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. 2023 Dec;28(1):2218679.
doi: 10.1080/13510002.2023.2218679.

Genistein ameliorated experimentally induced gastric ulcer in rats via inhibiting gastric tissues fibrosis by modulating Wnt/β-catenin/TGF-β/PKB pathway

Hanan M Hassan  1 , Nouf M Alatawi  2 , Alaa Bagalagel  3 , Reem Diri  3 , Ahmad Noor  3 , Deina Almasri  3 , Hussain T Bakhsh  3 , Hussam I Kutbi  3 , Noha Ashy  3 , Mohammed M H Al-Gayyar  4   5
Affiliations

Genistein ameliorated experimentally induced gastric ulcer in rats via inhibiting gastric tissues fibrosis by modulating Wnt/β-catenin/TGF-β/PKB pathway

Hanan M Hassan et al. Redox Rep. 2023 Dec.

Abstract

Objectives: Gastric ulcer (GU) is a prevalent chronic digestive disease affecting about 10% of the world's population leading to gastrointestinal perforation and bleeding. Genistein is a legume flavonoid with antioxidants, anti-inflammatory and antibacterial activities. Therefore, we aimed to investigate the ability of genistein to reduce experimentally induced GU in rats by affecting gastric tissue fibrosis Wnt/β-catenin/TGF-β/SMAD4 pathway.

Methods: Thirty rats were used. Ten rats served as control, and GU was induced in twenty rats using a single dose of indomethacin (80 mg/kg) orally. Following induction of GU, ten were treated with genistein 25 mg/kg orally. The gastric tissues were isolated to investigate markers of gastric fibrosis, Wnt, β-catenin, transforming growth factor (TGF)-β, SMAD4, and Protein kinase B (PKB). In addition, gastric sections were stained with PAS and anti-TGF-β antibodies.

Results: Investigation GU micro-images revealed degeneration in both surface cells and glandular epithelial cells, which was improved by genistein. In addition, treatment with genistein significantly reduced the expression of Wnt, β-catenin, TGF-β, SMAD4, and PKB.

Conclusion: Besides antioxidant activity, genistein improves experimentally induced GU in rats, at least in part, via reduction of gastric tissue fibrosis as indicated by reduction in expression of Wnt, β-catenin, TGF-β, SMAD4, and PKB.

Keywords: SMAD4; Wnt; catalase; gastric ulcer; hydrogen peroxide; malondialdehyde (MDA); protein kinase B (PKB); superoxide dismutase (SOD); transforming growth factor (TGF)-β; β-catenin.

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Conflict of interest statement

No potential conflict of interest was reported by the author(s).

Figures

Figure 1.
Figure 1.
Effect of gastric ulcer (GU) and 25 mg/kg genistein on stomach morphology (a), showing normal appearance of the stomach from a control rat. The stomach of the GU rat showed mucosal hemorrhagic lesions and areas of ulceration. The stomach from the genistein group showed great reduction in hemorrhage and ulcer areas. (b) represented gastric solution pH, (c) represented mucus production and (d) represented stomach/body weight ratio (d). * Significant difference as compared with control group at p < 0.05. # Significant difference as compared with GU group at p < 0.05.
Figure 2.
Figure 2.
Gastric sections stained with PAS showing normal pink stained mucous content in mucosal layer in control group (a), glandular gastric sections from gastric ulcer group with marked deficiency in mucosal layer as indicated by the yellow arrows (b) and partial restoration of mucosal layer in gastric ulcer group treated with genistein (c). Scale bar 100 µm.
Figure 3.
Figure 3.
Effect of gastric ulcer (GU) and 25 mg/kg genistein on gastric oxidative stress and antioxidant markers. (a) Malondialdehyde (MDA), (b) hydrogen peroxide, (c) catalase and (d) superoxide dismutase (SOD) levels. * Significant difference as compared with control group at p < 0.05. # Significant difference as compared with GU group at p < 0.05.
Figure 4.
Figure 4.
Effect of gastric ulcer (GU) and 25 mg/kg genistein on gene expression of Wnt (a) and β-catenin (b) as well as the gastric level of β-catenin (c). * Significant difference as compared with control group at p < 0.05. # Significant difference as compared with GU group at p < 0.05.
Figure 5.
Figure 5.
Effect of gastric ulcer (GU) and 25 mg/kg genistein on gene expression of transforming growth factor (TGF)-β (a) and its protein level in gastric tissues (b). Gastric sections stained with anti-TGF-β in control group (c), GU group (d) and GU treated with genistein (e), as well as immunohistochemistry score of positive staining (f). Blue arrows indicated areas of immunostaining. Scale bar 100 μm. * Significant difference as compared with control group at p < 0.05. # Significant difference as compared with GU group at p < 0.05.
Figure 6.
Figure 6.
Effect of gastric ulcer (GU) and 25 mg/kg genistein on gene expression of suppressor of Mothers against Decapentaplegic (SMAD)4 (a) and its gastric protein level (b). * Significant difference as compared with control group at p < 0.05. # Significant difference as compared with GU group at p < 0.05.
Figure 7.
Figure 7.
Effect of gastric ulcer (GU) and 25 mg/kg genistein on gene expression of protein kinase B (PKB) (a) and its gastric protein level (b). * Significant difference as compared with control group at p < 0.05. # Significant difference as compared with GU group at p < 0.05.
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