Limonoid Constituents of Xylocarpus granatum Fruits from Vietnam: Antioxidant, Anti-Inflammatory Activities, and Molecular Docking Studies

Xylocarpus granatum J. Koenig, belonging to the Meliaceae family, is known for its various phytochemical constituents and significant biological activities. This study aimed to determine the limonoid components of X. granatum fruits and investigate their in vitro and in silico bioactivities. These limonoids were isolated by using chromatographic methods. Their structures were determined based on NMR and ESI-MS spectra and compared to the published data. Moreover, these compounds were assayed for in vitro antioxidant and anti-inflammatory activities. Molecular docking study was applied to understand better how these four compounds influence their anti-inflammatory capabilities. Phytochemical investigation of X. granatum fruits led to the isolation of four limonoids, including hainangranatumin A (1), xylogranatin C (2), xylocarpin F (3), and xyloccensin K (4). In addition, their antioxidant and anti-inflammatory activities were assayed and evaluated for the first time. All isolates expressed no remarkable antioxidant activity determined by the DPPH and ABTS tests. Meanwhile, the anti-inflammatory assay demonstrated that four limonoids showed significant inhibitory activity in LPS-induced RAW 264.7 macrophages with IC50 values ranging from 7.36 ± 0.23 to 12.71 ± 0.71 µg/mL (dexamethasone as the positive control, IC50 = 5.41 ± 0.46 µg/mL). In silico study shows that four limonoids (1-4) exhibited binding affinities ranging from -8.540 to -8.178 kcal/mol for TNF-α and from -9.924 to -7.014 kcal/mol for COX-2, compared to the reference compounds. The present work demonstrates that limonoids isolated from X. granatum are potential candidates for drug research aimed at treating inflammatory diseases.