Broccoli-Derived Exosome-like Nanoparticles Alleviates Metabolic Dysfunction-Associated Steatotic Liver Disease Through Modulating the Gut-Liver Axis.

Abstract

: Metabolic dysfunction-associated steatohepatitis (MASLD) represents a prevalent liver disease worldwide. It is crucial to maintain the stability of the gut-liver axis in order to inhibit the advancement of MASLD. Broccoli-derived exosome-like nanoparticles (BDENs) can alleviate constipation and improve colitis. This study investigated whether BDENs possess therapeutic potential for improving induced MASLD by the gut-liver axis.: BDENs were fractionated from fresh broccoli using differential centrifugation, and the microRNAs were identified and analyzed. 24 male C57BL/6J mice (6 weeks old) were randomized into the control group, HFD group, and BDENs group, with 8 mice per group. After 8 weeks of high-fat diet modeling, the BDENs group accepted BDENs daily oral gavage of 100 mg/kg (B.W.), while the control and HFD groups accepted 1 &#xd7; PBS. Four weeks after BDENs intervention, analysis was conducted on liver injury markers, liver tissue pathology, intestinal barrier, cecal content metabolomics and fecal 16S rRNA, serum inflammatory factors, and hepatic inflammation.: BDENs identified 1659 miRNAs associated with physiological processes such as immunity, antioxidant defense, and fatty acid biosynthesis. BDENs significantly reduced weight and ALT/AST ratio (< 0.05). Furthermore, BDENs attenuated hepatic histopathological damage and lipid accumulation. For the gut-liver axis, BDENs maintained intestinal barrier, regulated intestinal bile acid metabolism and restored the gut microbiota. Additionally, BDENs reduced serum LPS level (< 0.01) and suppressed hepatic inflammation, including F4/80 and IL-6, IL-1&#x3b2; (< 0.0001).: Oral BDENs therapy demonstrates potential for ameliorating MASLD.