PMID- 37943488
OWN - NLM
STAT- Publisher
LR  - 20231109
IS  - 1993-0402 (Electronic)
IS  - 1672-0415 (Linking)
DP  - 2023 Nov 9
TI  - Honokiol Prevents Intestinal Barrier Dysfunction in Mice with Severe Acute 
      Pancreatitis and Inhibits JAK/STAT1 Pathway and Acetylation of HMGB1.
LID - 10.1007/s11655-023-3562-y [doi]
AB  - OBJECTIVE: 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: 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: 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- 
      alpha, 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: HON prevented intestinal 
      barrier dysfunction in SAP by inhibiting HMGB1 acetylation and JAK/STAT1 pathway.
CI  - (c) 2023. The Chinese Journal of Integrated Traditional and Western Medicine Press 
      and Springer-Verlag GmbH Germany, part of Springer Nature.
FAU - Li, Jie
AU  - Li J
AD  - Department of General Surgery, Putuo Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200062, China.
FAU - Chen, Ya-Feng
AU  - Chen YF
AD  - Department of General Surgery, Putuo Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200062, China.
FAU - Gao, Lei
AU  - Gao L
AD  - Department of General Surgery, Putuo Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200062, China.
FAU - Li, Yi-Jie
AU  - Li YJ
AD  - Department of General Surgery, Putuo Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200062, China.
FAU - Feng, Dian-Xu
AU  - Feng DX
AD  - Department of General Surgery, Putuo Hospital, Shanghai University of Traditional 
      Chinese Medicine, Shanghai, 200062, China. fdianxu@163.com.
LA  - eng
PT  - Journal Article
DEP - 20231109
PL  - China
TA  - Chin J Integr Med
JT  - Chinese journal of integrative medicine
JID - 101181180
SB  - IM
OTO - NOTNLM
OT  - Janus kinase
OT  - high-mobility group protein B1
OT  - honokiol
OT  - intestinal barrier dysfunction
OT  - severe acute pancreatitis
OT  - signal transducer and activator of transcription 1
EDAT- 2023/11/09 12:42
MHDA- 2023/11/09 12:42
CRDT- 2023/11/09 11:15
PHST- 2023/07/17 00:00 [accepted]
PHST- 2023/11/09 12:42 [medline]
PHST- 2023/11/09 12:42 [pubmed]
PHST- 2023/11/09 11:15 [entrez]
AID - 10.1007/s11655-023-3562-y [pii]
AID - 10.1007/s11655-023-3562-y [doi]
PST - aheadofprint
SO  - Chin J Integr Med. 2023 Nov 9. doi: 10.1007/s11655-023-3562-y.