CC BY 4.0 · Pharmaceutical Fronts 2024; 06(03): e294-e304
DOI: 10.1055/s-0044-1789576
Original Article

Study on the Immunomodulatory effect of Qixian Decoction in an Asthmatic Mice Model Based on Serum Metabolomics

Manman Li#
1   National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Qingge Chen#
2   Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
,
Zhenhua Ni
2   Department of Respiratory Medicine, Putuo Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, People's Republic of China
,
Xinyi Le
1   National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
,
Tong Wu#
1   National Key Laboratory of Lead Druggability Research, Shanghai Institute of Pharmaceutical Industry Co., Ltd., China State Institute of Pharmaceutical Industry, Shanghai, People's Republic of China
› Author Affiliations
Funding This research was supported by a grant from the Special Project of the Shanghai 2020 “Science and Technology Innovation Action Plan” Biomedical Science and Technology by the Science and Technology Commission of Shanghai Municipality (Grant No. 20S21900700).

Abstract

The study aimed to investigate the immunomodulatory effect of Qixian Decoction (QXT) in an asthmatic model. In this study, ovalbumin (OVA)-induced asthma in female SPF BALB/c mice was established. Mice were randomly divided into four groups (n = 8): a control group, an OVA model group, a low-dose Qixian Granules (KLL) group, and a high-dose Qixian Granules (KLH) group. Mice in the KLL and KLH groups were given the Qixian Granules at a dose of 8 and 16 g/kg, respectively. After the treatment, the lung pathology was evaluated. The expression of inflammatory factors was determined. Serum metabolomics was used to investigate the overall regulation of QXT on the metabolism of asthmatic mice. Our data showed that QXT significantly increased the expression levels of Th1-related interferon-γ, Treg-related interleukin (IL)-10, and transforming growth factor-β1 while decreasing Th1-related tumor necrosis factor α levels in bronchoalveolar lavage fluid, and Th2-related IL-4 and IL-5 levels in serum when compared with the model group (all p < 0.05). Serum metabolomics revealed 28 potential biomarkers associated with nine pathways. Compared with the control group, 19 different metabolites in the KLL group and 18 different metabolites in the KLH were reversed. QXT's therapeutic effect against asthma might be related to glycerophospholipid metabolism and arachidonic acid metabolism. In conclusion, QXT could ameliorate inflammation of the OVA-induced asthmatic mice, mainly by regulating the expression of immune-related factors, probably through regulating the Th1/Th2 immune balance and promoting the proliferation of Treg.

Ethical Approval

This research was approved by the Institutional Animal Care and Use Committee of the Pharmacological Evaluation Research Center of the Shanghai Institute of Pharmaceutical Industry (Approval No. SYXK 2019–0027).


