Amelioration of colitis progression by ginseng-derived exosome-like nanoparticles through suppression of infl ammatory cytokines

다국어 초록 (Multilingual Abstract)

Background: Damage to the healthy intestinal epithelial layer and regulation of the intestinal immunesystem, closely interrelated, are considered pivotal parts of the curative treatment for inflammatorybowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironmentin the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecologicalbalance and may have therapeutic potential in colitis. However, there have been only a fewreports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlyingmechanism in colitis. This study aimed to assess the therapeutic effect of PENs from Panaxginseng, ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus onthe intestinal immune microenvironment.
Method: To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 andlipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of proinflammatorycytokines and anti-inflammatory cytokines such as TNF-a, IL-6, and IL-10 by real-timePCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alterationof gut microbiota composition in DSS-induced colitis mice after administration of GENs through16S rRNA gene sequencing analysis.
Result: GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which couldlead to effective suppression of pro-inflammatory cytokines such as TNF-a and IL-6 production throughinhibition of NF-kB in DSS-induced colitis. As a result, it showed longer colon length and suppressedthickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression ofDSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days comparedto 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidotawas decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would beexpected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis bypreventing bacterial dysbiosis.
Conclusion: GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota andimmune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine bydownregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinalbarrier and thereby improve the digestive system.