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

ABSTRACT

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.