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

• Published in: Pharmaceutical biology Vol. 59; no. 1; pp. 1214 - 1230
• Main Authors: Huang, Muhua, Wu, Jinfeng, Dong, Jingcheng
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01-01-2021; Taylor & Francis Ltd; Taylor & Francis Group
• Subjects: airway inflammation; Animals; Anti-Asthmatic Agents - pharmacology; Asthma; Asthma - drug therapy; Asthma - immunology; CD4 antigen; CD90 antigen; Cell differentiation; Chinese medicine; Collagen; Dexamethasone; Dexamethasone - pharmacology; Disease Models, Animal; Dose-Response Relationship, Drug; Drugs, Chinese Herbal - administration & dosage; Drugs, Chinese Herbal - pharmacology; Female; GATA-3 protein; Immunity, Innate - drug effects; Interferon regulatory factor 4; Interleukin 13; Interleukin 5; Interleukin 9; Lymphocytes - drug effects; Lymphocytes - immunology; Lymphocytes T; Lymphoid cells; Mice; Mice, Inbred BALB C; neuro-immune communication; Ovalbumin; PU.1 protein; Receptors, Vasoactive Intestinal Peptide, Type II - metabolism; Respiratory Hypersensitivity - drug therapy; Respiratory Hypersensitivity - immunology; Signal transduction; Signal Transduction - drug effects; Thy-1 Antigens - immunology; Transcription factors; type 2 immune response; Vasoactive agents; Vasoactive intestinal peptide; Vasoactive Intestinal Peptide - metabolism; airway inflammation; neuro-immune communication; type 2 immune response; Chinese medicine
• ISSN: 1388-0209; 1744-5116
• DOI: 10.1080/13880209.2021.1970198

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.
We investigated the mechanism underlying the therapeutic effect of M-BYF on allergic asthma.
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.
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 LD
50
value of M-BYF was higher than 90 g/kg.
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.