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Gastroprotective activity of polysaccharide from the fruiting body of Hericium erinaceus against acetic acid-induced gastric ulcer in rats and structure of one bioactive fraction

Date:2022-6-17 10:22:07   

Gastric ulcer is a common upper gastrointestinal disease with long treatment period and high recurrence rate, which has a huge impact on people's quality of life. At present, the clinical treatment of gastric ulcer mainly relies on drugs, such as antibiotics, antacids, proton pump inhibitors (PPIs), histamine H2 receptor antagonists, etc. However, the use of these drugs brings side effects and complications. Therefore, it is necessary to explore high-efficiency and low-toxic alternatives to the above drugs for the treatment of gastric ulcers.


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So far, a large number of mushroom polysaccharides have been reported to relieve gastric ulcers in animal experiments. For example, polysaccharides from fruiting bodies of Ganoderma lucidum have been shown to improve gastric ulcers in rats induced by acetic acid and indomethacin; polysaccharides from fruiting bodies of Gallinarum have a healing effect on gastric ulcers in mice induced by indomethacin; fruiting bodies of oyster mushrooms Polysaccharide has inhibitory effect on acetic acid-induced gastric ulcer in rats.


      Polysaccharide is one of the main bioactive substances in Hericium erinaceus, which is mainly extracted from the fruiting body. Hericium erinaceus polysaccharide (HEP) has various biological activities, including gastroprotective effects. In previous studies, HEP was shown to prevent acute gastric ulcers caused by ethanol and pyloric ligation, but its therapeutic effect on chronic gastric ulcers has not been disclosed. On the other hand, the active components or structures in HEP that protect the gastric mucosa are rarely reported. Therefore, in this study, an acetic acid-induced rat chronic gastric ulcer model was used to evaluate the healing effect of HEP from fruiting bodies on gastric ulcer, and screened out the purified bioactive components of HEP, and at the same time, one of the active components was structurally characterized . On the basis of previous work, five purified polysaccharides (RP-50, RP-60, RP-70, RP-80 and RP-S) were obtained from HEP and induced GES-1 injury in human gastric mucosal epithelial cells using H2O2 The method screened the biologically active components, and determined the primary structure of one of the active components by methylation analysis and nuclear magnetic resonance spectroscopy.


 The acid-induced chronic gastric ulcer model is suitable for evaluating the gastric ulcer healing activity of substances, since gastric ulcers of this type are similar to human chronic ulcers, especially in terms of pathology and healing process. The results of this study showed that the fruiting body HEP had a healing effect on acetic acid-induced gastric ulcer in rats, which was similar to the effect of other polysaccharides in the fruiting bodies of Ganoderma lucidum and oyster mushroom. Combined with previous studies, it was found that fruiting body HEP has a preventive effect on acute gastric ulcer induced by ethanol or pyloric ligation. It can be speculated that fruiting body HEP may be a drug for the prevention and treatment of gastric ulcer. The occurrence of acetic acid-induced gastric ulcer is related to the changes of prostaglandins, growth factors, NO, cytokines, mucoadhesion patterns and microcirculation. The present study showed that the levels of PGE2, growth factors (EGF, VEGF, and bFGF) and NO were significantly decreased, and the contents of pro-inflammatory cytokines (IL-6 and TNF-α) were significantly increased in the gastric tissue of rats induced by acetic acid. Supplementation with fruiting body HEP in ulcerated rats reversed these changes. On the other hand, after acetic acid stimulation of the gastric mucosa, reactive oxygen species overexpression can directly or indirectly attack the tissue and induce oxidative damage, thereby promoting the formation of ulcers. This study suggests that acetic acid induces oxidative damage in rat gastric tissue, which is manifested as a decrease in SOD activity and an increase in MDA content. Oral HEP can alleviate oxidative damage by improving the body's antioxidant status. Additionally, peroxidase (MPO) was used as an indirect marker of neutrophil migration at ulcer sites. The results showed that acetic acid induced a significant increase in MPO activity in rat gastric tissue, and HEP treatment of fruiting bodies could alleviate this change. Therefore, it can be considered that the mechanism of action of fruiting body HEP in the improvement of acetic acid-induced gastric ulcer may be to increase the release of gastric defense factors, anti-inflammatory and improve antioxidant status.


 A continuous layer of surface epithelial cells forms a gastric mucosal line of defense. Human gastric epithelial cell GES-1 has been widely used to evaluate the cytoprotective effect of polysaccharides against H2O2- or ethanol-induced oxidative stress injury. Through H2O2-induced GES-1 cell model, five purified HEP polysaccharides (RP-50, RP-60, RP-70, RP-80 and RP-S) were screened out as active components, which had no significant cytoprotective effect difference. The biological activity of polysaccharides is closely related to its structure. Previous studies have shown that the five purified polysaccharides differ in chemical composition and molecular weight. In order to better explain the above phenomenon, it is necessary to further determine the structural characteristics of other polysaccharides. RP-S can reduce the content of MDA in GES-1 cells by increasing the activities of SOD and GSH-Px, and attenuate H2O2-induced cellular oxidative damage. The protective effect of RP-S against H2O2-induced damage was similar to that of purified HEP fractions obtained from fruiting bodies in other studies. However, RP-S is a new type of polysaccharide purified from the fruiting body of Hericium erinaceus, and its physicochemical properties and structural characteristics are quite different from those reported in previous studies. The molecular weight of RP-S is 2.1 kDa, and the main component is glucose. In this study, structural characterization revealed that RP-S has the potential to repeat the unit (1→6)-β-D-glucan, and the O-3 position is T-β-D-glucopyranosyl-(1→residue branch.


     In summary, HEP has the potential to replace anti-gastric ulcer drugs, (1→6)-β-D-glucan is a biologically active structure in HEP, and future work will focus on other biologically active components. Structure Characterization.