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
ARTICLE HIGHLIGHTS
Research background

Sepsis is a major medical challenge, and finding specific targets and effective drugs is a scientific concern. Currently, various biological constituents are isolated from traditional Chinese medicine and have been confirmed to possess multifunctional activities.

Research motivation

Magnolol is an active constituent of Houpu, which improves tissue function and exerts strong anti-endotoxin and anti-inflammatory effects. Thus, we aimed to identify the role of magnolol in the treatment of sepsis.

Research objectives

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

Research methods

We carried out animal studies and cell studies in vitro, respectively. In animal studies, enzyme-linked immunosorbent assay was used to measure the differentially expressed inflammatory factors and regulated on activation, normal T-cell expressed and secreted (RANTES) levels in serum and ileal tissue. In the in vitro experiments, Cell Counting Kit-8 and cell permeability assays were employed to determine the concentration of drug-containing serum that did not affect the activity of Caco2 cells but inhibited lipopolysaccharide (LPS)-induced permeability reduction. Immunofluorescence and Western blot assays were used to detect the protein 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 in different groups.

Research results

In animal studies, magnolol inhibited the expression of proinflammatory cytokines tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β), and IL-6 in a dose-dependent manner and suppressed the production of RANTES in sepsis rats. In the in vitro studies, magnolol inhibited the increase of p65 nucleation and down-regulated the production of the phosphorylated form of IKKβ in LPS-treated Caco2 cells. Moreover, magnolol inhibited the translocation of the transcription factor nuclear factor-kappa B (NF-κB) from the cytosol into the nucleus and downregulated the expression level of the chemokine RANTES in LPS-stimulated Caco2 cells.

Research conclusions

Magnolol downregulates RANTES levels by inhibiting the LPS/NF-κB signaling pathway, resulting in the suppression of IL-1β, IL-6, and TNF-α expression that in turn, alleviates the mucosal barrier dysfunction in sepsis.

Research perspectives

This study, for the first time, proved that magnolol plays a role in the treatment of sepsis by down-regulating RANTES, and further studies on the anti-inflammatory mechanism might provide an in-depth insight into novel methods for the clinical prevention and treatment of sepsis.