Kamaria Priyanka, Tiwari Priyanka, Prabhakaran Prabitha, Bhardwaj Sakshi, Kolachi Krishna, Thapa Shankar
Department of Pharmaceutical Chemistry KLE College of Pharmacy, Bengaluru, KLE Academy of Higher Education and Research Belagavi Karnataka India.
Department of Pharmaceutical Chemistry JSS College of Pharmacy Mysuru Karnataka India.
Food Sci Nutr. 2025 Sep 8;13(9):e70857. doi: 10.1002/fsn3.70857. eCollection 2025 Sep.
Oral cancer (OC) remains a significant global health concern due to its high incidence and mortality. (QI), a traditional medicinal plant, harbors bioactive compounds with potential anticancer properties. This study systematically integrates multiple computational and experimental approaches to identify and validate the anticancer potential of QI phytoconstituents. Network pharmacology was used to predict key molecular targets and signaling pathways, notably apoptosis and the PI3K-Akt pathway-providing mechanistic validation through pathway-level insights into anticancer activity. Molecular docking revealed strong binding affinities of Nyctanthic acid (-125.426 and -113.841 kcal/mol) and β-Glucogallin (-96.7558 and -112.534 kcal/mol) with AKT1 and GAPDH, respectively. Molecular dynamics (MD) simulations further confirmed the structural validation by demonstrating the stability and conformational integrity of these protein-ligand complexes. Cellular validation was achieved through cytotoxic assay on KB oral cancer cells, which showed dose-dependent cytotoxicity, with IC values of 224.41 ± 2.01 μg/mL for the QI extract and 213.77 ± 1.98 μg/mL for Cisplatin. Density Functional Theory (DFT) analysis further supported the electronic stability and reactivity of Nyctanthic acid. From the study, Nyctanthic acid showed the superior binding affinity, target relevance (AKT1), and computational stability that make it a promising multi-target anticancer candidate. These findings lay the groundwork for future in vivo studies, formulation development, and translational drug development.
口腔癌（OC）因其高发病率和死亡率仍然是一个重大的全球健康问题。七叶一枝花（QI），一种传统药用植物，含有具有潜在抗癌特性的生物活性化合物。本研究系统地整合了多种计算和实验方法，以识别和验证QI植物成分的抗癌潜力。网络药理学用于预测关键分子靶点和信号通路，特别是凋亡和PI3K-Akt通路，通过对抗癌活性的通路水平洞察提供机制验证。分子对接显示，夜花酸（-125.426和-113.841 kcal/mol）和β-葡萄糖没食子酸酯（-96.7558和-112.534 kcal/mol）分别与AKT1和GAPDH具有很强的结合亲和力。分子动力学（MD）模拟通过证明这些蛋白质-配体复合物的稳定性和构象完整性进一步证实了结构验证。通过对KB口腔癌细胞的细胞毒性试验实现了细胞验证，该试验显示出剂量依赖性细胞毒性，QI提取物的IC值为224.41±2.01μg/mL，顺铂的IC值为213.77±1.98μg/mL。密度泛函理论（DFT）分析进一步支持了夜花酸的电子稳定性和反应活性。从研究中可以看出，夜花酸显示出优异的结合亲和力、靶点相关性（AKT1）和计算稳定性，使其成为一个有前途的多靶点抗癌候选物。这些发现为未来的体内研究、制剂开发和转化药物开发奠定了基础。