# The authors contributed equally to this work.




Publication History

Received: 03 March 2024

Accepted: 07 August 2024

Article published online:
03 September 2024

© 2024. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution License, permitting unrestricted use, distribution, and reproduction so long as the original work is properly cited. (https://creativecommons.org/licenses/by/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Masoli M, Fabian D, Holt S, Beasley R. Global Initiative for Asthma (GINA) Program. The global burden of asthma: executive summary of the GINA Dissemination Committee report. Allergy 2004; 59 (05) 469-478
  • 2 Huang K, Yang T, Xu J. et al; China Pulmonary Health (CPH) Study Group. Prevalence, risk factors, and management of asthma in China: a national cross-sectional study. Lancet 2019; 394 (10196): 407-418
  • 3 Agache I, Eguiluz-Gracia I, Cojanu C. et al. Advances and highlights in asthma in 2021. Allergy 2021; 76 (11) 3390-3407
  • 4 Yan X, Liu H, Li T. Lncrna NEAT1 regulates Th1/Th2 in pediatric asthma by targeting MicroRNA-217/GATA3. Iran J Public Health 2023; 52 (01) 106-117
  • 5 Chauhan A, Singh M, Agarwal A, Paul N. Correlation of TSLP, IL-33, and CD4+ CD25+ FOXP3+ T regulatory (Treg) in pediatric asthma. J Asthma 2015; 52 (09) 868-872
  • 6 Wang W, Yao Q, Teng F, Cui J, Dong J, Wei Y. Active ingredients from Chinese medicine plants as therapeutic strategies for asthma: overview and challenges. Biomed Pharmacother 2021; 137: 111383
  • 7 Zhang B, Li MY, Luo XM, Wang XB, Wu T. Analysis of the chemical components of Qixianqingming granules and their metabolites in rats by UPLC-ESI-Q-TOF-MS. J Mass Spectrom 2020; 55 (01) e4484
  • 8 Tang L, Zhu L, Zhang W. et al. Qi-xian decoction upregulated e-cadherin expression in human lung epithelial cells and ovalbumin-challenged mice by inhibiting reactive oxygen species-mediated extracellular-Signal-Regulated kinase (ERK) activation. Med Sci Monit 2020; 26: e922003-e1
  • 9 Li CX, Liu Y, Zhang YZ, Li JC, Lai J. Astragalus polysaccharide: a review of its immunomodulatory effect. Arch Pharm Res 2022; 45 (06) 367-389
  • 10 Xu F, Cui WQ, Wei Y. et al. Astragaloside IV inhibits lung cancer progression and metastasis by modulating macrophage polarization through AMPK signaling. J Exp Clin Cancer Res 2018; 37 (01) 207
  • 11 Hu L, Li L, Zhang H. et al. Inhibition of airway remodeling and inflammatory response by Icariin in asthma. BMC Complement Altern Med 2019; 19 (01) 316
  • 12 Qiu Y, Pan X, Hu Y. Polydatin ameliorates pulmonary fibrosis by suppressing inflammation and the epithelial mesenchymal transition via inhibiting the TGF-β/Smad signaling pathway. RSC Adv 2019; 9 (14) 8104-8112
  • 13 Yu HH, Zhao W, Zhang BX, Wang Y, Li J, Fang YF. Morinda officinalis extract exhibits protective effects against atopic dermatitis by regulating the MALAT1/miR-590–5p/CCR7 axis. J Cosmet Dermatol 2023; 22 (05) 1602-1612
  • 14 Kuraoka-Oliveira ÂM, Radai JAS, Leitão MM, Lima Cardoso CA, Silva-Filho SE, Leite Kassuya CA. Anti-inflammatory and anti-arthritic activity in extract from the leaves of Eriobotrya japonica. J Ethnopharmacol 2020; 249: 112418
  • 15 Shi J, Li R, Yang S, Phang Y, Zheng C, Zhang H. The protective effects and potential mechanisms of ligusticum chuanxiong: focus on anti-inflammatory, antioxidant, and antiapoptotic activities. Evid Based Complement Alternat Med 2020; 2020: 8205983
  • 16 Zhang H, Yue Y, Zhang Q. et al. Structural characterization and anti-inflammatory effects of an arabinan isolated from Rehmannia glutinosa Libosch. Carbohydr Polym 2023; 303: 120441
  • 17 Li J, Guo X, Luo Z. et al. Chemical constituents from the flowers of Inula japonica and their anti-inflammatory activity. J Ethnopharmacol 2024; 318 (Pt B): 117052
  • 18 Dong C. Cytokine regulation and function in T cells. Annu Rev Immunol 2021; 39: 51-76
  • 19 Hu P, Wang M, Gao H. et al. The role of helper T cells in psoriasis. Front Immunol 2021; 12: 788940
  • 20 Okuyama K, Wada K, Chihara J, Takayanagi M, Ohno I. Sex-related splenocyte function in a murine model of allergic asthma. Clin Exp Allergy 2008; 38 (07) 1212-1219
