Encapsulation of rutin in Lactobacillus rhamnosus-derived extracellular vesicles enhances its alleviative effects against alcohol-induced liver injury

Abstract

Rutin is a dietary flavonoid that performs various physiological activities. However, its application is limited by low water-solubility, chemical stability, and bioaccessibility. In this study, rutin was encapsulated in Lactobacillus-derived extracellular vesicles (Ru-LAEVs) to improve the functionality. Initially, LAEVs were isolated, purified, and characterized. Then, Ru-LAEVs were prepared using a simple, affordable, and environmentally friendly pH-driven method. The effect of LAEVs on the solubility, stability, bioaccessibility, and therapeutic effects against alcoholic liver injury of rutin were then evaluated. Our results showed that rutin was successfully encapsulated by LAEVs. The encapsulation rate of Ru-LAEVs has reached 90%. Compared with free rutin, the UV and thermal stability of Ru-LAEVs improved by 23.6% and 12.8%, respectively, and the bioavailability was increased by 19%. Ru-LAEVs tend to accumulate in the livers of mice without cytotoxic. Compared with the alcohol-treated group, mice in the Ru-LAEVs-treated group had lower liver index, liver damage and inflammation levels. Specifically, reduced serum levels of AST, ALT, ALP, and TG were observed. The hepatic levels of F4/80, TNF-α, IL-6, IL-1β, and MDA were reduced, while hepatic levels of IL-10, SOD, and GSH were increased. And its alleviative effects against alcoholic liver injury were significantly improved by encapsulation. This may be due to the ability of the Ru-LAEVs to regulate the intestinal flora of alcohol-fed mice and the relative protein levels of Nrf-2, HO-1, and CYP2E1 in the liver. The results of this study may be used to create probiotic-derived EVs for the encapsulation, protection, and delivery of biologically active substances, which could be applied in novel functional foods and beverages.