Majhi Rita, Kurmi Sagar, Tayara Hilal, Chong Kil To
Department of Electronics and Information Engineering, Jeonbuk National University, Jeonju-si 54896, Jeollabuk-do, Republic of Korea.
School of International Engineering and Science, Jeonbuk National University, Jeonju-si 54896, Jeollabuk-do, Republic of Korea.
Pharmaceuticals (Basel). 2025 Jun 15;18(6):896. doi: 10.3390/ph18060896.
: Pomegranate peel, often discarded as waste, contains abundant bioactive compounds such as polyphenols, vitamins, flavonoids, tannins, anthocyanins, and many more. This contributes to remarkable bioactivities, including anticancer, anti-inflammatory, antioxidant, antibacterial, and antifungal properties. Pancreatic cancer is a deadly cancer with a 9% survival rate. Its aggressiveness, invasiveness, quick metastasis, and poor prognosis significantly decrease the survival rate. Thus, we aim to explore pomegranate peel as a possible alternative medication for treating pancreatic cancer through virtual methods. : Firstly, bioactive compounds were collected from multiple databases and screened for oral bioavailability (OB) ≥ 0.3 and drug likeness (DL) ≥ 0.18 scores. Simultaneously, network pharmacology was employed to extract the most probable targets for pancreatic cancer. Further computational analyses were performed, including molecular docking, molecular dynamics simulation, and in silico pharmacokinetics evaluation. : Consequently, the top 10 key targets from network analysis were AKT1, IL6, TNF, SRC, STAT3, EGFR, BCL2, HSP90AA1, HIF1A, and PTGS2. However, only AKT1, EGFR, BCL2, HSP90AA1, and PTGS2 exhibited strong binding affinities with pomegranate compounds, which are significantly declared in affected cells to enhance cancer progression. Outcomes from molecular dynamics simulations, particularly RMSD, RMSF, hydrogen bonding, and radius of gyration (Rg), confirmed stable interactions between 1-O-Galloyl-beta-D-glucose, epicatechin, phloridzin, and epicatechin gallate with respective target proteins. : This suggests that pomegranate peels hold anticancer bioactive compounds for treating pancreatic cancer. Surprisingly, most compounds adhere to Lipinski's and Pfizer's rules and display no toxicity. However, as this study relies entirely on computational methods, experimental validation is necessary to confirm these findings and assess real-world efficacy and potential side effects.
石榴皮常被当作废物丢弃，但其含有丰富的生物活性化合物，如多酚、维生素、黄酮类化合物、单宁、花青素等等。这赋予了石榴皮显著的生物活性，包括抗癌、抗炎、抗氧化、抗菌和抗真菌特性。胰腺癌是一种致命的癌症，生存率仅为9%。其侵袭性、转移性强、转移速度快且预后差，显著降低了生存率。因此，我们旨在通过虚拟方法探索石榴皮作为治疗胰腺癌的一种可能替代药物。首先，从多个数据库收集生物活性化合物，并筛选口服生物利用度（OB）≥0.3且类药性（DL）≥0.18的评分。同时，采用网络药理学方法提取胰腺癌最可能的靶点。进一步进行了包括分子对接、分子动力学模拟和计算机模拟药代动力学评估在内的计算分析。结果，网络分析得出的前10个关键靶点为AKT1、IL6、TNF、SRC、STAT3、EGFR、BCL2、HSP90AA1、HIF1A和PTGS2。然而，只有AKT1、EGFR、BCL2、HSP90AA1和PTGS2与石榴化合物表现出强结合亲和力，这些靶点在受影响细胞中显著促进癌症进展。分子动力学模拟的结果，特别是均方根偏差（RMSD）、均方根波动（RMSF）、氢键和回转半径（Rg），证实了1-O-没食子酰基-β-D-葡萄糖、表儿茶素、根皮苷和表儿茶素没食子酸酯与各自靶蛋白之间的稳定相互作用。这表明石榴皮含有治疗胰腺癌的抗癌生物活性化合物。令人惊讶的是，大多数化合物符合Lipinski规则和辉瑞规则，且无毒性。然而，由于本研究完全依赖计算方法，因此需要进行实验验证以证实这些发现，并评估实际疗效和潜在副作用。
