Xia Juan, Hu Jun-Nan, Wang Zi, Cai En-Bo, Ren Shen, Wang Ying-Ping, Lei Xiu-Juan, Li Wei
Institute of Special Animal and Plant Sciences of Chinese Academy of Agricultural Sciences, Changchun, China.
College of Life Sciences, Jilin Agricultural University, Changchun, China.
Front Pharmacol. 2022 Oct 12;13:1040504. doi: 10.3389/fphar.2022.1040504. eCollection 2022.
Epimedii Folium, as a natural botanical medicine, has been reported to have protective effects on intestinal diseases by modulating multiple signaling pathways. This study aimed to explore the potential targets and molecular mechanisms of Epimedii Folium extract (EFE) against cisplatin-induced intestinal injury through network pharmacology, molecular docking, and animal experiments. Network pharmacology was used to predict potential candidate targets and related signaling pathways. Molecular docking was used to simulate the interactions between significant potential candidate targets and active components. For experimental validation, mice were intraperitoneally injected with cisplatin 20 mg/kg to establish an intestinal injury model. EFE (100, 200 mg/kg) was administered to mice by gavage for 10 days. The protective effect of EFE on intestinal injury was analyzed through biochemical index detection, histopathological staining, and western blotting. Network pharmacology analysis revealed that PI3K-Akt and apoptosis signaling pathways were thought to play critical roles in EFE treatment of the intestinal injury. Molecular docking results showed that the active constituents of Epimedii Folium, including Icariin, Epimedin A, Epimedin B, and Epimedin C, stably docked with the core AKT1, p53, TNF-α, and NF-κB. In verified experiments, EFE could protect the antioxidant defense system by increasing the levels of glutathione peroxidase (GSH-Px) and catalase (CAT) while reducing the content of malondialdehyde (MDA). EFE could also inhibit the expression of NF-κB and the secretion of inflammatory factors, including TNF-α, IL-1β, and IL-6, thereby relieving the inflammatory damage. Further mechanism studies confirmed that EFE had an excellent protective effect on cisplatin-induced intestinal injury by regulating PI3K-Akt, caspase, and NF-κB signaling pathways. In summary, EFE could mitigate cisplatin-induced intestinal damage by modulating oxidative stress, inflammation, and apoptosis.
淫羊藿作为一种天然植物药，已有报道称其可通过调节多种信号通路对肠道疾病起到保护作用。本研究旨在通过网络药理学、分子对接和动物实验，探索淫羊藿提取物（EFE）对顺铂诱导的肠道损伤的潜在靶点及分子机制。利用网络药理学预测潜在的候选靶点和相关信号通路，运用分子对接模拟重要潜在候选靶点与活性成分之间的相互作用。为进行实验验证，给小鼠腹腔注射20mg/kg顺铂以建立肠道损伤模型，通过灌胃给予小鼠EFE（100、200mg/kg），持续10天。通过生化指标检测、组织病理学染色和蛋白质印迹法分析EFE对肠道损伤的保护作用。网络药理学分析表明，PI3K-Akt和凋亡信号通路在EFE治疗肠道损伤中起关键作用。分子对接结果显示，淫羊藿的活性成分，包括淫羊藿苷、朝藿定A、朝藿定B和朝藿定C，与核心AKT1、p5蛋白、TNF-α和NF-κB稳定对接。在验证实验中，EFE可通过提高谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶（CAT）水平同时降低丙二醛（MDA）含量来保护抗氧化防御系统。EFE还可抑制NF-κB的表达以及包括TNF-α、IL-1β和IL-6在内的炎症因子的分泌，从而减轻炎症损伤。进一步的机制研究证实，EFE通过调节PI3K-Akt、半胱天冬酶和NF-κB信号通路对顺铂诱导的肠道损伤具有良好的保护作用。总之，EFE可通过调节氧化应激、炎症和凋亡来减轻顺铂诱导的肠道损伤。
