Hasan Md Imran, Islam Kh Mujahidul, Hasan Md Nahid, Rahman Md Mizanur, Rahman Md Habibur, Moon Seungjoon, Park Moon Nyeo, Kang Han Na, Kim Bonglee
Department of Life Science, Texas A& M University San Antonio, Texas, USA.
Department of Computer Science and Engineering, Islamic University, Kushtia, 7003, Bangladesh.
Curr Pharm Des. 2025 Mar 26. doi: 10.2174/0113816128356225250305081937.
Pancreatic cancer (PC) remains a formidable challenge in cancer, which requires innovative approaches to identify novel therapeutic strategies. Evodia rutaecarpa, a traditional herbal remedy known for its analgesic and antiemetic properties, has been reported to exhibit anticancer effects.
We employed network pharmacology to elucidate the bioactive ingredients of Evodia rutaecarpa and their potential targets in the context of early-onset pancreatic cancer. By integrating data from public databases, we identified genes associated with PC and developed a protein-protein interaction (PPI) network. Topological analysis of the PPI network facilitated the identification of core targets, which were subsequently subjected to molecular docking with corresponding bioactive ingredients of Evodia rutaecarpa. The computational approach aimed to unveil the pharmacological mechanisms of basic putative crucial proteins and associated pathways implicated in early-onset PC. Pathway and GO analysis highlighted the significant involvement of Evodia rutaecarpa in pathways such as cAMP signaling, cytokine-cytokine receptor interaction, rheumatoid arthritis, interleukin signaling, bladder cancer, IL-17, IL-24 signaling, cytokine-mediated signaling, chemokine, and calcium-mediated signaling.
Further exploration focused on a hub protein module derived from PPIs, with molecular docking emphasizing strong binding interactions between Evodia rutaecarpa and ERBB2, a protein strongly implicated in PC management compared to other identified hub proteins (STAT1, ERBB2, CXCL10, INS, RACK1, FOS, HLA-DRB1, POMC, PRKAA1). Additionally, the pharmacokinetic analysis of Evodia rutaecarpa indicated its efficacy as a therapeutic agent with minimal adverse effects. Rutaecarpine, identified as the main bioactive ingredient, emerged as a potential inhibitor of PC growth through the suppression of ERBB2.
These outcomes provide novel insights into the prevention and treatment of PC, presenting Evodia rutaecarpa as a promising candidate for further experimental validation and clinical exploration. The identified discovery has the potential to reduce the drug resistance of Evodia rutaecarpa by engaging with a new target in a specific manner, thus improving therapeutic effectiveness.
胰腺癌（PC）仍然是癌症领域的一项艰巨挑战，这需要创新方法来确定新的治疗策略。吴茱萸是一种以其止痛和止吐特性而闻名的传统草药，据报道具有抗癌作用。
我们采用网络药理学来阐明吴茱萸的生物活性成分及其在早发性胰腺癌背景下的潜在靶点。通过整合来自公共数据库的数据，我们确定了与胰腺癌相关的基因，并构建了蛋白质-蛋白质相互作用（PPI）网络。对PPI网络进行拓扑分析有助于识别核心靶点，随后将这些靶点与吴茱萸相应的生物活性成分进行分子对接。该计算方法旨在揭示早发性胰腺癌中基本假定关键蛋白和相关通路的药理机制。通路和基因本体（GO）分析突出了吴茱萸在诸如环磷酸腺苷（cAMP）信号传导、细胞因子-细胞因子受体相互作用、类风湿性关节炎、白细胞介素信号传导、膀胱癌、白细胞介素-17（IL-17）、白细胞介素-24（IL-24）信号传导、细胞因子介导的信号传导、趋化因子以及钙介导的信号传导等通路中的重要参与。
进一步的探索聚焦于从PPI中衍生出的一个枢纽蛋白模块，分子对接强调了吴茱萸与表皮生长因子受体2（ERBB2）之间的强结合相互作用，与其他已识别的枢纽蛋白（信号转导和转录激活因子1（STAT1）、ERBB2、趋化因子配体10（CXCL10）、胰岛素（INS）、活化C激酶1受体（RACK1）、原癌基因FOS、人白细胞抗原DRB1（HLA-DRB1）、阿片促黑皮质素（POMC）、蛋白激酶A催化亚基α（PRKAA1））相比，ERBB2在胰腺癌治疗中具有更强的相关性。此外，吴茱萸的药代动力学分析表明其作为一种治疗药物具有疗效且副作用最小。被确定为主要生物活性成分的吴茱萸次碱，通过抑制ERBB2成为胰腺癌生长的潜在抑制剂。
这些结果为胰腺癌的预防和治疗提供了新的见解，表明吴茱萸是进一步实验验证和临床探索的有希望的候选药物。所确定的发现有可能通过以特定方式作用于新靶点来降低吴茱萸的耐药性，从而提高治疗效果。
