Yiqi Guben capsule alleviates asthmatic airway inflammation through the miR-34a-5p/Notch1 pathway associated with Treg/Th17 immune balance.

Abstract

Objective: This study aimed to explore the mechanisms by which YQGB regulates the balance between regulatory T cells (Tregs) and T helper 17 cells (Th17) and clarify its role in the inflammatory response associated with asthma.

Methods: A total of 60 BALB/c mice were randomly divided into six experimental groups: the control group, the OVA-induced asthma model group (OVA group), the high-dose YQGB treatment group (YQGB(H) group), the medium-dose YQGB (YQGB(M) group), the low-dose YQGB (YQGB(L) group), and the dexamethasone positive control (DEX group). Serum and lung tissue samples were collected to evaluate inflammatory cytokine expression, Treg and Th17 cell proportions, an relevant molecular markers. In vitro, LPS-stimulated MH-S monocultures and MH-S/CD4⁺ T co-culture systems were constructed to mimic pulmonary inflammatory microenvironments, followed by YQGB-containing serum intervention to explore the miR-34a-5p/Notch1 regulatory axis.

Results: Our results showed that YQGB decreased the expression of IL-6, IL-17 A, IL-23, GM-CSF, and Notch1 and promoted the expression of anti-inflammatory cytokines (IL-10 and IL-35) and miR-34a-5p in vivo and in vitro. In mice with OVA-induced asthma, YQGB restored the imbalance in Treg/Th17 and alleviated inflammation and EMT. In LPS-induced MH-S cells, YQGB attenuated inflammatory activation by inhibiting macrophage proliferation and enhancing apoptosis. Additionally, LPS stimulation considerably decreased miR-34a-5p expression, while increasing Notch1 expression.

Conclusion: YQGB alleviates asthmatic airway inflammation, accompanied by altered Treg/Th17 immune balance. Although its therapeutic effects correlate with the miR-34a-5p/Notch1 axis, the causal cascade linking this axis to Treg/Th17 homeostasis remains unproven, indicating its potential as a candidate asthma treatment.