Large Chengqi Decoction Improves Sepsis-Related Intestinal Damage by Inhibiting Inflammatory Response Through the HMGB1-TLR4 Signaling Pathway

This study aimed to evaluate the therapeutic efficacy of Large Chengqi Decoction(LCD) in attenuating sepsis-related intestinal injury by targeting the HMGB1-TLR4 signaling pathway.

Seventy-five Sprague-Dawley (SD) rats were utilized to establish a septic intestinal injury model, randomized into sham operation, model control, and three treatment groups (LCD0.1, LCD1, LCD10). HMGB1, TLR4, IL-6, and MCP-1 levels in intestinal tissues were assessed via ELISA and Western blotting. Histopathological changes were examined using HE staining of ileum sections.

Compared to the sham group, the model group showed significant elevation of inflammatory markers, confirming successful model establishment. In the LCD1 group, HMGB1 levels were notably higher at 3 and 5 days, accompanied by consistent TLR4 downregulation. IL-6 levels were significantly reduced at 3 days, and MCP-1 levels were lower compared to the sham group. LCD10 group exhibited decreased HMGB1 levels at 5 days and reduced IL-6 levels at 3 days. Immunohistochemical analysis at 3 days post-modeling indicated that LCD1 group expressions of HMGB1, TLR4, NF-κB, and MCP-1 resembled the sham group and significantly differed from the model group. Both LCD1 and LCD10 groups showed improved ileal damage and reduced edema compared to the model group.

LCD effectively mitigates inflammatory responses in septic rats by modulating the HMGB1-TLR4/NF-κB pathway, thereby promoting intestinal repair. Concentrations of 1g/mL and 10g/mL present promising therapeutic strategies for sepsis-related intestinal injury, highlighting the potential of traditional Chinese medicine in sepsis treatment research.