Department of Biology, Universitas Pelita Harapan, Tangerang, 15811, Indonesia.
Center of Excellence Applied Science Academy, Sekolah Pelita Harapan Lippo Village, Tangerang, 15810, Indonesia.
Sci Rep. 2024 Jun 14;14(1):13799. doi: 10.1038/s41598-024-64160-y.
Cardiovascular diseases (CVDs), mainly caused by thrombosis complications, are the leading cause of mortality worldwide, making the development of alternative treatments highly desirable. In this study, the thrombolytic potential of green kiwifruit (Actinidia deliciosa cultivar Hayward) was assessed using in-vitro and in-silico approaches. The crude green kiwifruit extract demonstrated the ability to reduce blood clots significantly by 73.0 ± 1.12% (P < 0.01) within 6 h, with rapid degradation of Aα and Bβ fibrin chains followed by the γ chain in fibrinolytic assays. Molecular docking revealed six favorable conformations for the kiwifruit enzyme actinidin (ADHact) and fibrin chains, supported by spontaneous binding energies and distances. Moreover, molecular dynamics simulation confirmed the binding stability of the complexes of these conformations, as indicated by the stable binding affinity, high number of hydrogen bonds, and consistent distances between the catalytic residue Cys25 of ADHact and the peptide bond. The better overall binding affinity of ADHact to fibrin chains Aα and Bβ may contribute to their faster degradation, supporting the fibrinolytic results. In conclusion, this study demonstrated the thrombolytic potential of the green kiwifruit-derived enzyme and highlighted its potential role as a natural plant-based prophylactic and therapeutic agent for CVDs.
心血管疾病（CVDs）主要由血栓并发症引起，是全球范围内导致死亡的主要原因，因此非常需要开发替代治疗方法。本研究采用体外和计算方法评估了绿奇异果（Actinidia deliciosa 品种 Hayward）的溶栓潜力。粗绿奇异果提取物在 6 小时内可显著降低 73.0±1.12%（P<0.01）的血栓，纤维蛋白溶解试验中 Aα 和 Bβ 纤维蛋白链迅速降解，随后是γ链。分子对接显示奇异果酶 actinidin（ADHact）和纤维蛋白链有六个有利构象，这得到了自发结合能和距离的支持。此外，分子动力学模拟证实了这些构象的复合物具有结合稳定性，这表现为结合亲和力稳定、氢键数量多以及 ADHact 的催化残基 Cys25 与肽键之间的距离一致。ADHact 对纤维蛋白链 Aα 和 Bβ 的整体结合亲和力更好，可能有助于它们更快地降解，这支持了纤维蛋白溶解的结果。总之，本研究证明了绿奇异果来源的酶具有溶栓潜力，并强调了其作为 CVDs 天然植物性预防和治疗剂的潜在作用。
