Dendrobium officinale-derived extracellular nanovesicles alleviate metabolic disorders and intestinal barrier dysfunction in db/db mice

Natural products rich in plant polyphenols, polysaccharides, and flavonoids, particularly those derived from traditional Chinese medicinal herbs, gained significant attention as functional foods. This study investigated extracellular nanovesicles derived from Dendrobium officinale Kimura & Migo stem (DOS-ELNs) for the treatment of metabolic dysfunction-associated steatotic liver disease (MASLD). DOS-ELNs displayed typical vesicular morphology with an average diameter of 181.9 ± 51.8 nm and contained abundant bioactive components, including proteins, RNA, lipids, polysaccharides, and flavonoids. DOS-ELNs demonstrated remarkable stability, maintaining structural integrity under enzymatic and acidic conditions that mimic gastrointestinal environments. In vitro, DOS-ELNs enhanced cellular energy metabolism in AML-12 hepatocytes treated with PA by activating the AMPK signaling pathway, reducing lipogenic factors, and alleviating LPS-induced inflammation. Additionally, DOS ELNs alleviate LPS induced barrier damage in Caco-2 cells by enhancing the expression of tight junction proteins. In vivo, they effectively modulated hepatic lipid metabolism, restored intestinal barrier integrity, and reshaped gut microbiota composition. Overall, these findings suggest that DOS-ELNs represent a promising natural nanotherapeutic for MASLD and highlight Dendrobium officinale as a valuable source for the development of functional foods targeting metabolic disorders.