Traditional wisdom meets modern science: The protective role of sanhuang shu'ai decoction in ulcerative colitis models.

OBJECTIVE

Despite extensive research on ulcerative colitis (UC), the mechanisms behind its pathogenesis remain incompletely elucidated. Sanhuang Shu'ai decoction (SSD) has granted attention for its potential therapeutic influences in inflammatory conditions, yet the protective mechanisms of SSD in UC models are lacking.

METHODS

We investigated the protective effects of SSD extract utilizing two experimental models: lipopolysaccharide (LPS)-induced human colonic organoids and dextran sulfate sodium (DSS)-provoked murine models. In vitro and in vivo validations were conducted to ascertain the protective effects, epithelial barrier (EB) integrity, histological morphology, and inflammatory response following treatment with SSD. Moreover, mechanistic studies were applied to investigate the implication of autophagy modulation and mitophagy activation in the observed protective effects.

RESULTS

Treatment with SSD significantly increased cell viability and EB integrity maintenance in organoids. In DSS-induced UC models, SSD treatment led to considerable improvements in tissue morphology, reduced inflammation, and restored the structural integrity of intestinal epithelial cells, thereby affirming its protective role against UC. Mechanistically, SSD was found to modulate autophagy via PIP4K2C and promote mitophagy through the wogonin-PIP4K2C-PINK1 signaling pathway.

CONCLUSION

SSD effectively alleviates the symptoms of UC by promoting intestinal barrier functionality and decreasing inflammatory responses. The mechanism involves wogonin promoting the interaction between PIP4K2C and PINK1 to form a Wogonin-PIP4K2C-PINK1 trimer complex, start the PINK1/Parkin signaling axis, and then promote mitochondrial autophagy and repair the intestinal EB, thus exerting the effect of treating UC. It provides a new target for UC treatment and promotes the research of Chinese medicine compounds from empirical description to precise regulation.