Effects of pomegranate exocarp extract on H. pylori-induced pancreatic EMT: Molecular mechanisms and therapeutic potential

Background

Previous studies have linked Helicobacter pylori infection with pancreatic diseases, including cancer.

Purpose

To explore the influence of pomegranate exocarp extract (PEE) on epithelial-mesenchymal transition (EMT) in H. pylori-induced pancreatic rat tissue and to uncover the underlying molecular mechanisms.

Study design

Twenty-eight rats were divided into six groups: group 1 (negative control), group 2 (H. pylori-infected), group 3 (infected + PEE pretreatment), group 4 (infected + PEE treatment), group 5 (infected + metronidazole treatment), and group 6 (infected + metronidazole/PEE co-treatment).

Methods and results

This study aimed to assess the effectiveness of pomegranate exocarp extract (PEE) in treating Helicobacter pylori infection and its associated pancreatic tissue changes in Wistar rats. The study involved Forty-eight male rats divided into six groups: H. pylori-infected control, PEE-preventive, PEE treatment, metronidazole treatment, PEE combined with metronidazole treatment, and negative control. The results showed a significant reduction in H. pylori concentration in the antrum in the PEE-treated groups (27.08 %) compared to that in the positive control group (p < 0.05). The group receiving the combined treatment exhibited the highest reduction (55.8 %) in H. pylori concentration (p < 0.005), with no significant difference observed between the PEE-preventive and metronidazole-treated groups. The ELISA results showed that the groups treated with PEE, PEE-preventive, and PEE combined with metronidazole experienced a significant increase in pancreatic E-cadherin levels by 47.7 %, 73.8 %, and 118.06 % respectively, and a substantial decrease in vimentin levels by 16.6 %, 31.6 %, and 43.5 % respectively, compared to the positive control group (p < 0.05). The results of the RT-qPCR analysis showed that the PEE treatment group, as well as the PEE preventive and PEE combined with metronidazole treatment groups, displayed significant downregulation of vimentin, sirtuin1, and lncRNA MALAT-1, and upregulation of E-cadherin compared to the positive control group. However, there was no significant difference between the PEE-preventive and metronidazole-treated groups (p < 0.05). Histopathological analysis showed considerable improvement in pancreatic tissue morphology in the PEE-treated groups. The inflammation score was significantly lower in these groups (p < 0.05), and the combined treatment group exhibited minimal signs of metaplasia and mononuclear cell infiltration. A computational study identified 54 human target genes of bioactive compounds in PEE. These findings shed light on the crucial interactions and pathways in treating pancreatic tumors. Additionally, GO enrichment and KEGG pathway analyses revealed significant pathways, such as the MAPK signaling and RTK pathway, enriched with genes targeted by PEE. Furthermore, evaluation of drug-likeness and ADME properties indicated that ellagic acid possesses drug-like properties and has a high potential for oral absorption. In conclusion, PEE has shown significant therapeutic potential in reducing H. pylori load and improving pancreatic tissue health while influencing key molecular markers and pathways associated with pancreatic tumors.