Honokiol Prevents Intestinal Barrier Dysfunction in Mice with Severe Acute Pancreatitis and Inhibits the JAK/STAT1 Pathway and Acetylation of HMGB1

Objective: To investigate the effect of honokiol (HON) and the role of HMGB1 on the pathogenesis of severe acute pancreatitis (SAP) in a mouse model. Methods : Thirty mice were randomly divided into 5 groups: control (CON), SAP, SAP and normal saline (SAP+NS), SAP and ethyl pyruvate (SAP+EP), or SAP+HON. Samples of the pancreas, intestine, and blood were collected 12 h after model induction for examination of pathologic changes, alterations of immune function, and abnormalities of HMGB1-related pathways using microscopy, ELISA, and western blotting. Results : Mice with SAP had inflammatory injury of the pancreas, bleeding of intestinal tissues, and cells with disrupted histology, but mice in the SAP+HON group had significantly fewer pathological changes. Mice with SAP also had significant increases in the serum levels of amylase (AMY), lipase, HMGB1, tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), diamine oxidase (DAO), endotoxin 1 (ET-1), and procalcitonin (PCT), but mice in the SAP+HON group did not have these abnormalities. Studies of Caco-2 cells indicated that lipopolysaccharide (LPS) increased the levels of occludin and claudin-1, increased tight junction-permeability, and decreased the level of junctional adhesion molecule C (JAM-C), but HON treatment blocked these effects. Studies of macrophages indicated that LPS led to low nuclear levels of HMGB1, but HON treatment increased the nuclear level of HMGB1. HON treatment also inhibited the expression of JAK1, JAK2, and STAT1 and increased the acetylation of HMGB1. Conclusion : HON prevents intestinal barrier dysfunction in SAP by inhibiting HMGB1 acetylation and the JAK/STAT1 pathway.