Work

Exploring the anti-obesity potential of Ailanthus excelsa Roxb in vitro enzymatic inhibition and computational pharmacology insights

Year: 2025

Type: article

Abstract: This study explores the potential of Ailanthus excelsa Roxb. for managing obesity by evaluating its effects on key metabolic enzymes. We evaluated a hydroalcoholic extract and its fractions for their ability to modulate important metabolic enzymes, porcine pancreatic lipase , HMG-CoA reductase , α-glucosidase , and α-amylase activities. Our methodology integrated in vitro enzymatic assays with cluster analysis (MCODE, ClueGO, and Cluepedia) and network pharmacology to elucidate interactions between metabolites and target enzymes. Protein-protein interaction (PPI) analysis, consisting of a network with 51 nodes and 264 edges, was performed using the CytoNCA plugin to calculate topological parameters. Key targets were identified based on degree centrality, including ADIPOQ , PPARA , PPARG , IL6 , TNF , and AKT1 . Cluster analysis of the PPI networks, conducted using the MCODE plugin, highlighted a top cluster with a high score of 22.82. Network pharmacology has identified key targets associated with obesity, including HK1 , HK2 , PIK3CA , AKT1 , MTOR , CD36 , ACACB , SLC2A4 , CPTIA , INSR , ACACA , FASN , and ADIPOQ . These targets are linked to highly modulated metabolic pathways. Isoquercetin shows significant binding affinities: − 7.11 for HMG-CoA Reductase (PDB ID: 1HW9), -9.96 for lipase (PDB ID: 1LPB), − 8.96 for α-amylase , and − 10.41 for α-Glucosidase (PDB ID: 3A47). The ethyl acetate fractions exhibit notable inhibition of Porcine Pancreatic lipase (IC 50 : 56.25 ± 4.85 µg/mL) and HMG-CoA reductase (IC 50 : 108.27 ± 3.38 µg/mL), α-glucosidase (IC 50 : 117.08 ± 3.28 µg/mL), and α-amylase (IC 50 : 125.93 ± 2.29 µg/mL). Moreover, metabolites showed stronger binding affinities to all four enzymes than reference molecules. By integrating in vitro assays with molecular modeling , this study highlights the promising potential of A. excelsa and its fractions in obesity management, offering valuable insights into its therapeutic applications.

Source: Scientific Reports

DOI: 10.1038/s41598-025-14420-2