Exploring Cistanche's therapeutic potential and molecular mechanisms in asthma treatment

Asthma, a prevalent chronic respiratory disease, is characterized by airway inflammation and hyperresponsiveness, significantly impacting global health. Current treatments, including corticosteroids, face limitations due to variable patient responses and side effects. This study explores the therapeutic potential of Cistanche, a traditional Chinese medicinal herb, in an asthmatic mouse model induced by house dust mites (HDM). We employed a multidisciplinary approach, including transcriptomics, mass spectrometry, Weighted Gene Co-expression Network Analysis (WGCNA), and experimental validation in animal and cellular models. Our findings demonstrate that Cistanche significantly attenuates airway hyperresponsiveness, cellular infiltration, and mucus hypersecretion in asthmatic mice. Transcriptomic analysis identified 643 differentially expressed genes (DEGs), with Cistanche treatment disrupting pathways associated with IL-4, IL-5, and eosinophils. Gene Set Enrichment Analysis (GSEA) revealed Cistanche's involvement in glucocorticoid processes, suggesting its potential as an alternative or complementary therapy to conventional glucocorticoids. Liquid Chromatography-High Resolution Mass Spectrometry (LCHRMS) analysis identified Pinoresinol 4-O-Beta-D-Glucopyranoside (PG) as a key active component of Cistanche, with targets predominantly associated with the PI3K-AKT pathway. WGCNA analysis of an asthma dataset identified the "skyblue" module as highly associated with asthma, with inducible nitric oxide synthase (iNOS) emerging as a core gene. Molecular docking confirmed a strong binding affinity between PG and iNOS, with Cistanche treatment down-regulating iNOS expression, suggesting a potential mechanism for its anti-inflammatory effects. In conclusion, Cistanche exhibits therapeutic effects in asthma by modulating immune responses and targeting key asthma-related genes and proteins. Our study provides novel insights into the treatment of asthma with natural products and highlights the potential of Cistanche as an alternative or complementary therapeutic agent. Further research is warranted to validate these findings and explore the integration of Cistanche into clinical asthma management.