RESUMEN
Bioinspired (or biologically inspired) drug delivery systems (DDSs) have been intensively studied in the last decades. As bioinspired DDSs, membrane vesicles, including extracellular vesicles (EVs) released from eukaryotic cells, outer membrane vesicles (OMVs) from bacteria, cell-bound membrane vesicles (CBMVs) isolated in situ from cell surfaces, membrane vesicles reorganized after the isolation of the plasma membrane of cells, and others have been rapidly developed and are attracting more and more attention. Most recently, a collection of 25 papers on the advances in membrane vesicle-based drug delivery systems was published in a Special Issue of Pharmaceutics entitled "Advances of membrane vesicles in drug delivery systems". These papers cover many related topics including the source, preparation, modification, drug loading, and in vivo administration and biodistribution of membrane vesicles (mainly extracellular vesicles or exosomes and bacterial outer membrane vesicles), as well as application of membrane vesicles as DDSs in the treatment of various diseases.
RESUMEN
Macrophages polarized to different phenotypes critically contribute to colitis development by coordinating inflammatory and anti-inflammatory processes. Herein, targeting the balance between the pro-inflammatory M1 and the anti-inflammatory M2 macrophage phenotypes can be a novel therapeutic approach for colitis. In the present study, we firstly demonstrated that tiliroside possessed the ability to alleviate the clinical symptoms of colitis as evidenced by decreased disease activity index (DAI) scores, longer colon length, reduced myeloperoxidase (MPO) activity, and improvement of colonic pathological damage in vivo. Furthermore, we showed that tiliroside modulated the balance between M1 and M2 macrophages toward a more anti-inflammatory status in colonic lamina propria but has little effect on the T cell population and epithelial barrier function in colitis mice. The macrophage depletion study further showed the protective effect of tiliroside was macrophage dependent in vivo. Mechanistically, our study demonstrated that tiliroside regulated cellular metabolism by inhibiting aerobic glycolysis in LPS and IFNγ stimulated macrophages. At the molecular level, tiliroside facilitated the proteasomal degradation of HIF-1α and downregulated mRNA expressions of HIF-1α dependent glycolytic enzymes in macrophages. Collectively, our data highlight the aberrant M1/M2 macrophage polarization in the initiation and development of ulcerative colitis and put forth the stage for considering tiliroside as a metabolic regulator in reprogramming macrophage polarization, which may serve as a promising therapeutic approach for treatment of inflammation-associated and metabolic disorders.