Qi-Huang decoction alleviates DSS-induced colitis with Candida albicans dysbiosis by enhancing innate immune response through Dectin-1-associated signaling

Abstract

Background

Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract. Candida albicans, a common commensal fungus in the human gut, has been increasingly implicated in UC pathogenesis. Qi-Huang decoction (QHD), a traditional Chinese herbal formula known for its spleen-invigorating and purgative properties, is commonly used to restore gastrointestinal function.

Purpose

This study investigates the therapeutic potential of QHD in treating colitis exacerbated by C. albicans and explores the underlying mechanisms of action.

Methods

A mouse model of colitis was induced using dextran sulfate sodium combined with gavage of C. albicans. Following QHD treatment, colitis severity was evaluated by measuring survival rate, body weight, disease activity index, colon length, and fungal burden, and through histopathological analysis using hematoxylin-eosin staining. The expression of proinflammatory genes IL-1β and TNF-α was quantified, alongside protein levels of key molecules involved in Dectin-1 signaling, including Syk, CARD-9, NLRP-3, Raf-1, and NF-κB. Barrier integrity markers, such as Occludin and Claudin-1, were also examined. To further elucidate QHD's mechanisms, Dectin-1 was inhibited using laminarin. In vitro experiments assessed QHD's antifungal activity against three Candida strains through microdilution, spot assays, and time-kill tests. RAW 264.7 macrophages were employed to study the exposure of fungal cell wall β-glucan and subsequent phagocytosis. Molecular docking simulations predicted interactions between QHD's active compounds and the Dectin-1 receptor.

Results

QHD significantly mitigated colitis severity and reduced fungal burden in vivo. QHD enhanced β-glucan exposure on the fungal cell wall, thereby stimulating phagocytosis by RAW264.7 macrophages. QHD effectively activated Dectin-1-mediated signaling pathways and increased proinflammatory levels in RAW 264.7 cells. In colitis mice, QHD treatment markedly reduced inflammation and Dectin-1 signaling following fungal clearance. However, Dectin-1 inhibition with LAM neutralized QHD's therapeutic effects, highlighting the pathway's importance in mediating QHD's efficacy. Interestingly, QHD alone elevated Dectin-1, NF-κB, TGF-β, and IL-10 levels, whereas reduced IL-1β and TNF-α expression, suggesting a dual modulatory role in inflammation. Molecular docking confirmed a potential direct interaction between QHD's bioactive components and the Dectin-1 receptor.

Conclusion

QHD demonstrates promising therapeutic potential for managing Candida colitis by modulating immune responses and targeting Dectin-1 signaling pathways in clinical settings.