Study on the Intervention of Hirsutella sinensis Polysaccharides in Atopic Dermatitis via the NF-κB/MAPK and Nrf2/HO-1 Pathways: In Vitro and In Vivo Investigation.

THNOPHARMACOLOGICAL RELEVANCE Hirsutella sinensis is a well-known traditional medicinal fungus used in Chinese and Tibetan folk medicine for treating inflammatory and skin disorders. However, modern scientific evidence supporting its efficacy against atopic dermatitis (AD) remains insufficient, especially for its intracellular polysaccharides (IPS).

Aims

To investigate the anti-AD effects and mechanisms of Hirsutella sinensis intracellular polysaccharides (IPS) and its purified fraction IPS-0, focusing on NF-κB/MAPK, Nrf2/HO-1 pathways and gut-skin axis.

Materials And Methods

Crude IPS was extracted and purified to obtain IPS-0. In vitro assays were performed in TNF-α/IFN-γ-stimulated HaCaT cells. In vivo efficacy was evaluated in DNCB-induced AD mice. Signaling pathways and gut microbiota were analyzed by Western blotting, RT-qPCR and 16S rRNA sequencing.

Results

IPS and IPS-0 markedly alleviated AD symptoms, skin barrier damage and inflammation. They suppressed NF-κB/MAPK activation, reduced pro-inflammatory cytokines, activated Nrf2/HO-1 antioxidant signaling, and restored gut microbiota homeostasis. Pearson analysis verified the gut-skin axis regulation.

Conclusion

IPS exerts anti-AD effects via inhibiting NF-κB/MAPK, activating Nrf2/HO-1 and modulating gut microbiota. These findings validate the traditional use of Hirsutella sinensis and support IPS as a promising natural agent for AD.