Abstract
In bronchial asthma, M2 macrophage polarization and PI3K/Akt/mTOR pathway activation are critically implicated in airway inflammation and remodeling. This study employed an OVA-induced asthmatic mouse model to evaluate the therapeutic effect of Epimedin C, a major flavonoid from Herba Epimedii with reported anti-inflammatory and immunoregulatory effects. Pulmonary function tests, histological staining, ELISA, RT-qPCR, and western blotting were utilized to assess airway responsiveness, inflammation, and remodeling. The mechanisms involving the PI3K/Akt/mTOR pathway and macrophage polarization were further investigated via flow cytometry and immunofluorescence. Results showed that Epimedin C significantly improved lung function and alleviated pathological changes. These therapeutic effects were accompanied by suppression of PI3K/Akt/mTOR phosphorylation and inhibition of M2 polarization. Further mechanistic investigation confirmed that M2 polarization was dependent on PI3K/Akt/mTOR activation. Inhibiting this pathway can reverse M2 hyperpolarization and reduce pro-inflammatory mediator production. In conclusion, Epimedin C may alleviate asthma by suppressing M2 macrophage polarization through inhibition of the PI3K/Akt/mTOR pathway. These findings may offer a novel understanding of Epimedin C treatment and furnish evidence for an alternative therapeutic approach to asthma.
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The datasets during and/or analyzed during the current study are available from the corresponding author upon reasonable request.
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Funding
This study was supported by the National Nature Science Foundation of China grant (No. 82405322) and the Natural Science Foundation of Shandong Province Youth Program of China (No. ZR2023QH089).
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ZZ, YC, and YW conceived and designed the review. ZZ, SC, and ZQ wrote the manuscript and prepared the figures. TL, YW, and YC performed the literature search. YC, ZZ, CH, and YW revised it critically for important intellectual content. All authors have read and approved the final manuscript. All authors are responsible for all aspects of the work and approve the submission in its current form. Data authentication is not applicable.
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The animal studies were approved by the ethics committee on animal care of Shandong Provincial Hospital & Shandong First Medical University, Jinan, China (2024 − 553). All experiments meet the requirements of the ARRIVE guidelines. All animal studies were carried out in accordance with the NIH guidelines in 2011 for the care and use of laboratory animals.
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Zhang, Z., Cao, S., Qin, Z. et al. Epimedin C attenuates airway inflammation and remodeling in Asthma by intervening M2 macrophage polarization via modulating the PI3K/Akt/mTOR signaling pathway. Sci Rep (2026). https://doi.org/10.1038/s41598-026-42160-4
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DOI: https://doi.org/10.1038/s41598-026-42160-4
