Basic Study
Copyright ©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. May 14, 2023; 29(18): 2818-2835
Published online May 14, 2023. doi: 10.3748/wjg.v29.i18.2818
BanXiaXieXin decoction treating gastritis mice with drug-resistant Helicobacter pylori and its mechanism
Xiao-Hua Li, Jia-Yin Xu, Xue Wang, Li-Juan Liao, Liang Huang, Yan-Qiang Huang, Zeng-Feng Zhang
Xiao-Hua Li, Duate School, Guangxi Medical University, Nanning 5330021, Guangxi Zhuang Autonomous Region, China
Jia-Yin Xu, Xue Wang, Li-Juan Liao, Yan-Qiang Huang, Guangxi Technology Innovation Cooperation Base of Prevention and Control Pathogenic Microbes with Drug Resistance, Youjiang Medical University for Nationalities, Baise 533000, Guangxi Zhuang Autonomous Region, 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
Zeng-Feng Zhang, Department of Microbiology, Guangxi Medical University, Nanning 530021, Guangxi Zhuang Autonomous Region, China
Author contributions: Li XH and Xu JY consulted literature, performed experiments, collected and analyzed data and wrote the first draft, making equal contributions to this work; Wang X and Liao LJ corrected it; Huang L, Huang YQ, and Zhang ZF designed, checked, modified, and completed the manuscript, making equal contributions to this work as co-corresponding authors, Huang L (youyihuangl@163.com) is the first corresponding author; all authors approved the final version of the article.
Supported by the National Natural Science Foundation of China, No. 81760739; Special Fund Projects for Guide Local Science and Technology Development by the China government, No. GUIKEZY20198004; and 2022 Guangxi Graduate Education Innovation Plan Project, No. YCBZ2022071.
Institutional animal care and use committee statement: All procedures involving animals were reviewed and approved by the Youjiang Medical University for Nationalities Institutional Review Board (approval No. 20220110).
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
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: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zeng-Feng Zhang, professor, Department of Microbiology, Guangxi Medical University,No.22 Shuangyong Road, Nanning, 530021, Guangxi Zhuang Autonomous Region, China. zfzhangphd@163.com
Received: February 28, 2023
Peer-review started: February 28, 2023
First decision: March 14, 2023
Revised: March 16, 2023
Accepted: April 13, 2023
Article in press: April 13, 2023
Published online: May 14, 2023
Processing time: 70 Days and 7.6 Hours
Abstract
BACKGROUND

Helicobacter pylori (H. pylori) is the main pathogen that causes a variety of upper digestive diseases. The drug resistance rate of H. pylori is increasingly higher, and the eradication rate is increasingly lower. The antimicrobial resistance of H. pylori is an urgent global problem. It has been confirmed that Banxia Xiexin decoction (BXXXT) demonstrates the effects of treating gastrointestinal diseases, inhibiting H. pylori and protecting gastric mucosa. The purpose of the present study is to further explore the therapeutic effects of BXXXT on drug-resistant H. pylori.

AIM

To confirm that BXXXT demonstrates therapeutical effects in vivo and in vitro on gastritis mice with drug-resistant H. pylori and explain its mechanism to provide an experimental basis for promoting the application of BXXXT.

METHODS

The aqueous extract of BXXXT was gained by water decocting method. The inhibitory effect of the aqueous extract on H. pylori was detected by dilution in vitro; drug-resistant H. pylori cells were used to build an acute gastritis model in vivo. Thereafter, the model mice were treated with the aqueous extract of BXXXT. The amount of H. pylori colonization, the repair of gastric mucosal damage, changes of inflammatory factors, apoptosis, etc., were assessed. In terms of mechanism exploration, the main medicinal compositions of BXXXT aqueous extract and the synergistic bacteriostatic effects they had demonstrated were analyzed using mass spectrometry; the immune function of peripheral blood cells such as CD3+ T and CD4+ T of mice with gastritis before and after treatment with BXXXT aqueous extract was detected using a flow cytometry; the H. pylori transcriptome and proteome after treatment with BXXXT aqueous extract were detected. Differently expressed genes were screened and verification was performed thereon with knockout expression.

RESULTS

The minimum inhibitory concentration of BXXXT aqueous extract against H. pylori was 256-512 μg/mL. A dose of 28 mg/kg BXXXT aqueous extract treatment produced better therapeutical effects than the standard triple therapy did; the BXXXT aqueous extract have at least 11 ingredients inhibiting H. pylori, including berberine, quercetin, baicalin, luteolin, gallic acid, rosmarinic acid, aloe emodin, etc., of which berberine, aloe emodin, luteolin and gallic acid have a synergistic effect; BXXXT aqueous extract was found to stimulate the expressions of CD3+ T and CD4+ T and increase the number of CD4+ T/CD8+ T in gastritis mice; the detection of transcriptome and proteome, quantitative polymerase chain reaction, Western blotting and knockout verification revealed that the main targets of BXXXT aqueous extract are CFAs related to urea enzymes, and CagA, VacA, etc.

CONCLUSION

BXXXT aqueous extract could demonstrate good therapeutic effects on drug-resistance H. pylori in vitro and in vivo and its mechanism comes down to the synergistic or additional antibacterial effects of berberine, emodin and luteolin, the main components of the extract; the extract could activate the immune function and enhance bactericidal effects; BXXXT aqueous extract, with main targets of BXXXT aqueous extract related to urease, virulence factors, etc., could reduce the urease and virulence of H. pylori, weaken its colonization, and reduce its inflammatory damage to the gastric mucosa.

Keywords: Banxia Xiexin decoction; Helicobacter pylori; Drug resistance; Therapeutic effects; Mechanism

Core Tip: The failure rate of treating Helicobacter pylori (H. pylori) infectious diseases is increasing, leading to an urgent need to study and develop anti-H. pylori drugs. Banxia Xiexin decoction (BXXX) has a good effect on Hp infection and Hp-infection-related diseases. However, its pharmacological mechanism remains unclear, and whether it has an effect on drug-resistant H. pylori infection has not been confirmed by animal experiments. Our study confirms that BXXX decoction (BXXXT) has good therapeutic effects on drug-resistant H. pylori infection through in vivo and in vitro experiments in mice, then the composition of BXXXT and effective components, the immunomodulatory effect, the main target were verified. We preliminarily explain why BXXXT has a good effects.