Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt.
Department of Biochemistry, Faculty of Pharmacy, Tanta University, Tanta 31527, Egypt; Department of Biochemistry, Faculty of Pharmacy, AlSalam University, Kafr alzayat, Algharbia 31611, Egypt.
Cell Signal. 2024 Dec;124:111465. doi: 10.1016/j.cellsig.2024.111465. Epub 2024 Oct 10.
Previous studies have linked Helicobacter pylori infection with pancreatic diseases, including cancer.
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.
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).
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.
先前的研究表明，幽门螺杆菌感染与胰腺疾病（包括癌症）有关。
探索石榴外果皮提取物（PEE）对幽门螺杆菌诱导的大鼠胰腺组织上皮-间充质转化（EMT）的影响，并揭示其潜在的分子机制。
将 28 只大鼠分为六组：第 1 组（阴性对照）、第 2 组（幽门螺杆菌感染）、第 3 组（感染+PEE 预处理）、第 4 组（感染+PEE 治疗）、第 5 组（感染+甲硝唑治疗）和第 6 组（感染+甲硝唑/PEE 联合治疗）。
本研究旨在评估石榴外果皮提取物（PEE）在治疗幽门螺杆菌感染及其相关胰腺组织变化方面的疗效。研究涉及 48 只雄性大鼠，分为六组：幽门螺杆菌感染对照、PEE 预防、PEE 治疗、甲硝唑治疗、PEE 联合甲硝唑治疗和阴性对照。结果显示，与阳性对照组相比，PEE 治疗组胃窦部幽门螺杆菌浓度显著降低（27.08%）（p<0.05）。联合治疗组幽门螺杆菌浓度降低幅度最高（55.8%）（p<0.005），与 PEE 预防组和甲硝唑治疗组无显著差异。ELISA 结果显示，与阳性对照组相比，PEE、PEE 预防和 PEE 联合甲硝唑治疗组的胰腺 E-钙黏蛋白水平分别显著升高 47.7%、73.8%和 118.06%，波形蛋白水平分别显著降低 16.6%、31.6%和 43.5%（p<0.05）。RT-qPCR 分析结果显示，PEE 治疗组、PEE 预防组和 PEE 联合甲硝唑治疗组的波形蛋白、沉默调节蛋白 1（Sirtuin1）和长链非编码 RNA MALAT-1 表达显著下调，E-钙黏蛋白表达显著上调，与阳性对照组相比，差异有统计学意义（p<0.05）。然而，PEE 预防组和甲硝唑治疗组之间没有显著差异（p<0.05）。组织病理学分析显示，PEE 治疗组的胰腺组织形态有了相当大的改善。这些组的炎症评分显著降低（p<0.05），联合治疗组表现出最小的化生和单核细胞浸润迹象。计算研究确定了 PEE 中 54 种生物活性化合物的人类靶基因。这些发现揭示了治疗胰腺肿瘤的关键相互作用和途径。此外，GO 富集和 KEGG 途径分析显示，MAPK 信号和 RTK 途径等重要途径富含 PEE 靶向的基因。此外，对药物相似性和 ADME 特性的评估表明，鞣花酸具有药物样特性，具有很高的口服吸收潜力。总之，PEE 在降低幽门螺杆菌负荷和改善胰腺组织健康方面表现出显著的治疗潜力，同时影响与胰腺肿瘤相关的关键分子标志物和途径。
