Ginseng exosomes modulate M1/M2 polarisation by activating autophagy and target IKK/IкB/NF-кB to alleviate inflammatory bowel disease

BACKGROUND: Exosomes are involved in intercellular communication and regulation of the inflammatory microenvironment. In a previous study, we demonstrated that fresh ginseng exosomes (GEs) alleviated inflammatory bowel disease. However, the precise mechanism by which GEs activate the immune system and subsequently inhibit the formation of intestinal inflammatory microenvironment remains unknown. METHODS: Herein, we investigated the effects of GEs on autophagy, macrophage polarisation, intestinal inflammation, and the epithelial barrier by means of transcriptome sequencing, network pharmacology, transmission electron microscopy, immunoblotting, flow cytometry and small molecule inhibitors. RESULTS: GEs significantly activated autophagy and M2-like macrophage polarisation, which could be blocked by the autophagy inhibitor 3-methyladenine. In the co-culture system of macrophages and intestinal epithelial cells, macrophages treated with GEs secreted more interleukin-10 (IL-10) and significantly reduced Nitric oxide (NO) levels in intestinal epithelial cells in vitro. Furthermore, GEs acted directly on intestinal epithelial cells through the IKK/IкB/NF-кB signalling pathway to reduce inflammation and restore the intestinal barrier. Orally administered GEs could restore disrupted colonic barriers, alleviate inflammatory bowel responses, and regulate the polarisation of intestinal macrophages in vivo. CONCLUSION: In summary, GEs may be a potential treatment for inflammatory bowel disease, and targeting autophagy and macrophage polarisation may help alleviate intestinal inflammation.