model through the miR-155/JAK1-STAT1 Signaling Pathway[J]. Chinese Journal of Pathophysiology(中国病理生理杂志), 2022, 38(7):1219-1225.
[30] RASTOGI I, JEON D, MOSEMAN JE, et al.Role of B Cells as Antigen Presenting Cells[J]. Front Immunol, 2022, 13: 954936.
[31] TANGYE S G, MACKIE J, PATHMANANDAVEL K, et al.The Trajec-tory of Human B-Cell Function, Immune Deficiency, and Allergy Revealed by Inborn Errors of Immunity[J]. Immunol Rev, 2024, 322(1): 212-232.
[32] YU X, ZHANG X, ZHAO B, et al.Intensive Cytokine Induction in Pandemic H1N1 Influenza Virus Infection Accompanied by Robust Production of IL-10 and IL-6[J]. PLoS One, 2011, 6(12): e28680.
[33] FU Y, YU B, WANG Q, et al.Oxidative Stress-Initiated One-Carbon Metabolism Drives the Generation of Interleukin-10-Producing B Cells to Resolve Pneumonia[J]. Cell Mol Immunol, 2024, 21(1): 19-32.
[34] WANG C, YANG S, HUANG X, et al.TGF-Beta1 Reduces the Diffe-rentiation of Porcine IgA-Producing Plasma Cells by Inducing IgM(+) B Cells Apoptosis via Bax/Bcl2-Caspase3 Pathway[J]. FASEB J, 2023, 37(10): e23180.
[35] SHARP TH, BOYLE AL, DIEBOLDER CA, et al.Insights into IgM-Mediated Complement Activation Based on in Situ Structures of IgM-C1-C4b[J]. Proc Natl Acad Sci USA, 2019, 116(24): 11900-11905.
[36] WEGMAN AD, WALDRAN MJ, BAHR LE, et al.DENV-Specific IgA Contributes Protective and Non-Pathologic Function during Antibody-Dependent Enhancement of DENV Infection[J]. PLoS Pathog, 2023, 19(8): e1011616.
[37] MES L, STEFFEN U, CHEN HJ, et al.IgA2 Immune Complexes Selectively Promote Inflammation by Human CD103(+) Dendritic Cells[J]. Front Immunol, 2023, 14: 1116435.
[38] GONG S, RUPRECHT RM.Immunoglobulin M: an Ancient Antiviral Weapon-Rediscovered[J]. Front Immunol, 2020, 11: 1943.
[39] KRAMMER F.The Human Antibody Response to Influenza A Virus Infection and Vaccination[J]. Nat Rev Immunol, 2019, 19(6): 383-397.
[40] ROBAK OH, HEIMESAAT MM, KRUGLOV AA, et al.Antibiotic Treatment-Induced Secondary IgA Deficiency Enhances Susceptibility to Pseudomonas Aeruginosa Pneumonia[J]. J Clin Invest, 2018, 128(8): 3535-3545.
[41] SCHWEIGHOFFER E, TYBULEWICZ VL.BAFF Signaling in Health and Disease[J]. Curr Opin Immunol, 2021, 71: 124-131.
[42] TURIANOVA L, LACHOVA V, SVETLIKOVA D, et al.Comparison of Cytokine Profiles Induced by Nonlethal and Lethal Doses of Influenza A Virus in Mice[J]. Exp Ther Med, 2019, 18(6): 4397-4405.