Work

Flavonoid–Sesquiterpenoid Hybrids from the Leaves of Syzygium simile and Their Anti-Lipid Droplet Accumulation Activities

Year: 2025

Type: article

Abstract: High Resolution Image Download MS PowerPoint Slide Metabolic-associated fatty liver disease (MAFLD) represents a spectrum of hepatic disorders characterized by excessive lipid accumulation in the liver with a global prevalence rate of 30%. Despite their increasing prevalence, current therapeutic interventions remain suboptimal, constrained by substantial adverse effects and prohibitive treatment costs. Through an anti-lipid droplet (LD) accumulation screening platform, over 3000 methanolic extracts of Formosan plants were evaluated. Among them, the leaf extract of Syzygium simile demonstrated significant inhibitory activity of 40% at 25 μg/mL, emerging as the most promising species. Through bioassay-guided fractionation, 20 compounds were isolated from the n -hexane layer of the leaves, including nine new compounds [simisyzygins C–G ( 1 – 5, respectively) and simicadinenes A–D ( 6 – 9, respectively)] and 11 known compounds. These new compounds possess unique carbon skeletons characterized as flavonoid–sesquiterpenoid hybrids. Their structures were elucidated by the analysis of spectroscopic data. The structures of 1, 4, 5, and 11 were further confirmed by single-crystal X-ray diffraction analysis. Syzygioblane B ( 11 ) demonstrated the most potent inhibition of LD accumulation in Huh7 cells, achieving a 64.1% reduction at 40 μM with dose-dependency (5–40 μM) and no observable cytotoxicity. This is the first phytochemical and biological investigation of S . simile that highlights its potential as a promising botanical drug candidate for treating LD accumulation-related diseases.

Source: Journal of Natural Products

DOI: 10.1021/acs.jnatprod.5c00157