Anti-inflammatory flavan alkaloids from the bulbs of Hymenocallis littoralis (Jacq.) Salisb.

Hymenocallis littoralis (Jacq.) Salisb. (Coastal Spider Lily) is a rich source of structurally diverse specialized metabolites. In the present study, a phytochemical investigation of the bulbs of H. littoralis (collected in Guangdong, China) led to the isolation of 12 previously undescribed flavan alkaloids (1a/1b, 2a/2b, 3a, 4b, 5a/5b, 6a/6b, 7, and 8). These alkaloids are derived from flavan-pyrrolidinone scaffolds involving multiple stereoisomers. Additionally, two previously undescribed chromones (12, 13), one previously undescribed flavonoid (9), and twelve known flavonoids were obtained (10, 11, 14-21). The structures of the isolates were established through extensive spectroscopic analyses, including HR-ESI-MS, 1D/2D NMR, and ECD calculations. All compounds were evaluated for their anti-inflammatory effects against LPS-induced NO production in RAW 264.7 macrophages. Notably, compounds 2a, 6a, and 7 exhibited significant inhibitory activities, with IC50 values of 9.95 ± 3.05, 12.36 ± 2.68, and 23.04 ± 5.19 μM, respectively. Mechanistic studies indicated that these active compounds suppressed NF-κB activation and downregulated downstream inflammatory mediators. These findings identify H. littoralis as a promising source of unique flavan alkaloids and offer a foundation for future structure-activity relationship studies.