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 LD 50 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.

Regulatory Peptides in Asthma

“…A role for VIP in the development of asthma has also been demonstrated in studies involving mice lacking the VIP gene that exhibited spontaneous asthma features, such as peribronchial airway inflammation and the production of pro-inflammatory cytokines and AHR, which was partially reduced by administration of exogenous VIP [95]. Therefore, the development of long-acting VIP analogs with strong bronchodilatory effects [76,82] or modulators of the VIP-VPAC2 signaling pathway may provide clinically useful agents for the treatment of asthma [92].…”

“…The VIP immune response is mediated by specific receptors, namely vasoactive intestinal peptide receptor type 1 (VPAC-1) and type 2 (VPAC-2) [87]. VIP is a well-known anti-inflammatory factor that regulates the production of both anti-and pro-inflammatory mediators and the endogenous oxidant/antioxidant balance; reduces IL-1β-induced neutrophil recruitment to the airways; inhibits the activation of macrophages, dendritic cells and microglia [88][89][90]; and promotes a type 2 immune response via the VPAC-2 receptor, which is highly expressed on activated T cells and ILC2s [77,91,92]. Transgenic mice with high constitutive VPAC2 expression in T cells showed immediate-type allergic reaction, in contrast to mice with knockout of the VPAC2 receptor [91][92][93].…”

The Role and Mechanisms of Traditional Chinese Medicine for Airway Inflammation and Remodeling in Asthma: Overview and Progress

“…DC., and Epimedium brevicornu Maxim. A recent study (Huang M. et al, 2021) has reported that the modified BSYQF can alleviate airways inflammation, AHR, mucus hypersecretion, and collagen deposition via a decrease in the expression of the VIP-VPAC2 signaling pathway in the mouse model. BSYQF has more than 16 chemical constituents including acteoside, catalpol, and icariin.…”

Efficacy and safety of modified Bushen Yiqi formulas (MBYF) as an add-on to formoterol and budesonide in the management of COPD: study protocol for a multicentre, double-blind, placebo-controlled, parallel-group, randomized clinical trial: FB-MBYF Trial

“…MBYF consists of five herbs, as shown in Table 1 [ 29 – 31 ]. Furthermore, in vivo and in vitro experiments show that MBYF and its compounds can significantly adjust inflammation and immunology [ 29 , 30 , 32 – 35 ].…”

“…MBYF consists of five herbs, as shown in Table 1 [ 29 – 31 ]. Furthermore, in vivo and in vitro experiments show that MBYF and its compounds can significantly adjust inflammation and immunology [ 29 , 30 , 32 – 35 ]. Icariin in Yinyanghuo has anti-inflammatory effects, upregulates the amount of GRα, and promotes its nuclear translocation in inflammatory cell models and the lung tissue of inflammation animal models [ 36 , 37 ].…”