Sailah Illah, Tallei Trina E, Safitri Linda, Tamala Yulianida, Halimatushadyah Ernie, Ekatanti Dewi, Maulydia Nur B, Celik Ismail
Agroindustrial Engineering Study Program, Department of Agroindustrial Technology, Faculty of Agricultural Engineering and Technology, Institut Pertanian Bogor, Bogor, Indonesia.
Department of Biology, Faculty of Mathematics and Natural Sciences, Universitas Sam Ratulangi, Manado, Indonesia.
Narra J. 2024 Dec;4(3):e1016. doi: 10.52225/narra.v4i3.1016. Epub 2024 Oct 7.
The therapeutic potential of bitter leaf ( Del.) has been established both empirically and in various scientific investigations. However, the molecular pathways related to its possible anti-inflammatory and antioxidant properties remain unclear. Therefore, the aim of this study was to elucidate the molecular interactions between bitter leaf's bioactive compounds and cellular targets involved in these activities. The compounds in bitter leaf were identified using gas chromatography-mass spectrometry (GC-MS) analysis, and subsequently, a network pharmacology approach was employed together with molecular docking and dynamics simulations. Acetonitrile (4.5%) and dimethylamine (4.972%) were the most prevalent compounds among the 38 identified by the GC-MS analysis of bitter leaf extract. The proto-oncogene tyrosine-protein kinase (SRC) demonstrated significant connectivity within the antioxidant network, highlighting its pivotal role in facilitating inter-protein communication. It also exhibited strategic positioning in anti-inflammatory mechanisms based on closeness centrality (0.385). The enrichment analysis suggested multifaceted mechanisms of bitter leaf compounds, including transcriptional regulation and diverse cellular targeting, indicating broad antioxidant and anti-inflammatory effects. Eicosapentaenoyl ethanolamide (EPEA) displayed strong interactions with multiple proteins, including SRC (-7.17 kcal/mol) and CYPA (-6.88 kcal/mol). Moreover, EPEA demonstrated to form a stable interaction with SRC during a 100 ns simulation. In conclusion, the computational simulations revealed that the hypothetical antioxidant and anti-inflammatory actions of bitter leaf compounds were achieved by specifically targeting SRC. However, confirmation using either in vitro or in vivo techniques is necessary.
苦叶（Del.）的治疗潜力已通过经验和各种科学研究得到证实。然而，与其可能的抗炎和抗氧化特性相关的分子途径仍不清楚。因此，本研究的目的是阐明苦叶生物活性化合物与参与这些活动的细胞靶点之间的分子相互作用。使用气相色谱 - 质谱（GC-MS）分析鉴定苦叶中的化合物，随后采用网络药理学方法结合分子对接和动力学模拟。乙腈（4.5%）和二甲胺（4.972%）是通过苦叶提取物的GC-MS分析鉴定出的38种化合物中最普遍的化合物。原癌基因酪氨酸蛋白激酶（SRC）在抗氧化网络中显示出显著的连通性，突出了其在促进蛋白质间通讯中的关键作用。基于接近中心性（0.385），它在抗炎机制中也表现出战略定位。富集分析表明苦叶化合物具有多方面的机制，包括转录调控和多种细胞靶向作用，表明其具有广泛的抗氧化和抗炎作用。二十碳五烯酰乙醇酰胺（EPEA）与多种蛋白质表现出强烈相互作用，包括SRC（-7.17 kcal/mol）和CYPA（-6.88 kcal/mol）。此外，在100 ns模拟过程中，EPEA与SRC形成了稳定的相互作用。总之，计算模拟表明苦叶化合物假设的抗氧化和抗炎作用是通过特异性靶向SRC实现的。然而，需要使用体外或体内技术进行证实。
