Abstract

In current study, we studied the phytochemicals of Cullen corylifolium (fruits) in which we identify twenty compounds, including two coumarins (1 and 2), three coumestans (3–5), fourchalcone (6–9), three dihydroflavones (10–12), four isoflavones (13–16), one flavonoid (17) and three meroterpenes (18–20). Among these, compounds 4, 5 and 12 were isolated from C. corylifolium for the first time. The ferroptosis inhibitory effects of the isolated phytochemicals were assessed using erastin-exposed HT22 mouse hippocampal cells. Compounds 3 and 18 showed the most potent inhibition with the IC₅₀ values of 5.21 μM and 5.41 μM, respectively. Moreover, molecular docking study showed that compound 3 possessed tremendous inhibitory affinity for human 5-lipoxygenase (5-LOX) and Kelch-like ECH-related protein 1: nuclear factor erythroid 2-related factor 2 (Keap1-Nrf2) protein-protein interactions, two important ferroptosis-related targets. These findings indicate that compound 3 (psoralidin) may be a potential therapeutic agent for the treatment of ferroptosis-related diseases.

摘要

在目前的研究中，我们研究了Cullen corylifolium（水果）的植物化学物质，我们在其中确定了 20 种化合物，包括两种香豆素（1和2）、三种香豆素（3 – 5）、四查耳酮（6 – 9）、三种二氢黄酮（10 – 12 )、四种异黄酮 ( 13 – 16 )、一种类黄酮 ( 17 ) 和三种萜烯 ( 18 – 20 )。在这些当中，化合物4，5和12是从分离C. corylifolium首次。使用erastin 暴露的HT22 小鼠海马细胞评估分离的植物化学物质的铁死亡抑制作用。化合物3和18显示出最有效的抑制作用，IC ₅₀值分别为 5.21 μM 和 5.41 μM。此外，分子对接研究表明，化合物3对人5-脂氧合酶（5-LOX）和Kelch样ECH相关蛋白1：核因子红细胞2相关因子2（Keap1-Nrf2）蛋白-蛋白相互作用具有巨大的抑制亲和力，两个重要的铁死亡相关目标。这些发现表明，化合物3（补骨脂素）可能是治疗铁死亡相关疾病的潜在治疗剂。