Abstract

Derris scandens (Roxb.) Benth. (Fabaceae) is a medicinal plant with anti-inflammatory properties. Its stem extract is approved in Thailand for treating musculoskeletal pain. However, sustainability concerns necessitate exploring alternative sources such as leaves. This study aimed to compare the phytochemical profiles and anti-inflammatory activity of D. scandens leaves and stems collected from different geographical locations. High-performance liquid chromatography with diode-array detection (HPLC–DAD) was employed to quantify isoflavones in extracts prepared using various ethanol concentrations. Anti-inflammatory activity was assessed through nitric oxide (NO) secretion inhibition in lipopolysaccharide (LPS)-induced RAW 264.7 macrophage cells. Geographical location influenced metabolite profiles and biological activity. Leaves contained isoangustone A (up to 26.6 μg/mg) and lupalbigenin (up to 0.98 μg/mg), while stems exhibited higher lupalbigenin levels (up to 296 μg/mg) and additional metabolites, including derrisisoflavone A and 6,8-diprenylgenistein. At 25 μg/mL, NO inhibition by derrisisoflavone A (34.3%) and 6,8-diprenylgenistein (23.3%) was higher than that of leaf-derived compounds such as derrubone (31.0%) and isoangustone A (18.0%). Ethanolic extracts (50 μg/mL) of the stems demonstrated greater NO inhibition (9.44%–59.6%) compared to the leaves (6.59%–39.2%). While D. scandens leaves offer an alternative phytochemical resource, their distinct chemical and biological profiles limit their substitution for the stems as a source of anti-inflammatory metabolites. The findings support the regulatory approval of the stems as an essential Thai medicine. Molecular docking revealed that lupalbigenin showed the strongest binding to COX-1, COX-2, and 5-LOX, supporting its potential as a dual COX/LOX inhibitor for anti-inflammatory drug development.