Wargasetia Teresa Liliana, Ratnawati Hana, Widodo Nashi, Widyananda Muhammad Hermawan
Faculty of Medicine, Universitas Kristen Maranatha (Maranatha Christian University), Bandung, Indonesia.
Biology Department, Faculty of Mathematics and Natural Sciences, University of Brawijaya, Malang, Indonesia.
Bioinform Biol Insights. 2023 Jan 16;17:11779322221149613. doi: 10.1177/11779322221149613. eCollection 2023.
Oxidative stress and inflammation have a role in the development of various diseases. Oxidative stress and inflammation are associated with many proteins, including Kelch ECH associating protein 1 (KEAP1) and inducible nitric oxide synthase (iNOS) proteins. The active compounds contained in have antioxidant and anti-inflammatory properties. This study aimed to evaluate the antioxidant and anti-inflammatory activity of sea cucumber's active compounds by targeting KEAP1 and iNOS proteins. 2,2-Diphenyl-1-picrylhydrazyl (DPPH) and nitric oxide (NO) scavenging activity of extract were measured spectrophotometrically. The 3-dimensional (3D) structures of sea cucumber's active compounds and proteins were obtained from the PubChem and Research Collaboratory for Structural Bioinformatics Protein Data Bank (RCSB PDB) databases. Molecular docking was performed using AutoDock Vina software. Molecular dynamics simulations were carried out using Yet Another Scientific Artificial Reality Application (YASARA) software with environmental parameters according to the cell's physiological conditions. The membrane permeability test was performed using the PerMM web server. The methanol extract of had a weak antioxidant activity against DPPH and strong activity against NO radical. Scabraside and holothurinoside G had the most negative binding affinity values when interacting with the active site of KEAP1 and iNOS proteins. Molecular dynamics simulations also showed that both compounds were stable when interacting with KEAP1 and iNOS. However, scabraside and holothurinoside G were difficult to penetrate the cell plasma membrane, which is seen from the high energy transfer value in the lipid acyl chain region of phospholipids. Scabraside and holothurinoside G are predicted to act as antioxidants and anti-inflammations, but in their implementation to and study, it is necessary to have liposomes or nanoparticles, or other delivery methods to help these 2 compounds enter the cell.
氧化应激和炎症在多种疾病的发展过程中起作用。氧化应激和炎症与许多蛋白质有关，包括 Kelch 样 ECH 相关蛋白 1（KEAP1）和诱导型一氧化氮合酶（iNOS）蛋白。[海参名称未给出]中含有的活性化合物具有抗氧化和抗炎特性。本研究旨在通过靶向 KEAP1 和 iNOS 蛋白来评估海参活性化合物的抗氧化和抗炎活性。采用分光光度法测定了[海参名称未给出]提取物的 2,2 - 二苯基 - 1 - 苦基肼（DPPH）和一氧化氮（NO）清除活性。海参活性化合物和蛋白质的三维（3D）结构分别从 PubChem 和结构生物信息学蛋白质数据库（RCSB PDB）中获取。使用 AutoDock Vina 软件进行分子对接。根据细胞生理条件，使用 Yet Another Scientific Artificial Reality Application（YASARA）软件进行分子动力学模拟，并设置环境参数。使用 PerMM 网络服务器进行膜通透性测试。[海参名称未给出]的甲醇提取物对 DPPH 具有较弱的抗氧化活性，对 NO 自由基具有较强的活性。当与 KEAP1 和 iNOS 蛋白的活性位点相互作用时，海参皂苷和海参环肽 G 具有最负的结合亲和力值。分子动力学模拟还表明，这两种化合物与 KEAP1 和 iNOS 相互作用时是稳定的。然而，从磷脂脂质酰链区域的高能量转移值可以看出，海参皂苷和海参环肽 G 难以穿透细胞质膜。预计海参皂苷和海参环肽 G 具有抗氧化和抗炎作用，但在将其应用于[海参名称未给出]和[研究名称未给出]研究时，有必要使用脂质体或纳米颗粒或其他递送方法来帮助这两种化合物进入细胞。
