Deciphering the potential mechanisms of Alternanthera sessilis red against atherosclerosis by integrating LC-MS/MS method, network pharmacology and molecular docking approaches
Omilla Ragavan, Jian Xin Lim, Muhammad Nazrul Hakim Abdullah, Lai Yen Fong, Vuanghao Lim, Jun Jie Tan, Yoke Keong Yong · Journal of Biologically Active Products from Nature · 2024
Background: The red cultivar of Alternanthera sessilis (ASR), a medicinal weed traditionally consumed by Asians, reduces risk of cardiovascular disease with established athero-protective effects from previous studies. However, the underlying mechanisms of ASR against atherosclerosis remains unknown. Objective: This investigation aims to discover the potential mechanisms of ASR in treating atherosclerosis using network pharmacology and molecular docking. Methods: Phytochemicals of ASR were collected via ultra-high performance liquid chromatography analysis and literature search. Screening of their pharmacokinetic properties aligned with Traditional Chinese Medicine System Pharmacology database’s criteria of oral bioavailability ≥30% and drug-likeness ≥0.18. Subsequently, a network pharmacology approach was developed, encompassing the collection of ASR and atherosclerosis possible targets, establishment of protein-protein interaction (PPI) network, construction of compound-target network, analysis of intersecting gene set and identification of hub genes. Molecular docking validated binding affinities between bioactive compounds and the hub genes. Results: Among 179 compounds identified from ASR, only 4 (Dehydrodieugenol, Luteolin, Quercetin and Xanthosine) emerged as key bioactive compounds meeting the criteria. PPI network between ASR and atherosclerosis targets revealed 192 intersecting genes, from which 4 hub genes were discovered: AKT1, HSP90AA1, SRC and ESR1. Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed lipid and atherosclerosis were among the significantly enriched pathways in the top 10 list. Molecular docking results demonstrated Dehydrodieugenol-ESR1 complex exhibiting the highest binding affinity at −8.56 kcal/mol. Conclusion: Although, this study uncovers probable molecular pathways for atherosclerosis therapy using ASR, experimental validation in vitro and in vivo is necessary to confirm these computational findings.