Epimedii Folium and Ligustri Lucidi Fructus combination restores HPA axis and glucocorticoid synthesis in rat asthma model

Asthma is a chronic inflammatory airway disease, and a significant challenge in clinical practice is glucocorticoid (GC) resistance or insufficient endogenous GC synthesis, which limits therapeutic options. The hypothalamic-pituitary-adrenal (HPA) axis is crucial for regulating GC production, and its dysfunction can exacerbate asthma pathology. This study investigates traditional Chinese medicinal herbs, Epimedii Folium and Ligustri Lucidi Fructus, for their potential to address this specific gap by modulating the HPA axis and peripheral GC metabolism.

Researchers established a complex asthma model in male SD rats by ovalbumin (OVA) sensitization and challenge, combined with intraperitoneal metyrapone (Met) administration to specifically suppress the HPA axis and endogenous GC synthesis. Rats were assigned to six groups: normal, Met, asthma+Met, Epimedii Folium, Ligustri Lucidi Fructus, and Epimedii Folium+Ligustri Lucidi Fructus. Following a one-week drug treatment via gavage (doses not specified), serum levels of CRH, ACTH, CORT, and COR were measured. Urinary endogenous GC metabolism was assessed via targeted metabolomics. Expression of HSD11B1, HSD11B2, CYP11B1, and SF1 in lung and adrenal gland was evaluated by immunohistochemical staining, and related liver proteins by Western blot.

In the GC synthesis-restricted asthma model, both Epimedii Folium and Ligustri Lucidi Fructus individually, and especially in combination, significantly improved markers of HPA axis function and GC metabolism.

The combination of Epimedii Folium and Ligustri Lucidi Fructus elevated serum concentrations of CRH, ACTH, CORT, and COR in model rats, indicating a restoration of HPA axis activity. The herbal treatments partially reversed abnormalities observed in the urinary GC metabolic profile. Furthermore, they upregulated the expression of key synthetic and metabolic enzymes, including HSD11B1, HSD11B2, CYP11B1, and SF1, across the lung, liver, and adrenal gland tissues. These findings suggest a multi-faceted regulatory effect on both the HPA axis and peripheral GC synthesis/metabolism, synergistically ameliorating endogenous GC dysregulation in the asthma model.