AUTHOR=Guohui Nan , Tingna Xie , Qinghui He , Hongchun Yu , Jing Peng , Shiyin Jiang , Li Li , Huawei Yuan , Daijing Wei , Qi Wu TITLE=Transcriptomic and metabonomic profiling unveils the mechanism of Tartary buckwheat and kiwi co-fermentation products in hyperlipidemia treatment JOURNAL=Frontiers in Pharmacology VOLUME=Volume 16 - 2025 YEAR=2025 URL=https://www.frontiersin.org/journals/pharmacology/articles/10.3389/fphar.2025.1572593 DOI=10.3389/fphar.2025.1572593 ISSN=1663-9812 ABSTRACT=IntroductionTartary buckwheat (Fagopyrum tataricum, TB), a flavonoid-rich plant limited by anti-nutritional metabolites.MethodsTB was co-fermented with kiwi juice (TB-KW) through alcohol fermentation to improve flavonoid extraction and utilization. The flavonoid profile of TB-KW was analyzed through untargeted metabolomics. The anti-hyperlipidemic effects of TB-KW were assessed in zebrafish maintained on a high-fat diet through transcriptomics and metabolomics.ResultsUntargeted metabolomic analysis showed that flavonoids originating from TB, including quercetin, luteolin, quercitrin, rutin, and kaempferide, were significantly enriched in TB-KW. The data further showed that TB-KW significantly reduced lipid accumulation in zebrafish. Metabolomic profiling revealed 24 core differential metabolites (DEMs), spanning glycerophospholipids, sphingolipids, glycerolipids, and fatty acyls. Transcriptome analysis showed that TB-KW significantly regulated genes such as PLTP, ApoC1, SOAT2, SCARB1, PLA2G12B, and HMGCRa.DiscussionThese genes are associated with cholesterol metabolism and pathways linked to fat digestion and absorption, and they show a particular capacity to increase HDL synthesis. This study suggests the potential of TB-KW in improving flavonoid bioavailability and in the prevention and treatment of hyperlipidemia.