The Protective Effects of 18β-Glycyrrhetinic Acid on Helicobacter pylori-Infected Gastric Mucosa in Mongolian Gerbils

Abstract

18β-Glycyrrhetinic acid (GRA), a major component of Glycyrrhiza glabra, is widely used therapeutically in clinic. In this study, the effect of GRA on Helicobacter pylori- (H. pylori-) infected gastritis was investigated in Mongolian gerbils in vivo. The gerbils were randomly divided into groups: uninfected; H. pylori-infected; H. pylori + antibiotics (clarithromycin, amoxicillin, and esomeprazole); and H. pylori + GRA. The gastric intraluminal pH value, histopathological changes, and the expression levels of inflammation-related cytokines (IL-1β, TNF-α, COX-2, and iNOS) were investigated. The results showed that, in the H. pylori + GRA group, the intraluminal gastric pH value was lower (2.14 ± 0.08 versus 3.17 ± 0.23, P < 0.05), erosion and hyperplasia were alleviated, the infiltration of neutrophils and mononuclear cells was attenuated (P < 0.05), and the expression levels of TNF-α, IL-1β, COX-2, and iNOS were decreased (P < 0.05) compared with the H. pylori-infected group. There was no significant difference in results between the H. pylori + GRA group and the H. pylori + antibiotics group. This study indicated that GRA significantly attenuated H. pylori-infected gastritis in gerbils and has the potential to be developed as a new therapeutic drug.

Figure 1

Experimental design.

Figure 2

Gastric intraluminal pH values of Mongolian gerbils 12 weeks after infection with Helicobacter pylori and either antibiotics therapy treatment or 18β-Glycyrrhetinic acid (GRA); ^∗∗∗ P < 0.001.

Figure 3

The macroscopic gastric mucosa findings in gerbils infected by Helicobacter pylori (upper panel: (a) hyperemia; (b) erosion; (c) hyperplasia), after antibiotics treatment (e) or 18β-Glycyrrhetinic acid (GRA) (f). Uninfected gerbils were controls (d).

Figure 4

Histopathological analysis of the gastric mucosa in gerbils infected by Helicobacter pylori (upper panel: (a) hyperplasia; (b) erosion; (c) superficial ulcer) after antibiotics treatment (e) or 18β-Glycyrrhetinic acid (f). Uninfected gerbils were controls (d). H&E; ×40.

Figure 5

Relative expression levels of COX-2, IL-1β, iNOS, and TNF-α mRNA in glandular corpus (a) and antrum (b) of Mongolian gerbils infected with Helicobacter pylori for 12 weeks and treated with either antibiotics or 18β-Glycyrrhetinic acid. Values were set at 1.0 in Group A (uninfected controls) and expressed as mean ± SE relative values. ^∗ P < 0.05, ^∗∗ P < 0.01.