Fuzi Lizhong Pill inhibited inflammatory response and promoted colon mucosal healing in dextran sulfate sodium-induced ulcerative colitis mice by down-regulating PI3K/AKT/NF-κB signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE

Fuzi Lizhong Pill (FLP), a traditional Chinese herbal formula, has been historically used for treating gastrointestinal disorders characterized by cold deficiency patterns. Its application in ulcerative colitis (UC) stems from its warming and tonifying properties.

AIM OF THE STUDY

To evaluate the efficacy of FLP in the treatment of UC and investigate its mechanism of action.

MATERIALS AND METHODS

The chemical constituents of FLP were identified using UPLC-Q-Orbitrap HRMS. By establishing a preclinical UC mouse model with DSS and treating with FLP, we evaluated the effect of FLP on UC mice in terms of clinical symptoms, physiological indices, and histopathological examination. The anti-inflammatory and mucosal repair effects of FLP were examined at three levels: cellular, organoid, and animal, using immunohistochemistry, western blotting, RT-PCR, and other techniques.

RESULTS

We characterized the chemical composition of FLP and identified 99 compounds, including alkaloids, coumarins, and flavonoids. In UC mice, FLP alleviated clinical symptoms such as weight loss, blood in stools, and loose stools in UC mice; significantly reduced DAI scores in UC mice; significantly reversed splenomegaly and thymic atrophy caused by DSS; improved hemorrhage and inflammation-related hematological indices. In vitro and ex vivo studies showed that FLP inhibited the expression of TNF-α and IL-6, promoted the expression of the tight junction proteins ZO-1, Occludin, and Claudin 1, and promoted the proliferation of colonic epithelial cells in vivo. FLP also inhibited the transcription levels of PI3K, Akt, and NF-κB genes, as well as the expression or phosphorylation levels of related proteins in vitro and in vivo.

CONCLUSION

FLP may play a role in the treatment of UC by inhibiting the inflammatory response and repairing the colonic mucosal barrier by downregulating the PI3K/Akt/NF-κB signaling pathway.