Modified Pulsatilla decoction alleviates DSS-induced colitis in mice by modulating gut microbiota and promoting IL-10 and IL-22 expression.

BACKGROUND: Pulsatilla decoction (PD), a traditional Chinese formulation composed of Pulsatillae Radix (Pulsatilla chinensis), Coptidis Rhizoma (Coptis chinensis), Phellodendri Cortex (Phellodendron chinense), and Fraxini Cortex (Fraxinus chinensis), has long been used to treat chronic colitis. Previous studies demonstrated its antidiarrheal effects and proposed underlying mechanisms. Building on these findings, this study aimed to optimize PD by refining its bioactive components to develop a more effective formulation. METHODS: An in vitro assay was conducted using two strains of lactic acid bacteria to assess the impact of PD components on their growth. The growth and lactic acid production of these bacteria were assessed in response to the polysaccharides and small molecules present in PD. A modified PD (mPD) was created by removing components with adverse effects on the beneficial bacteria. The efficacy of mPD was evaluated in a dextran sulfate sodium (DSS)-induced colitis mouse model, with assessments including the disease activity index, intestinal inflammation, cytokine levels, macrophage infiltration, microbiota composition, and short-chain fatty acid (SCFA) levels. RESULTS: Methanol extracts from Coptidis Rhizoma (CR) and Phellodendri Cortex (PC) were found to inhibit lactic acid bacteria growth significantly versus other extracts. The mPD showed significantly improved efficacy compared to the original PD. It demonstrated superior anti-inflammatory effects, promoted tissue repair, increased levels of anti-inflammatory cytokines such as IL-10 and IL-22, and enhanced SCFA production. Furthermore, mPD favorably altered gut microbiota by reducing the Akkermansiaceae-to-Lachnospiraceae ratio, thereby effectively alleviating colitis symptoms. CONCLUSION: After removing components that suppressed Lactobacillus proliferation, mPD exhibited greater efficacy against DSS-induced colitis. This improvement is likely associated with strengthened modulation of gut microbiota and inflammatory pathways. These results support microbiota-guided herbal optimization as a rational strategy for colitis management.