Angelicin attenuates sepsis-associated splenic injury by targeting NF-κB/JAK2/STAT3 and PI3K/Akt pathways to inhibit inflammation and apoptosis.

Abstract

Sepsis represents a clinical syndrome characterized by maladaptive host immune dysregulation in response to infection, leading to potentially fatal multiorgan dysfunction. As the largest secondary lymphoid organ in mammals, spleen tissue plays a fundamental role in immune defense. Angelicin (ANG), the main active ingredient in the traditional Chinese medicine Psoralea corylifolia Linn., possesses biological activities such as anti-inflammation and anti-apoptosis. This study established a mouse sepsis-associated splenic injury model using cecal ligation and puncture (CLP) to systematically analyze the protective effects of ANG and its underlying mechanisms. Additionally, the J774A.1 cell model stimulated with lipopolysaccharide (LPS) was used to further validate the pathway regulation phenomena observed in vivo. The results showed that ANG treatment significantly attenuated sepsis-associated splenic injury in mice. qPCR results showed that ANG downregulated pro-inflammatory and upregulated anti-inflammatory cytokine transcripts. TUNEL results showed that ANG treatment inhibited the ratio of TUNEL-positive cells. Further studies demonstrated that ANG suppressed inflammatory responses by inhibiting the NF-κB and JAK2/STAT3 pathways, and alleviate apoptosis by activating the PI3K/Akt pathway. Notably, the suppressive effect of ANG on JAK2/STAT3 pathway was dependent on the inhibition of the NF-κB pathway.