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Co-production of high-purity floridoside and isofloridoside ameliorates MASH via Parabacteroides goldsteinii-UDCA-FXR enterohepatic axis

作者:Shuang Li, Rong Guo, Linxiao Sun, Peng Zhu, Tingting Wang, JianJun Zheng, H Z Chen, Hui Li · 发表于:Chinese Medicine · 年份:2026 · DOI:10.1186/s13020-026-01450-9 · 研究领域:Seaweed-derived Bioactive Compounds、Gut microbiota and health、Fibroblast Growth Factor Research

BACKGROUND: Metabolic dysfunction-associated steatohepatitis (MASH), the progressive form of metabolic dysfunction-associated fatty liver disease (MAFLD), is tightly linked to gut microbiota dysbiosis and disrupted bile acid (BA) homeostasis. Floridoside (Flor), a marine glycoside from the edible seaweed Pyropia haitanensis (P. haitanensis), exerts promising biological activities. However, protocols for its high-purity preparation and the mechanisms underlying its anti-MASH effects remain unclear. PURPOSE: To develop a protocol for the preparation of high-purity Flor and its isomer isofloridoside (Isoflor) from P. haitanensis, and to elucidate how Flor alleviates MASH via regulating gut microbiota and BA metabolism. METHODS: High-purity Flor and Isoflor were isolated via integrated chromatography, with their chemical structures confirmed by LC-MS and NMR. Anti-MASH efficacy was evaluated in a high-fat diet (HFD)-induced murine MASH model. The underlying mechanisms were explored using multi-omics analyses, including transcriptomics, gut microbiota metagenomics and BA-targeted metabolomics, and further validated by molecular docking, molecular dynamics simulation and western blotting; the compounds' biosafety was evaluated using zebrafish. RESULTS: High-purity Flor and Isoflor were successfully isolated, each with a purity of ≥ 99.0%. Both compounds exhibited a favorable biosafety profile and comparable lipid-lowering activity in zebrafish. In HFD-induced murine MASH models, Fl...