Tabaa Manar M El, Harty Mohammed E El, Mohsen Mohamed, Rashad Eman, Negm Walaa A, Elmorshedy Kadreya, Abu-Risha Sally E
Pharmacology & Environmental Toxicology, Environmental Studies & Research Institute (ESRI), University of Sadat City, Sadat City, Menoufia, Egypt.
Pharmacology & Environmental Toxicology, Environmental Studies & Research Institute (ESRI), University of Sadat City, Sadat City, Menoufia, Egypt.
J Nutr Biochem. 2025 Aug;142:109934. doi: 10.1016/j.jnutbio.2025.109934. Epub 2025 Apr 19.
Sotetsuflavone (SF) is an antioxidant flavonoid derived from the Cycas thouarsii R.Br. plant. Although SF regulates numerous cellular pathways influencing inflammation, its antiinflammatory benefits against gastric ulcers are less well-studied. Hence, it is imperative to thoroughly understand the potential gastroprotective mechanisms of SF. This study aimed to explore the effectiveness of SF against indomethacin (IND)-induced gastric ulcers. Network analysis and molecular docking were used to identify the specific targets and pathways related to SF and stomach ulcers. To validate the in vivo pharmacological action of SF, 36 rats were divided into six groups. Ulcer index (UI), protective percentage (PP), gastric mucosal mediators, oxidant/antioxidant status, and inflammatory markers (MIF, M-CSF, and AIF-1) were assessed. Additionally, the expression of PI3K, Akt, Siah2, SOCS3, JAK2, and STAT3 was determined. Stomach histopathology and immunohistochemistry were done. Network pharmacology detected 46 overlapping targets between SF and stomach ulcers, with HIF1A as the primary target among the top hubs. The network also revealed that JAK/STAT, PI3K/Akt, and HIF-1A signaling are among the top 50 markedly enriched KEGG pathways. Furthermore, docking results confirmed that SF has a strong binding affinity towards SOCS3, JAK2, STAT3, M-CSF (CSF-1), and AIF-1. Therefore, we hypothesized that the JAK2/STAT3 pathway may be primarily responsible for SF antiinflammatory action. Through up-regulating SOCS3, SF altered the PI3K/Akt pathway, mitigating oxidative stress, blocking the outflow of inflammatory mediators, and impeding gastric ulcer development. Overall, SF, by the SOCS3-mediated JAK2/STAT3 suppression, might considerably reduce oxidative stress, inflammation, and ulceration caused by indomethacin in the stomach.
铁树黄酮（SF）是一种从苏铁科植物叉叶苏铁中提取的抗氧化类黄酮。尽管SF可调节众多影响炎症的细胞信号通路，但其对胃溃疡的抗炎作用尚未得到充分研究。因此，深入了解SF潜在的胃保护机制势在必行。本研究旨在探讨SF对吲哚美辛（IND）诱导的胃溃疡的疗效。采用网络分析和分子对接技术来确定与SF和胃溃疡相关的特定靶点和信号通路。为验证SF的体内药理作用，将36只大鼠分为六组。评估溃疡指数（UI）、保护率（PP）、胃黏膜介质、氧化/抗氧化状态以及炎症标志物（MIF、M-CSF和AIF-1）。此外，测定PI3K、Akt、Siah2、SOCS3、JAK2和STAT3的表达。进行胃组织病理学和免疫组织化学检查。网络药理学检测到SF与胃溃疡之间有46个重叠靶点，其中HIF1A是核心枢纽中的主要靶点。该网络还显示，JAK/STAT、PI3K/Akt和HIF-1A信号通路是KEGG通路中显著富集的前50条通路之一。此外，对接结果证实SF对SOCS3、JAK2、STAT3、M-CSF（CSF-1）和AIF-1具有很强的结合亲和力。因此，我们推测JAK2/STAT3信号通路可能是SF抗炎作用的主要原因。通过上调SOCS3，SF改变了PI3K/Akt信号通路，减轻氧化应激，阻断炎症介质的释放，并抑制胃溃疡的发展。总体而言，SF通过SOCS3介导的JAK2/STAT3抑制作用，可能会显著减轻吲哚美辛引起的胃氧化应激、炎症和溃疡。
