Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 28, 2021; 27(44): 7669-7686
Published online Nov 28, 2021. doi: 10.3748/wjg.v27.i44.7669
Calycosin attenuates severe acute pancreatitis-associated acute lung injury by curtailing high mobility group box 1 - induced inflammation
Chang-Ju Zhu, Wan-Guang Yang, De-Jian Li, Yao-Dong Song, San-Yang Chen, Qiao-Fang Wang, Yan-Na Liu, Yan Zhang, Bo Cheng, Zhong-Wei Wu, Zong-Chao Cui
Chang-Ju Zhu, Wan-Guang Yang, De-Jian Li, Yao-Dong Song, San-Yang Chen, Qiao-Fang Wang, Yan-Na Liu, Yan Zhang, Bo Cheng, Zhong-Wei Wu, Zong-Chao Cui, Henan Medical Key Laboratory of Emergency and Trauma Research, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Chang-Ju Zhu, Wan-Guang Yang, De-Jian Li, San-Yang Chen, Qiao-Fang Wang, Yan-Na Liu, Key Laboratory of Hepatobiliary and Pancreatic Surgery and Digestive Organ Transplantation of Henan Province, The First Affiliated Hospital of Zhengzhou University, Zhengzhou 450052, Henan Province, China
Author contributions: Zhu CJ and Yang WG designed the experiments; Li DJ, Chen SY, Wang QF and Liu YN performed the experiments; Wu ZW, Cui ZC, Zhang Y and Cheng B performed data analysis; Li DJ drafted and revised the manuscript; all authors wrote, read and approved the final manuscript.
Supported by the Key Research Projects of Henan Higher Education Institutions, No. 20A320064.
Institutional review board statement: This study was reviewed and approved by the Ethics Committee of The First Affiliated Hospital of Zhengzhou University.
Institutional animal care and use committee statement: All animal experiments were conducted in accordance with relevant guidelines and regulations and approved by the Animal Ethics Committee of The National Drug Clinical Trial Institution of The First Affiliated Hospital of Zhengzhou University (Ethic Review Number: 2019-KY-140).
Conflict-of-interest statement: The authors have no conflicts of interest to declare.
Data sharing statement: No additional data are available.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Chang-Ju Zhu, PhD, Academic Fellow, Chief Doctor, Henan Medical Key Laboratory of Emergency and Trauma Research, The First Affiliated Hospital of Zhengzhou University, No. 1 Eastern Jianshe Road, Zhengzhou 450052, Henan Province, China. zhuchangju98@163.com
Received: May 17, 2021
Peer-review started: May 17, 2021
First decision: June 26, 2021
Revised: July 9, 2021
Accepted: September 10, 2021
Article in press: September 10, 2021
Published online: November 28, 2021
Processing time: 192 Days and 1.4 Hours
Abstract
BACKGROUND

Acute lung injury (ALI) is a common and life-threatening complication of severe acute pancreatitis (SAP). There are currently limited effective treatment options for SAP and associated ALI. Calycosin (Cal), a bioactive constituent extracted from the medicinal herb Radix Astragali exhibits potent anti-inflammatory properties, but its effect on SAP and associated ALI has yet to be determined.

AIM

To identify the roles of Cal in SAP-ALI and the underlying mechanism.

METHODS

SAP was induced via two intraperitoneal injections of L-arg (4 g/kg) and Cal (25 or 50 mg/kg) were injected 1 h prior to the first L-arg challenge. Mice were sacrificed 72 h after the induction of SAP and associated ALI was examined histologically and biochemically. An in vitro model of lipopolysaccharide (LPS)-induced ALI was established using A549 cells. Immunofluorescence analysis and western blot were evaluated in cells. Molecular docking analyses were conducted to examine the interaction of Cal with HMGB1.

RESULTS

Cal treatment substantially reduced the serum amylase levels and alleviated histopathological injury associated with SAP and ALI. Neutrophil infiltration and lung tissue levels of neutrophil mediator myeloperoxidase were reduced in line with protective effects of Cal against ALI in SAP. Cal treatment also attenuated the serum levels and mRNA expression of pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, IL-1β, HMGB1 and chemokine (CXC motif) ligand 1 in lung tissue. Immunofluorescence and western blot analyses showed that Cal treatment markedly suppressed the expression of HMGB1 and phosphorylated nuclear factor-kappa B (NF-κB) p65 in lung tissues and an in vitro model of LPS-induced ALI in A549 cells suggesting a role for HGMB1 in the pathogenesis of ALI. Furthermore, molecular docking analysis provided evidence for the direct interaction of Cal with HGMB1.

CONCLUSION

Cal protects mice against L-arg-induced SAP and associated ALI by attenuating local and systemic neutrophil infiltration and inflammatory response via inhibition of HGMB1 and the NF-κB signaling pathway.

Keywords: Severe acute pancreatitis; Acute lung injury; Calycosin; Mouse model; High-mobility group box 1; Nuclear factor-kappa B

Core Tip: In this study, we showed that Calycosin protects mice against L-arginine-induced severe acute pancreatitis (SAP) and associated acute lung injury (ALI) by attenuating local and systemic inflammatory response via inhibition of high mobility group box 1 (HGMB1) and the nuclear factor-kappa B signaling pathway. Suppression of HMGB1 expression is a potential target for the treatment of SAP-ALI.