Salicifoliosides A and B: A Pair of Furan Glycoside Isomers From Chimonanthus salicifolius and Their Modulation of the Functions of Caco-2 Cells.

Chimonanthus salicifolius has traditionally been used for the treatment of gastrointestinal disorders. In this study, a systematic phytochemical investigation of this plant was conducted, leading to the isolation and identification of two previously undescribed furan glycosides, salicifoliosides A (1) and B (2). Structurally, these compounds feature a rare structural motif consisting of an α,β-unsaturated furanone aglycone esterified with a p-coumaroyl unit, a combination scarcely reported in natural products. Spectroscopic and chemical analyses established that 1 and 2 are cis-trans geometric isomers, offering a unique framework to investigate configuration-dependent properties and expanding the structural diversity of furan glycosides. To evaluate their potential relevance to functional dyspepsia (FD), we adopted a prediction‑to‑validation strategy. Network pharmacology analysis and molecular docking identified matrix metalloproteinase-2 (MMP2) as a potential target. In a lipopolysaccharide (LPS)-stimulated Caco‑2 cell model, compounds 1 and 2 significantly inhibited the secretion of MMP2 and tumor necrosis factor-α (TNF-α), consistent with the earlier in silico predictions. Notably, compound 1 also reduced interleukin-2 (IL-2) levels, suggesting a configuration-dependent effect. This study highlights a previously unrecognized natural product scaffold and provides initial evidence linking its structure to anti-inflammatory activity, offering new insights into structure-activity relationship studies and drug discovery.