Radix Sanguisorbae Improves Intestinal Barrier in Septic Rats via HIF-1 α/HO-1/Fe²⁺ Axis

Area of Science:

• Pharmacology and Toxicology
• Gastroenterology
• Critical Care Medicine

Background:

• Sepsis leads to severe intestinal barrier dysfunction, multi-organ injury, and increased mortality.
• Traditional Chinese Medicine, such as Radix Sanguisorbae (RS, Diyu), is explored for its therapeutic potential in critical conditions.
• Understanding the mechanisms by which RS mitigates sepsis-induced damage is crucial for developing novel treatments.

Purpose of the Study:

• To evaluate the efficacy of Radix Sanguisorbae (RS) in restoring intestinal barrier function during sepsis.
• To investigate the underlying mechanisms of RS action, including its effects on ferroptosis and inflammatory pathways.
• To assess the impact of RS on survival rates and organ function in a sepsis model.

Main Methods:

• A cecal ligation and puncture (CLP)-induced septic rat model and lipopolysaccharide (LPS)-challenged IEC-6 cell model were utilized.
• RS was administered to rats before and after CLP induction; various physiological and biochemical parameters were measured.
• In vitro studies assessed RS effects on cell viability, tight junction proteins (ZO-1), and ferroptosis markers.

Main Results:

• RS treatment significantly improved intestinal barrier function and reduced intestinal inflammation in septic rats.
• RS administration increased the 72-h survival rate to 43.75% and prolonged survival time to 56 hours.
• RS inhibited lipid peroxidation and ferroptosis in vivo and in vitro, with network pharmacology suggesting involvement of the HIF-1α signaling pathway.

Conclusions:

• Radix Sanguisorbae (RS) demonstrates significant therapeutic potential in ameliorating sepsis-induced intestinal injury.
• RS improves intestinal barrier function and survival by inhibiting ferroptosis, partly through the HIF-1α/heme oxygenase-1/Fe²⁺ axis.
• These findings support the use of RS as a potential adjunct therapy for sepsis management.