  • 21 Tang L, Chen Q, Meng Z. et al. Suppression of Sirtuin-1 increases IL-6 expression by activation of the Akt pathway during allergic asthma. Cell Physiol Biochem 2017; 43 (05) 1950-1960
  • 22 Acevedo N, Alashkar Alhamwe B, Caraballo L. et al. Perinatal and early-life nutrition, epigenetics, and allergy. Nutrients 2021; 13 (03) 724
  • 23 Komlósi ZI, van de Veen W, Kovács N. et al. Cellular and molecular mechanisms of allergic asthma. Mol Aspects Med 2022; 85: 100995
  • 24 Fahy JV. Type 2 inflammation in asthma–present in most, absent in many. Nat Rev Immunol 2015; 15 (01) 57-65
  • 25 Shieh YH, Huang HM, Wang CC, Lee CC, Fan CK, Lee YL. Zerumbone enhances the Th1 response and ameliorates ovalbumin-induced Th2 responses and airway inflammation in mice. Int Immunopharmacol 2015; 24 (02) 383-391
  • 26 Cerdá-Bernad D, Costa L, Serra AT. et al. Saffron against neuro-cognitive disorders: an overview of its main bioactive compounds, their metabolic fate and potential mechanisms of neurological protection. Nutrients 2022; 14 (24) 5368
  • 27 Chen X, Li XM, Gu W, Wang D, Chen Y, Guo XJ. LAT alleviates Th2/Treg imbalance in an OVA-induced allergic asthma mouse model through LAT-PLC-γ1 interaction. Int Immunopharmacol 2017; 44: 9-15
  • 28 Lloyd CM, Hawrylowicz CM. Regulatory T cells in asthma. Immunity 2009; 31 (03) 438-449
  • 29 Palomares O, Martín-Fontecha M, Lauener R. et al. Regulatory T cells and immune regulation of allergic diseases: roles of IL-10 and TGF-β. Genes Immun 2014; 15 (08) 511-520
  • 30 Böhm L, Maxeiner J, Meyer-Martin H. et al. IL-10 and regulatory T cells cooperate in allergen-specific immunotherapy to ameliorate allergic asthma. J Immunol 2015; 194 (03) 887-897
  • 31 Boonpiyathad T, Sözener ZC, Satitsuksanoa P, Akdis CA. Immunologic mechanisms in asthma. Semin Immunol 2019; 46: 101333
  • 32 Jiang DB, Zhou YD, Yang XQ. et al. Role of dendritic cells in the pathogenesis of asthma in children [in Chinese]. Zhonghua Er Ke Za Zhi 2004; 42 (07) 520-523
  • 33 Ryzhov S, Goldstein AE, Matafonov A, Zeng D, Biaggioni I, Feoktistov I. Adenosine-activated mast cells induce IgE synthesis by B lymphocytes: an A2B-mediated process involving Th2 cytokines IL-4 and IL-13 with implications for asthma. J Immunol 2004; 172 (12) 7726-7733
  • 34 Kuperman DA, Schleimer RP. Interleukin-4, interleukin-13, signal transducer and activator of transcription factor 6, and allergic asthma. Curr Mol Med 2008; 8 (05) 384-392
  • 35 Méndez-Enríquez E, Hallgren J. Mast cells and their progenitors in allergic asthma. Front Immunol 2019; 10: 821
  • 36 Peng B, Sun L, Zhang M. et al. Role of IL-25 on eosinophils in the initiation of Th2 responses in allergic asthma. Front Immunol 2022; 13: 842500
  • 37 Peebles Jr RS, Aronica MA. Proinflammatory pathways in the pathogenesis of asthma. Clin Chest Med 2019; 40 (01) 29-50
  • 38 Mazzarella G, Bianco A, Catena E, De Palma R, Abbate GF. Th1/Th2 lymphocyte polarization in asthma. Allergy 2000; 55 (Suppl. 61) 6-9
  • 39 Bellinghausen I, Khatri R, Saloga J. Current strategies to modulate regulatory T cell activity in allergic inflammation. Front Immunol 2022; 13: 912529
  • 40 Braga M, Quecchia C, Cavallucci E. et al. T regulatory cells in allergy. Int J Immunopathol Pharmacol 2011; 24 (1, suppl): 55S-64S
  • 41 Zeng C, Wen B, Hou G. et al. Lipidomics profiling reveals the role of glycerophospholipid metabolism in psoriasis. Gigascience 2017; 6 (10) 1-11
  • 42 Bansal P, Gaur SN, Arora N. Lysophosphatidylcholine plays critical role in allergic airway disease manifestation. Sci Rep 2016; 6 (01) 27430
  • 43 Oude Elferink RP, Bolier R, Beuers UH. Lysophosphatidic acid and signaling in sensory neurons. Biochim Biophys Acta 2015; 1851 (01) 61-65
  • 44 van der Veen JN, Kennelly JP, Wan S, Vance JE, Vance DE, Jacobs RL. The critical role of phosphatidylcholine and phosphatidylethanolamine metabolism in health and disease. Biochim Biophys Acta Biomembr 2017; 1859 (9, Pt B): 1558-1572
  • 45 Murphy RC, Gijón MA. Biosynthesis and metabolism of leukotrienes. Biochem J 2007; 405 (03) 379-395
  • 46 He R, Chen Y, Cai Q. The role of the LTB4–BLT1 axis in health and disease. Pharmacol Res 2020; 158: 104857
  • 47 Kanaoka Y, Austen KF. Roles of cysteinyl leukotrienes and their receptors in immune cell-related functions. Adv Immunol 2019; 142: 65-84