基于网络药理学探究半枝莲治疗糖尿病性胃癌的活性成分及其作用机制

Exploring the active ingredients of Banzhilian and its mechanism of action on diabetic Gastric cancer based on network pharmacology.

作者信息

Cao Haikun, Song Hui, Zhou Weiguo, Lv Xiaohu, Liu Xinlei, Xiang Zheng, Fu Rui, Cheng Yixian, Chen Junjie, Wang Shengwei, Hu Yvbo, Yan Huayue, You Wenlong, Guo Changqian, Chen Bo, Cao Guodong, Wang Wei, Jia Jianguang

机构信息

Department of Surgical Oncology, First Affiliated Hospital of Bengbu Medical University, 801 Zhihuai Road, Longzihu District, Bengbu City, 233000, Anhui Province, People's Republic of China.

Department of Surgical Oncology, Second Affiliated Hospital of Bengbu Medical University, No. 633, Longhua Road, Huaishang District, Bengbu City, 233000, Anhui Province, People's Republic of China.

出版信息

Sci Rep. 2025 Apr 28;15(1):14808. doi: 10.1038/s41598-025-98214-6.

Abstract

The incidence of Gastric cancer (GC) has shown a sharp upward trend, and patients with GC complicated by diabetes exhibit significantly worse clinical outcomes and prognosis compared to those without diabetes. Traditional Chinese medicine has played a crucial role in the treatment of both GC and diabetes. Currently, Banzhilian(Scutellaria barbata D. Don) is utilized in the treatment of GC; however, the specific small-molecule monomers it contains and their mechanisms of action have not yet been fully elucidated. This study aims to explore the mechanism of quercetin, a key component of Banzhilian, through network pharmacology, molecular docking, molecular dynamics (MD) simulation, bioinformatics, and in vitro and in vivo experiments. Initially, core targets and key pathways involved in the treatment of diabetes-associated GC (GC-diabetes) were identified using public databases. Subsequently, molecular docking, MD simulation, and survival analysis were performed. Experimental validation included CCK-8 assays, colony formation assays, apoptosis detection, cell cycle analysis, wound healing assays, Transwell migration assays, Western blotting, and mouse subcutaneous tumor formation experiments to evaluate the effects of quercetin, as an active monomer in Banzhilian, on Gastric cancer cells (HGC-27-HG cells) under high-glucose conditions. In this study, quercetin was identified as the key active component, with AKT1, TP53, JUN, MYC, and CCND1 recognized as the target genes, and the PI3K/AKT signaling pathway as the primary regulatory pathway. The results of the study indicate that the proliferation, migration, and invasion capabilities of HGC-27-HG cells are significantly higher than those of HGC-27 cells. However, quercetin inhibited the growth of HGC-27-HG cells, promoted apoptosis, induced cell cycle arrest at the G0/G1 phase, and reduced the cells' migration and invasion abilities. Furthermore, it downregulated the expression of target genes and their phosphorylation levels. The experimental findings confirmed that quercetin, as an active monomer in Banzhilian, suppresses the proliferation of HGC-27-HG cells by inhibiting the PI3K/AKT/MYC pathway, promoting apoptosis, blocking cell cycle progression, and inhibiting cell migration and invasion.

摘要

胃癌(GC)的发病率呈急剧上升趋势,与未患糖尿病的GC患者相比,合并糖尿病的GC患者临床结局和预后明显更差。中医在GC和糖尿病的治疗中都发挥了关键作用。目前,半枝莲(Scutellaria barbata D. Don)被用于GC的治疗;然而,其所含的具体小分子单体及其作用机制尚未完全阐明。本研究旨在通过网络药理学、分子对接、分子动力学(MD)模拟、生物信息学以及体外和体内实验,探索半枝莲的关键成分槲皮素的作用机制。首先,利用公共数据库确定与糖尿病相关的GC(GC-糖尿病)治疗中涉及的核心靶点和关键途径。随后,进行分子对接、MD模拟和生存分析。实验验证包括CCK-8测定、集落形成测定、凋亡检测、细胞周期分析、伤口愈合测定、Transwell迁移测定、蛋白质免疫印迹法以及小鼠皮下肿瘤形成实验,以评估作为半枝莲中活性单体的槲皮素在高糖条件下对胃癌细胞(HGC-27-HG细胞)的影响。在本研究中,槲皮素被确定为关键活性成分,AKT1、TP53、JUN、MYC和CCND1被识别为靶基因,PI3K/AKT信号通路为主要调控途径。研究结果表明,HGC-27-HG细胞的增殖、迁移和侵袭能力明显高于HGC-27细胞。然而,槲皮素抑制了HGC-27-HG细胞的生长,促进了凋亡,诱导细胞周期停滞在G0/G1期,并降低了细胞的迁移和侵袭能力。此外,它下调了靶基因的表达及其磷酸化水平。实验结果证实,作为半枝莲中活性单体的槲皮素通过抑制PI3K/AKT/MYC途径、促进凋亡、阻断细胞周期进程以及抑制细胞迁移和侵袭来抑制HGC-27-HG细胞的增殖。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3de3/12037812/9a27b70925af/41598_2025_98214_Fig1_HTML.jpg

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