Clinical and Translational Research
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Clin Cases. Dec 6, 2022; 10(34): 12500-12514
Published online Dec 6, 2022. doi: 10.12998/wjcc.v10.i34.12500
Coptis, Pinellia, and Scutellaria as a promising new drug combination for treatment of Helicobacter pylori infection
Zhang Yu, Wu-Dong Sheng, Xu Yin, Yu Bin
Zhang Yu, Xu Yin, Yu Bin, Department of Internal Medicine, The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, Hunan Province, China
Wu-Dong Sheng, Department of Surgery, The First Hospital of Hunan University of Chinese Medicine, Changsha 410007, Hunan Province, China
Author contributions: Bin Y initiated the project; Yu Z and Sheng WD had the idea for this study and performed the experiments; Yu Z wrote the manuscript; Bin Y and Yin X performed the experiments and wrote the manuscript; all authors contributed to the final manuscript.
Supported by the Domestic First-class Construction Disciplines of the Hunan University of Chinese Medicine, No. 2018[03]; the Key Scientific Research Project of Hunan Provincial Education Board, No. 20A371; and the Key Programs of Administration of Traditional Chinese Medicine of Hunan Province, No. C2022016.
Institutional review board statement: The study was reviewed and approved by The First Hospital of Hunan University of Chinese Medicine Institutional Review Board (Approval No. ZYFY20190620).
Conflict-of-interest statement: None of the authors have any conflicts of interest to declare.
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: Yu Bin, MM, Chief Physician, Professor, Department of Internal Medicine, The First Hospital of Hunan University of Chinese Medicine, No. 95 Shaoshan Middle Road, Yuhua District, Changsha 410007, Hunan Province, China. yubin410@163.com
Received: July 23, 2022
Peer-review started: July 23, 2022
First decision: September 26, 2022
Revised: October 9, 2022
Accepted: November 7, 2022
Article in press: November 7, 2022
Published online: December 6, 2022
Processing time: 132 Days and 1.4 Hours
Abstract
BACKGROUND

Helicobacter pylori (H. pylori) is the most important infectious agent and plays an important role in the progression of chronic gastritis and the development of gastric cancer.

AIM

To identify efficient therapeutic agents or strategies that can treat H. pylori infection.

METHODS

We performed literature analysis, experimental validation, and network pharmacology. First, traditional Chinese medicine (TCM) prescriptions for the treatment of H. pylori infection were obtained from the China National Knowledge Infrastructure, China Biology Medicine, China Science and Technology Journal Database, and WanFang databases. In addition, we conducted a relevant search by Reference Citation Analysis (RCA) (https://www.referencecitationanalysis.com). Next, we used TCM Inheritance Support System V2.5 to identify core drug combinations in the TCM prescriptions. Then, an H. pylori-associated chronic mouse model of gastritis was established. The antibacterial properties and anti-inflammatory potential of the core drug combination were evaluated by the rapid urease test, modified Warthin-Starry silver staining, histopathological analysis, and enzyme linked immunosorbent assay. Finally, the active compounds, hub targets, and potential signaling pathways associated with the core drug combination were analyzed by network pharmacology.

RESULTS

The TCM treatment of H. pylori was mainly based on reinforcing the healthy Qi and eliminating pathogenic factors by simultaneously applying pungent dispersing, bitter descending, cold and warm drugs. The combination of Coptis, Pinellia, and Scutellaria (CPS) was identified as the core drug combination from 207 prescriptions and 168 herbs. This drug combination eradicated H. pylori, alleviated the gastric pathology induced by H. pylori infection, and reduced the expression levels of tumor necrosis factor-α (P = 0.024) and interleukin-1β (P = 0.001). Moreover, a total of 35 compounds and 2807 targets of CPS were identified using online databases. Nine key compounds (tenaxin I, neobaicalein, norwogonin, skullcapflavone II, baicalein, 5,8,2'-trihydroxy-7-methoxyflavone, acacetin, panicolin, and wogonin) and nine hub target proteins (EGFR, PTGS2, STAT3, MAPK3, MAPK8, HSP90AA1, MAPK1, MMP9, and MTOR) were further explored. Seventy-seven signaling pathways were correlated with H. pylori-induced inflammation and carcinogenesis.

CONCLUSION

In summary, we showed that CPS is the core drug combination for treating H. pylori infection. Animal experiments demonstrated that CPS has bacteriostatic properties and can reduce the release of inflammatory cytokines in the gastric mucosa. Network pharmacology predictions further revealed that CPS showed complex chemical compositions with multi-target and multi-pathway regulatory mechanisms. Although the results derived from network pharmacology are not necessarily comprehensive, they still expand our understanding of CPS for treating H. pylori infection.

Keywords: Coptis; Pinellia; Scutellaria; Anti-Helicobacter pylori; Drug combination; Traditional Chinese medicine

Core Tip: Infection with Helicobacter pylori (H. pylori) is associated with severe digestive diseases, while successful eradication of this pathogen is known to prevent the occurrence of peptic ulcer disease and gastric cancer. Traditional Chinese medicine (TCM) has unique advantages for treating H. pylori infection, which can reduce drug resistance and increase the eradication rate of H. pylori. Here, we attempted to identify medication rules, effective materials, and the molecular mechanisms underlying the therapeutic effect of TCM against H. pylori using data mining, in vivo experiment, and network pharmacology. Coptis, Pinellia, and Scutellaria (CPS) were identified as the core drug combination for H. pylori eradication. We evidenced that CPS eradicated H. pylori, alleviated the gastric pathology, and reduced circulating tumor necrosis factor-α and interleukin-1β levels. Nine key compounds and nine hub target proteins were further determined as the key active ingredients and therapeutic targets of CPS against H. pylori, respectively. Altogether, our data strongly suggest that the efficacy of CPS in the treatment of H. pylori is worthy of affirmation.