Objective To explore the molecular mechanism of benzo[a]pyrene (BaP) in inducing allergic asthma (AA), reveal its key functional targets and core regulatory pathways, and provide theoretical support for the environmental prevention and targeted intervention of AA.

Methods An integrated strategy of network toxicology and molecular docking was applied. BaP-related targets were screened via databases including SwissTargetPrediction and ChEMBL, while AA-associated genes were collected from GeneCards and OMIM databases. After obtaining the intersection targets using the Venny website, protein-protein interaction (PPI) analysis, Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were conducted. The binding affinity between BaP and core targets was subsequently verified with AutoDock Vina software.

Results The toxicity prediction results showed that BaP exhibits strong respiratory toxicity. A total of 111 intersection targets of BaP and AA were screened, with TNF, CXCL8, CCL2, etc. identified as core targets. KEGG enrichment analysis indicated that these intersection targets were significantly enriched in inflammation-related pathways including MAPK, NF-κB and TNF signaling pathways. Molecular docking results showed that BaP had strong binding capacity with all core targets (binding energies were less than - 5.0 kcal/mol), with the most stable binding to CXCR4 (-11.5 kcal/mol).

Conclusion BaP binds to core targets with high affinity, activates multiple inflammatory pathways, forms a "multi-target-multi-pathway" regulatory network, and induces airway inflammation and remodeling. This study provides a theoretical basis for the environmental prevention and targeted intervention of AA.

1. TanT, YangF, WangZ, et al. Mediated Mendelian randomization analysis to determine the role of immune cells in regulating the effects of plasma metabolites on childhood asthma[J]. Medicine (Baltimore), 2024, 103(30): e38957. DOI: 10.1097/MD.0000000000038957.

2. HosseiniSA, ShateriZ, AbolnezhadianF, et al. Does pomegranate extract supplementation improve the clinical symptoms of patients with allergic asthma? A double-blind, randomized, placebo-controlled trial[J]. Front Pharmacol, 2023, 14: 1109966. DOI: 10.3389/fphar.2023.1109966.

3. XuZ, MaH, LiuY, et al. Analysis of intestinal microorganisms and metabolite in childhood allergic asthma: role in assessing the severity of condition in children[J]. Front Pediatr, 2025, 13: 1680620. DOI: 10.3389/fped.2025.1680620.

4. DongB, XieL, LiY. Exploring the therapeutic role of natural products in allergic rhinitis based on pathophysiology and signaling pathways[J]. J Asthma Allergy, 2025, 18: 1551-1584. DOI: 10.2147/JAA.S550615.

5. SongW, NiS, FuY, et al. Uncovering the mechanism of Maxing Ganshi decoction on asthma from a systematic perspective: a network pharmacology study[J]. Sci Rep, 2018, 8(1): 17362. DOI: 10.1038/s41598-018-35791-9.

6. WangE, LiuX, TuW, et al. Benzo(a)pyrene facilitates dermatophagoides group 1 (Der f 1)-induced epithelial cytokine release through aryl hydrocarbon receptor in asthma[J]. Allergy, 2019, 74(9): 1675-1690. DOI: 10.1111/all.13784.

7. BulutB, RiganoL, DoriaHB, et al. A multigenerational study can detect the evolutionary response to BaP exposure in the non-biting freshwater midge Chironomus riparius[J]. Chemosphere, 2024, 358: 142242. DOI: 10.1016/j.chemosphere.2024.142242.

8. LeiQ, DuC, MaY, et al. Identifying piRNAs that regulate BaP-induced lung injuries: a bottom-up approach from toxicity pathway investigation to animal validation[J]. Ecotoxicol Environ Saf, 2024, 277: 116330. DOI: 10.1016/j.ecoenv.2024.116330.

9. YanagisawaR, KoikeE, Win-ShweTT, et al. Effects of lactational exposure to low-dose BaP on allergic and non-allergic immune responses in mice offspring[J]. J Immunotoxicol, 2018, 15(1): 31-40. DOI: 10.1080/1547691X.2018.1442379.

10. DuB, XiaoX, WangH, et al. Evaluation of the impact of BaP exposure on the gut microbiota and allergic responses in an OVA-sensitized mouse model[J]. Environ Health Perspect, 2023, 131(6): 67004. DOI: 10.1289/EHP11874.

