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©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
Linolenic acid-metronidazole inhibits the growth of Helicobacter pylori through oxidation
Wen-Ting Zhou, Yuan-Yuan Dai, Li-Juan Liao, Shi-Xian Yang, Hao Chen, Liang Huang, Juan-Li Zhao, Yan-Qiang Huang
Wen-Ting Zhou, Li-Juan Liao, Liang Huang, Juan-Li Zhao, School of Basic Medicine, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Yuan-Yuan Dai, School of Basic Medicine, Youjiang Medical University for Nationalities, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Shi-Xian Yang, Department of Laboratory, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Hao Chen, School of Basic Medicine, Department of Pathology, Wannan Medical College, Wuhu 533000, Anhui Province, China
Liang Huang, Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Yan-Qiang Huang, School of Basic Sciences, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, China
Author contributions: Zhou WT and Dai YY consulted literature, performed experiments, collected and analyzed data and wrote the first draft, making equal contributions to this work; Liao LJ, Yang SX, and Chen H corrected it; Zhao LJ, Huang YQ, and Huang L designed, checked, modified, and completed the manuscript, making equal contributions to this work as co-corresponding authors; Huang L is the first corresponding author; and all authors approved the final version of the article.
Institutional review board statement: The study was reviewed and approved by the Institutional Review Board at Youjiang Medical University for Nationalities.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Data sharing statement: No additional data are available.
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:
https://creativecommons.org/Licenses/by-nc/4.0/ Corresponding author: Liang Huang, Instructor, Key Laboratory of the Prevention and Treatment of Drug Resistant Microbial Infecting, Youjiang Medical University for Nationalities, No. 98 Chengxiang Road, Baise 533000, Guangxi Zhuang Autonomous Region, China. youyihuangl@163.com
Received: May 31, 2023
Peer-review started: May 31, 2023
First decision: July 8, 2023
Revised: July 15, 2023
Accepted: July 31, 2023
Article in press: July 31, 2023
Published online: August 28, 2023
ARTICLE HIGHLIGHTS
Research background
Helicobacter pylori (H. pylori) is recognized as an important human pathogen associated with superficial gastritis, atrophic gastritis, gastric cancer, etc., each of which has become a serious threat to human health and survival. The rate of drug resistance is increasing due to the wide use of antibiotics and high rates of resistance to clarithromycin, metronidazole, and levofloxacin are associated with the failure of H. pylori eradication. At present, the mechanism of antibiotic resistance of H. pylori is not completely understood. It is very difficult to prevent drug resistance and improve the rate of eradication of the target, thus warranting exploration of the mechanism of drug resistance to H. pylori, and provision of an experimental basis for the prevention and treatment of drug resistance.
Research motivation
Currently, there is a serious drug resistance situation in H. pylori and new antibiotics are urgently needed; however, antibiotic research and development are very difficult. If we can understand the antibacterial mechanism of linolenic acid-metronidazole (Lla-Met), we can better apply it to antimicrobial treatment and solve the problem of antibiotic resistance.
Research objectives
The objectives of this study were to confirm the antibacterial effect of Lla-Met on H. pylori, and to provide theoretical support for further research and development of Lla-Met as an anti-H. pylori drug, and to help overcome the resistance of H. pylori to existing antibiotic drugs.
Research methods
H. pylori cells were treated with the Lla-Met compound, and the effect of the compound on the cell morphology, cell membrane permeability, and oxidation of the bacteria cell was assessed by scanning electron microscope, propidium iodide staining, FIFC-FD, detection of ion channels, detection of intracellular reactive oxygen species, and detection of phosphatidylserine ectropion. Meanwhile, the differently expressed genes in H. pylori in response to Lla-Met treatment were identified by transcriptome sequencing and quantitative real-time polymerase chain reaction.
Research results
The expression of both SodB and MdaB genes was up-regulated after treatment with Lla-Met, and both genes are associated with antioxidants. Lla-Met inhibits the growth of H. pylori through oxidation.
Research conclusions
The mechanism of linoleic-metronidazole compound was demonstrated to involve inhibiting H. pylori growth by inducing excessive reactive oxygen species accumulation, resulting in excessive superoxide dismutase MdaB and SodB genes expression.
Research perspectives
This study proves the antibacterial effect of Lla-Met on H. pylori at the molecular level, providing theoretical support for further research and development of Lla-Met as an anti-H. pylori drug to help overcome H. pylori resistance to current antibiotic drugs.
