Ginsenoside Rg2 upregulates expression of Lilrb4 and inhibits the NF-κB signaling pathway to alleviate hemorrhagic shock/reperfusion-induced intestinal injury.

Hemorrhagic shock/reperfusion (HS/R) injury is associated with high global mortality, and intestinal injury plays a pivotal role in driving systemic complications. This study examined the therapeutic potential of Ginsenoside Rg2 (G-Rg2) in mitigating HS/R intestinal injury and elucidated its relationship involving leukocyte immunoglobulin-like receptor B4 (Lilrb4). Using an established rat HS/R model and hypoxia/reoxygenation (H/R) IEC-6 cells, we evaluated the effects of G-Rg2 on intestinal barrier integrity, inflammatory responses, oxidative stress, and apoptosis. The results indicated that G-Rg2 treatment significantly alleviates intestinal mucosal damage, inhibits epithelial apoptosis, and restores tight junction proteins (Occludin, ZO-1). In vitro experiments revealed that G-Rg2 enhances cell viability, suppresses reactive oxygen species (ROS) overproduction, and reduces pro-inflammatory cytokines (TNF-α, IL-6, and IL-1β). Mechanistically, G-Rg2 upregulated Lilrb4 expression, and supressed NF-κB pathway activation. Collectively, these findings suggested that G-Rg2 alleviates HS/R-induced intestinal injury by the upregulation of Lilrb4 and the inhibition of the NF-κB pathway.