11. ZouH, DuanJ, XieY, et al. Benzo[a]pyrene exacerbates allergen-induced airway inflammation through NLRP3-dependent dendritic cell activation and pathogenic T helper cell polarization[J]. Front Immunol, 2025, 16: 1699886. DOI: 10.3389/fimmu.2025.1699886.

12. RanS, GuD, ZhaoY, et al. Integrated network toxicology, molecular docking, molecular dynamics simulation, and experimental verification to elucidate the mechanism of hepatotoxicity and processing detoxification in Fructus Meliae Toosendan[J]. Toxicon, 2026, 271: 108933. DOI: 10.1016/j.toxicon.2025.108933.

13. XuK, ZhangQ, ShenZ, et al. Analysis of toxicity and mechanisms of aspartame in kidney stones with network toxicology and molecular docking strategy[J]. Sci Rep, 2025, 15(1): 45563. DOI: 10.1038/s41598-025-29822-5.

14. FanZ, DuH, ZhouX, et al. Network toxicology and molecular docking reveal the toxicological mechanisms of DEHP in bone diseases[J]. Int J Mol Sci, 2025, 26(22): 10895. DOI: 10.3390/ijms262210895.

15. ZhangM, LvX, WangC, et al. Molecular mechanisms of dose-dependent regulation of hepatic lipid metabolism by BaP through modulation of AhR binding to XRE1 or XRE3[J]. Front Pharmacol, 2025, 16: 1595566. DOI: 10.3389/fphar.2025.1595566.

16. LindnerK, WeberingS, StroebeleM, et al. Low dose carbon black nanoparticle exposure does not aggravate allergic airway inflammation in mice irrespective of the presence of surface polycyclic aromatic hydrocarbons[J]. Nanomaterials (Basel), 2018, 8(4): 213. DOI: 10.3390/nano8040213.

17. ChowdhuryPH, KitamuraG, HondaA, et al. Synergistic effect of carbon nuclei and polyaromatic hydrocarbons on respiratory and immune responses[J]. Environ Toxicol, 2017, 32(9): 2172-2181. DOI: 10.1002/tox.22430.

18. NamakanovaOA, GorshkovaEA, ZvartsevRV, et al. Therapeutic potential of combining IL-6 and TNF blockade in a mouse model of allergic asthma[J]. Int J Mol Sci, 2022, 23(7): 3521. DOI: 10.3390/ijms23073521.

19. LechnerA, HenkelFDR, HartungF, et al. Macrophages acquire a TNF-dependent inflammatory memory in allergic asthma[J]. J Allergy Clin Immunol, 2022, 149(6): 2078-2090. DOI: 10.1016/j.jaci.2021.11.026.

20. MasoodO, KumarS, KantS, et al. Association of polymorphisms of antioxidants (GSTM1/T1) and inflammation-related genes (CXCL8, IL-33, and IL-6) with chronic obstructive pulmonary disease (COPD) [J]. J Appl Genet, 2025, DOI: 10.1007/s13353-025-01016-9.

21. KimHJ, DinhDTT, YangJ, et al. High sucrose intake exacerbates airway inflammation through pathogenic Th2 and Th17 response in ovalbumin (OVA)-induced acute allergic asthma in C57BL/6 mice[J]. J Nutr Biochem, 2024, 124: 109504. DOI: 10.1016/j.jnutbio.2023.109504.

22. De VolderJ, BontinckA, De GroveK, et al. Trajectory of neutrophilic responses in a mouse model of pollutant-aggravated allergic asthma[J]. Environ Pollut, 2023, 329: 121722. DOI: 10.1016/j.envpol.2023.121722.

23. LiY, ChenZ, HanM, et al. Plasmacytoid dendritic cells alleviate allergic asthma via airway epithelial cell-dependent thymosin β4 expression[J]. J Allergy Clin Immunol, 2025, 156(1): 171-185. DOI: 10.1016/j.jaci.2025.01.047.

24. ChengM, ShangPP, WeiDD, et al. Modulation of lung CD11b⁺ dendritic cells by acupuncture alleviates Th2 airway inflammation in allergic asthma[J]. Chin Med, 2025, 20(1): 67. DOI: 10.1186/s13020-025-01119-9.

25. ZhangHL, ZhangHY, WangL, et al. Bioinformatics and network pharmacology identify the therapeutic role of guominkang in allergic asthma by inhibiting PI3K/Akt signaling[J]. J Inflamm Res, 2025, 18: 2805-2821. DOI: 10.2147/JIR.S484251.

