Basic Study
Copyright ©The Author(s) 2021. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Apr 28, 2021; 27(16): 1770-1784
Published online Apr 28, 2021. doi: 10.3748/wjg.v27.i16.1770
Protective effect and mechanisms of action of Mongolian medicine Sulongga-4 on pyloric ligation-induced gastroduodenal ulcer in rats
Shan Tong, Huan Wang, Li-Sha A, Ta-Na Bai, Ju-Hua Gong, Wen-Jie Jin, Li-Li Dai, Gen-Na Ba, Sung-Bo Cho, Ming-Hai Fu
Shan Tong, Huan Wang, Li-Sha A, Ta-Na Bai, Ju-Hua Gong, Wen-Jie Jin, Li-Li Dai, Gen-Na Ba, Sung-Bo Cho, Ming-Hai Fu, School of Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao 028000, Inner Mongolia Autonomous Region, China
Shan Tong, Mongolian Medicine Surgery Department, Affiliated Hospital of Inner Mongolia University for Nationalities, Tongliao 028000, Inner Mongolia Autonomous Region, China
Li-Sha A, Wen-Jie Jin, Li-Li Dai, Ming-Hai Fu, Traditional Mongolian Medicine Research Institute, Inner Mongolia University for Nationalities, Tongliao 028000, Inner Mongolia Autonomous Region, China
Author contributions: Tong S, Wang H and Fu MH conceived and designed the project; Tong S, Wang H, Jin WJ and Dai LL performed the experiments; Bai TN and Gong JH performed the animal experiment; Cho SB, A LS, Ba GN and Fu MH performed microarray data analysis and interpreted the results; Cho SB and Fu MH wrote the manuscript; All authors have read and approved the final manuscript.
Supported by Mongolian Medicine Food and Drug Source Protection and Utilization Innovation Team Construction Project, No. 190301; National Natural Science Foundation of China, No. 81760765; Inner Mongolia University for Nationalities Doctoral Start-up Grant, No. BS412 and No. BS413; Mongolian Medicine Engineering Technology Research Centre Open Fund Project, No. MDK2017072; and Inner Mongolia Autonomous Region Talent Development Fund Project, No. RC201802.
Institutional animal care and use committee statement: This research was reviewed and approved by the Committee on the Ethics of Animal Experiments of Inner Mongolia University for Nationalities.
Conflict-of-interest statement: The authors declare that they have no competing interests.
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: Ming-Hai Fu, PhD, Associate Professor, School of Mongolian Medicine, Inner Mongolia University for Nationalities, No. 996 Xilamulun Street, Tongliao 028000, Inner Mongolia Autonomous Region, China. mfu@imun.edu.cn
Received: November 20, 2020
Peer-review started: November 20, 2020
First decision: December 17, 2020
Revised: January 29, 2021
Accepted: March 24, 2021
Article in press: March 24, 2021
Published online: April 28, 2021
Processing time: 152 Days and 2.4 Hours
Abstract
BACKGROUND

Sulongga-4 (SL-4) is a herbal formula used in traditional Mongolian medical clinics for the treatment of peptic ulcers and gastroenteritis, even though its pharmacological mechanism has not been well characterized.

AIM

To evaluate the protective effect and identify the mechanisms of action of SL-4 on gastroduodenal ulcer induced by pyloric ligation (PL) in rats.

METHODS

PL was performed to induce gastric and duodenal ulcers in rats, which were then treated with oral SL-4 (1.3, 2.6, or 3.9 g/kg per day) for 15 d. PL-induced gastroduodenal ulceration. Therapeutic effects were characterized by pathological and histological evaluations and inflammatory indicators were analyzed by enzyme-linked immunosorbent assay. Microarray analyses were conducted to identify gene expression profiles of gastroduodenal tissue in PL rats with or without SL-4 treatment. The candidate target genes were selected and verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR).

RESULTS

SL-4 decreased histopathological features in the PL-induced ulcerated rats. SL-4 significantly (P < 0.05) decreased expression of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, endotoxin, platelet-activating factor, and increased prostaglandin E2 and epidermal growth factor in ulcer tissue. Microarray analysis was used to identify a panel of candidate target genes for SL-4 acting on PL-induced ulceration. Genes included some complement and coagulation cascade and retinol metabolism pathways that are closely associated with inflammatory responses and gastric mucosal protective mechanisms. qRT-PCR showed that altered expression of the selected genes, such as CYP2b2, UGT2b1, A2m, and MASP1 was consistent with the microarray results.

CONCLUSION

SL-4 exerts protective effects against PL-induced gastroduodenal ulcers via reducing inflammatory cytokines and elevating expression of gastric acid inhibitory factors. Downregulation of CYP2b2 and UGT2b1 genes in retinol metabolism and upregulation of A2m and MASP1 genes in the complement and coagulation cascades pathways are possibly involved in SL-4-mediated protection against gastroduodenal ulcer.

Keywords: Sulongga-4; Peptic ulcer; Pyloric ligation; Microarray analysis; Inflammatory reaction; Retinol metabolism

Core Tip: Sulongga-4 (SL-4) is a classic herbal formula used in Mongolian medical clinics for the treatment of peptic ulcers and gastroenteritis. This study investigated the protective effects and molecular mechanisms of SL-4 in pyloric ligation (PL)-induced gastroduodenal ulcers in rats via microarray analysis. Our results suggest that SL-4 was strongly protective against PL-induced gastroduodenal ulcers via reducing inflammatory cytokines and elevating the expression of gastric acid inhibitory factors. Downregulation of CYP2b2 and UGT2b1, and upregulation of A2m and MASP1 may be involved in the gastroduodenal ulcer protection mechanism of SL-4.