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

Abstract

Purpose: 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.

Methods: 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.

Results: 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.

Conclusion: 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.