Institute for Liver and Digestive Diseases, College of Medicine, Hallym University, Chuncheon, Korea.
Clin Transl Sci. 2024 Mar;17(3):e13778. doi: 10.1111/cts.13778.
Persea americana fruit (PAF) is a favorable nutraceutical resource that comprises diverse unsaturated fatty acids (UFAs). UFAs are significant dietary supplementation, as they relieve metabolic disorders, including obesity (OB). In another aspect, this study was focused on the anti-OB efficacy of the non-fatty acids (NFAs) in PAF through network pharmacology (NP). Natural product activity & species source (NPASS), SwissADME, similarity ensemble approach (SEA), Swiss target prediction (STP), DisGeNET, and online Mendelian inheritance in man (OMIM) were utilized to gather significant molecules and its targets. The crucial targets were adopted to construct certain networks: protein-protein interaction (PPI), PAF-signaling pathways-targets-compounds (PSTC) networks, a bubble chart, molecular docking assay (MDA), and density function theory (DFT). Finally, the toxicities of the key compounds were validated by ADMETlab 2.0 platform. All 41 compounds in PAF conformed to Lipinski's rule, and the key 31 targets were identified between OB and PAF. On the bubble chart, PPAR signaling pathway had the highest rich factor, suggesting that the pathway might be an agonism for anti-OB. Conversely, estrogen signaling pathway had the lowest rich factor, indicating that the mechanism might be antagonism against OB. Likewise, the PSTC network represented that AKT1 had the greatest degree value. The MDA results showed that AKT1-gamma-tocopherol, PPARA-fucosterol, PPARD-stigmasterol, (PPARG)-fucosterol, (NR1H3)-campesterol, and ILK-alpha-tocopherol formed the most stable conformers. The DFT represented that the five molecules might be promising agents via multicomponent targeting. Overall, this study suggests that the NFAs in PAF might play important roles against OB.
鳄梨（Persea americana fruit，PAF）是一种有利的营养保健品，其富含多种不饱和脂肪酸（Unsaturated fatty acids，UFAs）。UFAs 是重要的膳食补充剂，因为它们可以缓解代谢紊乱，包括肥胖症（Obesity，OB）。在另一方面，本研究通过网络药理学（Network pharmacology，NP）聚焦于 PAF 中非脂类成分（Non-fatty acids，NFAs）的抗 OB 功效。利用天然产物活性和物种来源（Natural product activity & species source，NPASS）、瑞士药物代谢（SwissADME）、相似性集成方法（Similarity Ensemble Approach，SEA）、瑞士靶点预测（Swiss target prediction，STP）、疾病基因（DisGeNET）和在线孟德尔遗传数据库（Online Mendelian Inheritance in Man，OMIM）收集了重要的分子及其靶点。采用关键靶点构建了特定网络：蛋白-蛋白相互作用（Protein-protein interaction，PPI）网络、PAF 信号通路-靶点-化合物（PAF-signaling pathways-targets-compounds，PSTC）网络、气泡图、分子对接试验（Molecular docking assay，MDA）和密度泛函理论（Density functional theory，DFT）。最后，利用 ADMETlab 2.0 平台验证了关键化合物的毒性。PAF 中的 41 种化合物均符合 Lipinski 规则，OB 与 PAF 之间确定了 31 个关键靶点。在气泡图中，过氧化物酶体增殖物激活受体信号通路（PPAR signaling pathway）的富集因子最高，提示该通路可能是抗 OB 的激动剂。相反，雌激素信号通路（Estrogen signaling pathway）的富集因子最低，提示该机制可能是 OB 的拮抗剂。同样，PSTC 网络显示 AKT1 具有最大的度数值。MDA 结果表明，AKT1-γ-生育酚、PPARA-岩藻甾醇、PPARD-豆甾醇、（PPARG）-岩藻甾醇、（NR1H3）-菜油甾醇和 ILK-α-生育酚形成最稳定的构象。DFT 表明，这 5 种分子可能是多成分靶向的潜在药物。总体而言，本研究提示 PAF 中的 NFAs 可能在抗 OB 方面发挥重要作用。
