Potential of quercitrin in psoriasis intervention: Dual regulation of the oxidative stress-NF-κB axis and gut microbiota homeostasis.

BACKGROUND

Psoriasis, a chronic inflammatory skin disease, imposes a substantial clinical burden with limited long-term treatment efficacy. Quercitrin (QUE), a natural flavonoid possessing anti-inflammatory and antioxidant properties, exhibits therapeutic potential for psoriasis, yet its precise mechanism of action remains to be fully elucidated.

METHODS

To evaluate the effects of QUE, LPS-stimulated HaCaT cells (modeling keratinocyte immune activation) and IMQ-induced psoriatic mice were employed. Skin pathology was assessed by PASI score and histopathological staining. Inflammatory cytokines and oxidative stress markers were measured both in vitro and in vivo using ELISA and commercial kits. NF-κB pathway expression was analyzed by Western blot (in vitro), IHC, and RT-qPCR (in vivo). Molecular docking predicted the binding of QUE to TLR4/MyD88, and 16S rRNA sequencing was used to analyze changes in gut microbiota composition.

RESULTS

QUE effectively inhibited LPS-induced NF-κB activation and oxidative stress in HaCaT cells, leading to reduced release of pro-inflammatory cytokines. In IMQ-induced psoriatic mice, QUE treatment not only alleviated skin lesions and reduced splenomegaly, but also restored the structural integrity of dermal collagen and elastic fibers, thereby improving skin barrier function. Furthermore, QUE suppressed cutaneous NF-κB activation while ameliorating both systemic and local oxidative stress. Molecular docking analysis revealed that QUE directly binds to TLR4 and MyD88. Additionally, QUE restored gut microbiota homeostasis and enhanced intestinal barrier integrity.

CONCLUSIONS

QUE alleviates psoriatic inflammation through synergistic regulation of the NF-κB pathway and gut microbiota homeostasis, exhibiting potential as a multi-target therapeutic agent.