Nitric oxide and α-glucosidase inhibitors from Ludwigia adscendens: An integrated in vitro and in silico study

Ludwigia adscendens (Onagraceae) has been traditionally used for the treatment of inflammatory and metabolic disorders; however, the bioactive constituents responsible for these effects remain insufficiently characterized. In this study, twelve secondary metabolites (1-12), including triterpenoids, flavonoids, and phenolic acids, were isolated from L. adscendens and evaluated for their inhibitory effects on nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated RAW264.7 macrophages and α-glucosidase activity in vitro. Among the tested compounds, sulfuretin (8) exhibited the most potent NO inhibitory activity (IC₅₀ = 12.3 ± 0.56 μM), while uvaol (3) and ursolic aldehyde (4) showed strong α-glucosidase inhibition (IC₅₀ = 5.6 ± 0.7 and 4.2 ± 0.3 μM, respectively), surpassing acarbose. Molecular docking studies against inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin-8 (IL-8), and oligo-1,6-glucosidase supported the experimental findings, revealing favorable binding affinities and key interactions consistent with the observed structure-activity relationships. In silico ADMET (absorption, distribution, metabolism, excretion, and toxicity) analysis predicted acceptable drug-likeness and low acute toxicity for the active compounds. Collectively, these results identify sulfuretin as a promising dual anti-inflammatory and antidiabetic scaffold, while triterpenoid derivatives emerge as potent and selective α-glucosidase inhibitors, providing a rational basis for further medicinal chemistry optimization.