Lurongdabu Decoction alleviates mitochondrial damage and preserves nasal mucosal barrier integrity via the ESR1/PI3K/AKT and EGFR/FAK/SRC signaling pathways.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Lurongdabu Decoction (LRDBD)originated from "Dongyi Shoushi Baoyuan", which is a traditional Chinese medicine palace prescription composed of eight herbs. It has the effects of nourishing the lungs and replenishing essence, protecting the lungs and strengthening the spleen, and clearing the nose and collaterals. However, the mechanism of LRDBD in treating allergic rhinitis (AR) remains unexplored. AIM OF THE STUDY: This study aims to explore whether LRDBD alleviates allergic rhinitisby improving mitochondrial damage to protect the nasal mucosal barrier, and to determine whether its mechanism is related with the estrogen receptor alpha/phosphoinositide 3-kinase/protein kinase B (ESR1/PI3K/AKT) and epidermal growth factor receptor/focal adhesion kinase/steroid receptor coactivator (EGFR/FAK/SRC) signaling pathways. MATERIALS AND METHODS: An AR mouse model was established to evaluate the therapeutic effects of LRDBD. The primary targets and signalling pathways of LRDBD were predicted through network pharmacology analysis. These predictions were further validated using western blotting, immunofluorescence, molecular dynamics (MD) simulations, and molecular docking. In addition, in vivo experiments with mouse models and in vitro studies with human nasal mucosal epithelial cells (HNEPCs) were conducted to examine the pharmacological effects of LRDBD, particularly its influence on mitochondrial function and its role in protecting the nasal mucosal epithelial barrier. CONCLUSIONS: Network pharmacological analysis indicated that LRDBD regulates the activity of the ESR1/PI3K/AKT and EGFR/FAK/SRC signaling pathways. LRDBD alleviates inflammation in mice with AR, reduces the reactive oxygen species (ROS) production in HNEPCs induced by house dust mite (HDM) exposure, decreases cell apoptosis, improves mitochondrial membrane potential, preserves overall mitochondrial function and preserves nasal mucosal barrier.