26. BernauK, LeetJP, FloerkeH, et al. Interleukin-1α is a critical mediator of the response of human bronchial fibroblasts to eosinophilic inflammation[J]. Cells, 2021, 10(3): 528. DOI: 10.3390/cells10030528.

27. DingZ, DowlingMR, Wade-VallanceAK, et al. Long-lived IgE plasma cells persist in secondary lymphoid tissues using a navitoclax-sensitive survival program[J]. Immunity, 2025, 58(11): 2704-2716. DOI: 10.1016/j.immuni.2025.10.006.

28. ImpellizzieriD, RidderF, RaeberME, et al. IL-4 receptor engagement in human neutrophils impairs their migration and extracellular trap formation[J]. J Allergy Clin Immunol, 2019,  144(1): 267-279. DOI: 10.1016/j.jaci.2019.01.042.

29. LuX, JiS, LiuJ, et al. Benzo(a)pyrene aggregating lung inflammation via inducing IL1R1 expression in asthma: insights from network toxicology, single-cell transcriptomics, and Mendelian randomization[J]. Ecotoxicol Environ Saf, 2026, 321: 120415. DOI: 10.1016/j.ecoenv.2026.120415.

30. Vázquez-GómezG, Rocha-ZavaletaL, Rodríguez-SosaM, et al. Benzo[a]pyrene activates an AhR/Src/ERK axis that contributes to CYP1A1 induction and stable DNA adducts formation in lung cells[J]. Toxicol Lett, 2018, 289: 54-62. DOI: 10.1016/j.toxlet.2018.03.012.

31. ZhaoH, FuL, XiangHX, et al. N-acetylcysteine alleviates pulmonary inflammatory response during benzo[a]pyrene-evoked acute lung injury[J]. Environ Sci Pollut Res Int, 2022, 29(3): 3474-3486. DOI: 10.1007/s11356-021-15914-y.

32. ZhangZQ, BaoYW, WangH, et al. Artesunate alleviates chronic allergic rhinitis and asthma syndrome via the CCR3/NF-κB pathway: a comprehensive analysis[J]. Int Immunopharmacol, 2025, 166: 115562. DOI: 10.1016/j.intimp.2025.115562.

33. AlwanianWM. Fisetin mitigates chronic lung injury induced by benzo(a)pyrene by regulation of inflammation and oxidative stress[J]. Curr Issues Mol Biol, 2025, 47(3): 209. DOI: 10.3390/cimb47030209.

34. HeL, YinR, HangW, et al. Oxygen glucose deprivation-induced lactylation of H3K9 contributes to M1 polarization and inflammation of microglia through TNF pathway[J]. Biomedicines, 2024, 12(10): 2371. DOI: 10.3390/biomedicines12102371.

35. GalaCK, Sandeep, PandeAH, et al. Bispecific domain antibody attenuates airway hyperresponsiveness and pulmonary inflammation in ovalbumin-lipopolysaccharide induced asthma model by inhibiting IL-23 and TNF-α[J]. Pulm Pharmacol Ther, 2025, 88: 102347. DOI: 10.1016/j.pupt.2025.102347.

36. TanS, ChenW, KongG, et al. Peripheral inflammation and neurocognitive impairment: correlations, underlying mechanisms, and therapeutic implications[J]. Front Aging Neurosci, 2023, 15: 1305790. DOI: 10.3389/fnagi.2023.1305790.

37. BohmwaldK, AndradeCA, KalergisAM. Contribution of pro-inflammatory molecules induced by respiratory virus infections to neurological disorders[J]. Pharmaceuticals (Basel), 2021, 14(4): 340. DOI: 10.3390/ph14040340.

38. WangJ, DingN, ChenC, et al. Adropin: a key player in immune cell homeostasis and regulation of inflammation in several diseases[J]. Front Immunol, 2025, 16: 1482308. DOI: 10.3389/fimmu.2025.1482308.

39. BrandhoferM, HoffmannA, BlanchetX, et al. Heterocomplexes between the atypical chemokine MIF and the CXC-motif chemokine CXCL4L1 regulate inflammation and thrombus formation[J]. Cell Mol Life Sci, 2022, 79(10): 512. DOI: 10.1007/s00018-022-04539-0.

40. KuboF, AriestantiDM, OkiS, et al. Loss of the adhesion G-protein coupled receptor ADGRF5 in mice induces airway inflammation and the expression of CCL2 in lung endothelial cells[J]. Respir Res, 2019, 20(1): 11. DOI: 10.1186/s12931-019-0973-6.