Objective:

2

To investigate the effect of honokiol (HON) and the role of high-mobility group protein B1 (HMGB1) on the pathogenesis of severe acute pancreatitis (SAP).

Methods:

2

Thirty mice were numbered according to weight

and randomly divided into 5 groups using a random number table

including control

SAP

SAP and normal saline (SAP+NS)

SAP and ethyl pyruvate (SAP+EP)

or SAP+HON groups

6 mice in each group. Samples of pancreas

intestine

and blood were collected 12 h after SAP model induction for examination of pathologic changes

immune function alterations by enzyme linked immunosorbent assay (ELISA)

and Western blot.

In vitro

experiments

macrophages were divided into 5 groups

the control

lipopolysaccharide (LPS)

LPS+DMSO (DMSO)

LPS+anti-HMGB1 monoclonal antibody (mAb)

and LPS+ HON groups. The tight connection level was determined by transmission electron microscopy and fluorescein isothiocyanate-labeled. The location and acetylation of HMGB1 were measured by Western blot. Finally

pyridone 6 and silencing signal transducer and activator of the transcription 1 (siSTAT1) combined with honokiol were added to determine whether the Janus kinase (JAK)/ STAT1 participated in the regulation of honokiol on HMGB1. The protein expression levels of HMGB1

JAK

and STAT1 were detected using Western blot.

Results:

2

Mice with SAP had inflammatory injury in the pancreas

bleeding of intestinal tissues

and cells with disrupted histology. Mice in the SAP+HON group had significantly fewer pathological changes. Mice with SAP also had significant increases in the serum levels of amylase

lipase

HMGB1

tumor necrosis factor-α

interleukin-6

diamine oxidase

endotoxin-1

and procalcitonin. Mice in the SAP+HON group did not show these abnormalities (

P

<

0.01). Studies of Caco-2 cells indicated that LPS increased the levels of occludin and claudin-1 as well as tight junction permeability

decreased the levels of junctional adhesion molecule C

and elevated intercellular permeability (

P

<

0.01). HON treatment blocked these effects. Studies of macrophages indicated that LPS led to low nuclear levels of HMGB1

however

HON treatment increased the nuclear level of HMGB1 (

P

<

0.01). HON treatment also inhibited the expressions of JAK1

JAK2

and STAT1 (

P

<

0.01) and increased the acetylation of HMGB1 (

P

<

0.05).

Conclusion:

2

HON prevented intestinal barrier dysfunction in SAP by inhibiting HMGB1 acetylation and JAK/STAT1 pathway.