Modified BuShenYiQi formula alleviates experimental allergic asthma in mice by negative regulation of type 2 innate lymphoid cells and CD4⁺ type 9 helper T cells and the VIP–VPAC2 signalling pathway

Abstract

Context

Modified BuShenYiQi formula (M-BYF) is derived from BuShenYiQi formula, used for the treatment of allergic asthma. The exact effect and mechanism of M-BYF on the improvement of asthma remain unclear.

Objective

We investigated the mechanism underlying the therapeutic effect of M-BYF on allergic asthma.

Materials and methods

The asthma model was established in female BALB/c mice that were sensitized and challenged with ovalbumin (OVA). Mice in the treated groups were orally treated once a day with M-BYF (7, 14 and 28 g/kg/d) or dexamethasone before OVA challenge. Control and Model group received saline. Pathophysiological abnormalities and percentages of lung type 2 innate lymphoid cells (ILC2s) and Th9 cells were measured. Expression levels of type 2 cytokines and transcription factors required for these cells function and differentiation were analysed. Expression of vasoactive intestinal polypeptide (VIP)–VPAC2 signalling pathway-related proteins, and percentages of VIP expressing (VIP⁺) cells and VPAC2, CD90 co-expressing (VPAC2⁺CD90⁺) cells were detected.

Results

M-BYF alleviated airway hyperresponsiveness, inflammation, mucus hypersecretion and collagen deposition in asthmatic mice. M-BYF down-regulated percentages of ILC2s and Th9 cells with lower expression of GATA3, PU.1 and IRF4, reduced IL-5, IL-13, IL-9 and VIP production. The decrease in the expression of VIP–VPAC2 signalling pathway and percentages of VIP⁺ cells, VPAC2⁺CD90⁺ cells were observed after M-BYF treatment. The LD₅₀ value of M-BYF was higher than 90 g/kg.

Discussion and conclusions

M-BYF alleviated experimental asthma by negatively regulating ILC2s and Th9 cells and the VIP–VPAC2 signalling pathway. These findings provide the theoretical basis for future research of M-BYF in asthma patient population.

Keywords:

• Chinese medicine
• type 2 immune response
• neuro-immune communication
• airway inflammation

Acknowledgements

The authors thank members of the integrative medicine laboratory of Huashan Hospital, Fudan University for technical assistance.

Disclosure statement

The authors report no declarations of interest.

Additional information

Funding

This work was supported by the National Natural Science Foundation of China [No. 81774074] and 3 Years to Accelerate the Development of Chinese Medicine in Shanghai, China [No. ZY (2018-2020)-FWTX-4016].