Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Dec 6, 2021; 9(34): 10451-10463
Published online Dec 6, 2021. doi: 10.12998/wjcc.v9.i34.10451
Magnolol protects against acute gastrointestinal injury in sepsis by down-regulating regulated on activation, normal T-cell expressed and secreted
Shi-Hao Mao, Dan-Dan Feng, Xi Wang, Yi-Hui Zhi, Shu Lei, Xi Xing, Rong-Lin Jiang, Jian-Nong Wu
Shi-Hao Mao, Dan-Dan Feng, Yi-Hui Zhi, Shu Lei, Xi Xing, Rong-Lin Jiang, Jian-Nong Wu, Department of Intensive Care Unit, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, Zhejiang Province, China
Xi Wang, Key Laboratory of Digestive Pathophysiology of Zhejiang Province, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China
Author contributions: Mao SH, Wu JN, Feng DD and Jiang RL designed and coordinated the research study; Mao SH, Wu JN, Feng DD and Wang X performed the research; Lei S, Zhi YH and Xing X interpreted the data; Mao SH, Feng DD and Wang X analyzed the data and wrote the manuscript; all authors have read and approved the final manuscript.
Supported by Basic Public Welfare Research Foundation of Zhejiang Province, China, No. GD21H290001; and Traditional Chinese Medicine Science and Technology Project Foundation of Zhejiang Province, China, No. 2020ZB072.
Institutional animal care and use committee statement: All animal experiments conformed to the internationally accepted principles for the care and use of laboratory animals (licence No. SYXK(Zhe)2013-0184).
Conflict-of-interest statement: We declare that we have no financial and personal relationships with other people or organizations that can inappropriately influence our work, and there is no professional or other personal interest of any nature or kind in any product, service and/or company that could be construed as influencing the position presented in the manuscript entitled.
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: Jian-Nong Wu, MD, Chief Physician, Department of Intensive Care Unit, The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54 Post Road, Shangcheng District, Hangzhou 310006, Zhejiang Province, China. 13777571598@163.com
Received: July 20, 2021
Peer-review started: July 20, 2021
First decision: August 9, 2021
Revised: August 24, 2021
Accepted: October 18, 2021
Article in press: October 18, 2021
Published online: December 6, 2021
Processing time: 132 Days and 17.8 Hours
Abstract
BACKGROUND

Sepsis is a major medical challenge. Magnolol is an active constituent of Houpu that improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects, but the mechanism by which it reduces intestinal inflammation in sepsis is yet unclear.

AIM

To assess the protective effect of magnolol on intestinal mucosal epithelial cells in sepsis and elucidate the underlying mechanisms.

METHODS

Enzyme-linked immunosorbent assay was used to measure tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, and regulated on activation, normal T-cell expressed and secreted (RANTES) levels in serum and ileal tissue in animal studies. The histopathological changes of the ileal mucosa in different groups were observed under a microscope. Cell Counting Kit-8 and cell permeability assays were used to determine the concentration of drug-containing serum that did not affect the activity of Caco2 cells but inhibited lipopolysaccharide (LPS)-induced decrease in permeability. Immunofluorescence and Western blot assays were used to detect the levels of RANTES, inhibitor of nuclear factor kappa-B kinase β (IKKβ), phosphorylated IKKβ (p-IKKβ), inhibitor of nuclear factor kappa-B kinase α (IκBα), p65, and p-p65 proteins in different groups in vitro.

RESULTS

In rats treated with LPS by intravenous tail injection in the presence or absence of magnolol, magnolol inhibited the expression of proinflammatory cytokines, IL-1β, IL-6, and TNF-α in a dose-dependent manner. In addition, magnolol suppressed the production of RANTES in LPS-stimulated sepsis rats. Moreover, in vitro studies suggested that magnolol inhibited the increase of p65 nucleation, thereby markedly downregulating the production of the phosphorylated form of IKKβ in LPS-treated Caco2 cells. Specifically, magnolol inhibited the translocation of the transcription factor nuclear factor-kappa B (NF-κB) from the cytosol into the nucleus and down-regulated the expression level of the chemokine RANTES in LPS-stimulated Caco2 cells.

CONCLUSION

Magnolol down-regulates RANTES levels by inhibiting the LPS/NF-κB signaling pathways, thereby suppressing IL-1β, IL-6, and TNF-α expression to alleviate the mucosal barrier dysfunction in sepsis.

Keywords: Sepsis; Magnolol; Regulated on activation, normal T-cell expressed and secreted; Anti-inflammation; Lipopolysaccharide; Nuclear factor-kappa B

Core Tip: In this study, it was found that magnolol inhibited the lipopolysaccharide-induced nuclear factor-kappa B signaling pathway in the intestinal mucosal epithelium to regulate the secretion of regulated on activation, normal T-cell expressed and secreted (RANTES) and thus reduce intestinal inflammation in sepsis. Various biological constituents, isolated from traditional Chinese medicine, show multifunctional activities. Magnolol, isolated from Magnolia, has been documented to possess a range of biological activities. The current results for the first time proved that magnolol plays a role in the treatment of sepsis by down-regulating RANTES. Thus, additional studies on its anti-inflammatory mechanism might provide novel ideas and methods for the clinical prevention and treatment of sepsis.