DOI: 10.6084/m9.figshare.30156154
title: Analysis of the therapeutic potential of astragalin: insights into target interactions and mechanisms

description: Astragalin (AST), a flavonoid, shows promise for neurodegenerative diseases like Parkinson’s disease (PD), cognitive impairment (CI), and depression. However, its efficacy in treating neurodegenerative diseases and the underlying molecular mechanisms remain unclear.This study aims to evaluate the metabolite profile, pharmacokinetics, toxicity, molecular targets, and potential biological activities of AST. Thirty-one AST metabolites formed through Phase II reactions (O-glucuronidation, O-sulfation, and methylation) were found.AST and its metabolites partially violate Lipinski’s Rule of Five, including molecular weight and hydrogen bond donors, impacting drug-likeness. However, AST and its metabolites have favourable safety and potential anti-neurodegenerative and antidepressant effects.AST shows strong binding affinities with key neuroinflammatory targets, including IL1B, IL6, TNF, NOS2, PTGS2, SERT, caspase-3, caspase-8, and GABAa receptor, and network analysis highlights its association with neuroinflammatory pathways.Collectively, these findings support AST as a potential neurotherapeutic candidate and offer a basis for further <i>in vitro</i> and <i>in vivo</i> validation. Astragalin (AST), a flavonoid, shows promise for neurodegenerative diseases like Parkinson’s disease (PD), cognitive impairment (CI), and depression. However, its efficacy in treating neurodegenerative diseases and the underlying molecular mechanisms remain unclear. This study aims to evaluate the metabolite profile, pharmacokinetics, toxicity, molecular targets, and potential biological activities of AST. Thirty-one AST metabolites formed through Phase II reactions (O-glucuronidation, O-sulfation, and methylation) were found. AST and its metabolites partially violate Lipinski’s Rule of Five, including molecular weight and hydrogen bond donors, impacting drug-likeness. However, AST and its metabolites have favourable safety and potential anti-neurodegenerative and antidepressant effects. AST shows strong binding affinities with key neuroinflammatory targets, including IL1B, IL6, TNF, NOS2, PTGS2, SERT, caspase-3, caspase-8, and GABAa receptor, and network analysis highlights its association with neuroinflammatory pathways. Collectively, these findings support AST as a potential neurotherapeutic candidate and offer a basis for further <i>in vitro</i> and <i>in vivo</i> validation. 31 metabolite products from astragalin (AST) were foundCore Phase II reactions: O-sulphation, O-glucuronidation, and methylationAST showed high binding affinity with GABAa and SERTBiological activities: antioxidant, anti-inflammatory, and anti-apoptoticMolecular mechanisms: miR-143-3p, 203a-3p, 26a-5p,146-5p, NFKB2, NFKB1, and NFE2L2 31 metabolite products from astragalin (AST) were found Core Phase II reactions: O-sulphation, O-glucuronidation, and methylation AST showed high binding affinity with GABAa and SERT Biological activities: antioxidant, anti-inflammatory, and anti-apoptotic Molecular mechanisms: miR-143-3p, 203a-3p, 26a-5p,146-5p, NFKB2, NFKB1, and NFE2L2