Analysis of the therapeutic potential of astragalin: insights into target interactions and mechanisms

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 in vitro and in vivo 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 in vitro and in vivo validation.

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

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