Protective effect and mechanisms of action of Mongolian medicine Sulongga-4 on pyloric ligation-induced gastroduodenal ulcer in rats

doi:10.3748/wjg.v27.i16.1770

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World Journal of Gastroenterology

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1007-9327

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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.

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

ARTICLE HIGHLIGHTS

Research background

Sulongga-4 (SL-4) is a classic 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.

Research motivation

The study objective was to identify the protective effect and mechanism of SL-4 against peptic ulcer disease.

Research objectives

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

Research methods

PL was performed to induce gastric and duodenal ulcers in rats that 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 evaluated by pathological and histological evaluation. Inflammatory indicators were analyzed by enzyme-linked immunosorbent assay. Microarray analyses were conducted to determine the 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).

Research results

SL-4 improved the histopathology of the PL-induced ulcers. SL-4 significantly (P < 0.05) decreased the expression of tumor necrosis factor-α, interleukin (IL)-1β, IL-6, endotoxin, PAF, and increased prostaglandin E2 and EGF in ulcer tissue. Microarray analysis was used to identify a list of candidate target genes for SL-4 acting on PL-induced ulceration. The genes included some that modulate complement and coagulation cascade pathways, 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.

Research conclusions

SL-4 exerted protective effects against PL-induced gastroduodenal ulcers via reducing inflammatory cytokines and elevating the expression of gastric acid inhibitory factors. Downregulation of the CYP2b2 and UGT2b1 genes in retinol metabolism and upregulation of the A2m and MASP1 genes in the complement and coagulation cascade pathways may have been involved in the protection against gastroduodenal ulcers.

Research perspectives

SL-4, a Mongolian folk medicine, is a promising gastroprotective agent with potential clinical use as a treatment of gastric ulcers.