Cyanidin-3-rutinoside from Mori Fructus ameliorates dyslipidemia via modulating gut microbiota and lipid metabolism pathway

Dyslipidemia is responsible for pathologies of cardiovascular diseases and gut microbiota plays an essential role in lipid metabolism. Dietary supplementation is an important supplement to medicine in management of dyslipidemia. Mori Fructus is a popular Asia medical food with various pharmacological benefits including anti-hyperlipidemia. Cyanidin-3-rutinoside (C3R) is the main anthocyanin component in Mori Fructus, but the lipid-lowering effect and underlying mechanism of Mori Fructus-derived C3R remains unknown. In this study, we assessed the beneficial effect of Mori Fructus-derived C3R in HFD-induced hyperlipidemic mice and investigated its potential mechanism through 16S rRNA-based metagenomics and transcriptomics analysis. Our results showed that C3R from Mori Fructus significantly decreased serum lipid levels and attenuated hepatic damage induced by HFD. Analysis of the gut microbiota revealed that C3R altered the specific gut micorbiota but not changed its diversity. Among changed genera, Family_XIII_UCG-001 was significantly enriched by C3R, and it was positively associated with HDL-c, but negatively related with TC, TG, LDL-c, insulin and body weight. Transcriptomic analysis showed that C3R activates the lipid metabolism related pathways including MAPK signaling pathway, Rap1 signaling pathway, Ras signaling pathway and PI3K-Akt signaling pathway. Additionally, correlation analysis unraveled that C3R-enriched Family_XIII_UCG-001 was negatively associated with C3R-inhibited genes of Camk2a, Eef1a2, Gad1, Kif5a and Sv2b, which further positively related with TC, TG, LDL-c, insulin and body weight, but negatively associated with HDL-c. In sum, C3R may inhibit expression of immune-related genes by enriching the Family_XIII_UCG-001 genus, further ameliorating lipid metabolism disorders in HFD-challenged mice. This study provides an optional strategy for the daily management of dyslipidemia.