Dachengqi Decoction Attenuates Inflammatory Response via Inhibiting HMGB1 Mediated NF-κB and P38 MAPK Signaling Pathways in Severe Acute Pancreatitis.
OBJECTIVE
Severe acute pancreatitis (SAP) is a sudden inflammation of the pancreas. The traditional Chinese medicine formula Dachengqi decoction (DCQD) is proven to be beneficial in the comprehensive treatment for pancreatitis patients in clinical practice. However, the molecular mechanism of DCQD on SAP remains unclear. High mobility group box 1(HMGB1) that functions as a damage-associated molecular pattern molecule (DAMP) has attracted much interest.


METHODS
In this study, we used lipopolysaccharide (LPS) and cerulein to induce severe acute pancreatitis in C57BL/6 mice with subsequent administration with low, medium and high dose (2.3 g/kg, 7 g/kg and 21 g/kg, respectively) of DCQD.


RESULTS
DCQD treatment improved the pathological score and decreased serum amylase and lipase in a dose-dependent manner. In addition, it suppressed the immune cell-induced secretion of HMGB1 and its translocation from the nucleus to the cytoplasm, thus repressing the expression of IL-6 and TNF-α. Further, pretreatment with DCQD decreased responses of TLRs, and suppressed the activation of NF-κB and p38 MAPK pathway.


CONCLUSIONS
Decreasing the secretion of HMGB1 could reduce pro-inflammatory cytokines, which may help cutting down the risks of development from localized pathological changes to a systemic inflammatory response syndrome and even lead to multiple organ failure.
Zhuoan
Z
Chen
Yafeng
Y
Chen
Liyun
L
Pan
Hongchang
H
Li
Jiamin
J
Tu
Cheng
C
Liu
Xiuqin
X
Dai
Xiaofen
X
Zhang
Guifang
G
Sun
Dianxu
D
Feng
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D004797:Enzyme-Linked Immunosorbent Assay; D024243:HMGB1 Protein / Q000378:metabolism*; D015850:Interleukin-6 / Q000097:blood; D008049:Lipase / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008856:Microscopy, Fluorescence; D016328:NF-kappa B / Q000378:metabolism*; D010179:Pancreas / Q000378:metabolism / Q000473:pathology; D010195:Pancreatitis / Q000378:metabolism / Q000473:pathology; D010936:Plant Extracts / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*; D051197:Toll-Like Receptor 4 / Q000378:metabolism; D051217:Toll-Like Receptor 9 / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D024243:HMGB1 Protein; D015850:Interleukin-6; D016328:NF-kappa B; D010936:Plant Extracts; C493487:Tlr4 protein, mouse; C495370:Tlr9 protein, mouse; D051197:Toll-Like Receptor 4; D051217:Toll-Like Receptor 9; D014409:Tumor Necrosis Factor-alpha; C477169:dachengqi decoction; D048051:p38 Mitogen-Activated Protein Kinases; D008049:Lipase; D000681:Amylases