Pharm Biol. 2020 Dec ;58(1):898-904. PMID: 32893702
Sesamin attenuates intestinal injury in sepsis via the HMGB1/TLR4/IL-33 signalling pathway.
CONTEXT: Sepsis is currently one of the leading causes of death in intensive care units (ICUs). Sesamin was previously reported to inhibit inflammation. However, no studies have revealed the impact of sesamin on sepsis.OBJECTIVE: We studied the mechanism underlying the effect of sesamin on the pathophysiology of sepsis through the HMGB1/TLR4/IL-33 signalling pathway.MATERIALS AND METHODS: Fifty male BALB/c mice ( = 10 per group) were used to establish a caecal ligation and puncture (CLP) mouse model, and given daily injections of sesamin at a low, middle, or high concentration (25, 50, or 100 μM) during the seven-day study period; survival curves were generated by the Kaplan-Meier method. H&E staining and TUNEL staining were performed to assess changes in intestinal morphology intestinal damage in the mouse intestinal epithelium. Molecules related to the HMGB1/TLR4/IL-33 pathway were assessed by RT-qPCR and Western blotting.RESULTS: We found mice in the sepsis group survived for only 4 days, while those treated with sesamin survived for 6-7 days. In addition, sesamin significantly relieved the increase in the levels of MPO (21%, 33.3%), MDA (40.5% and 31.6%), DAO (1.24-fold and 2.31-fold), and pro-inflammatory cytokines such as TNF-α (75% and 79%) and IL-6 (1-fold and 1.67-fold) 24 and 48 h after sepsis induction and downregulated the expression of HMGB1, TLR4, and IL-33 while upregulating the expression of ZO-1 and occludin.DISCUSSION AND CONCLUSIONS: Sesamin improved the 7-day survival rate of septic mice, suppressed the inflammatory response in sepsis through the HMGB-1/TLR4/IL-33 signalling pathway, and further alleviated intestinal injury.