Kim Jisu, Zhang Shuya, Zhu Ying, Wang Ruirui, Wang Jianxin
Department of Pharmaceutics, School of Pharmacy, Fudan University & Key Laboratory of Smart Drug Delivery, Ministry of Education, Shanghai, China.
Department of Integrative Oncology, Fudan University Shanghai Cancer Center, Shanghai, China.
J Ginseng Res. 2023 Sep;47(5):627-637. doi: 10.1016/j.jgr.2023.01.004. Epub 2023 Jan 7.
Damage to the healthy intestinal epithelial layer and regulation of the intestinal immune system, closely interrelated, are considered pivotal parts of the curative treatment for inflammatory bowel disease (IBD). Plant-based diets and phytochemicals can support the immune microenvironment in the intestinal epithelial barrier for a balanced immune system by improving the intestinal microecological balance and may have therapeutic potential in colitis. However, there have been only a few reports on the therapeutic potential of plant-derived exosome-like nanoparticles (PENs) and the underlying mechanism in colitis. This study aimed to assess the therapeutic effect of PENs from , ginseng-derived exosome-like nanoparticles (GENs), in a mouse model of IBD, with a focus on the intestinal immune microenvironment.
To evaluate the anti-inflammatory effect of GENs on acute colitis, we treated GENs in Caco2 and lipopolysaccharide (LPS) -induced RAW 264.7 macrophages and analyzed the gene expression of pro-inflammatory cytokines and anti-inflammatory cytokines such as TNF-α, IL-6, and IL-10 by real-time PCR (RT-PCR). Furthermore, we further examined bacterial DNA from feces and determined the alteration of gut microbiota composition in DSS-induced colitis mice after administration of GENs through 16S rRNA gene sequencing analysis.
GENs with low toxicity showed a long-lasting intestinal retention effect for 48 h, which could lead to effective suppression of pro-inflammatory cytokines such as TNF-α and IL-6 production through inhibition of NF-κB in DSS-induced colitis. As a result, it showed longer colon length and suppressed thickening of the colon wall in the mice treated with GENs. Due to the amelioration of the progression of DSS-induced colitis with GENs treatment, the prolonged survival rate was observed for 17 days compared to 9 days in the PBS-treated group. In the gut microbiota analysis, the ratio of Firmicutes/Bacteroidota was decreased, which means GENs have therapeutic effectiveness against IBD. Ingesting GENs would be expected to slow colitis progression, strengthen the gut microbiota, and maintain gut homeostasis by preventing bacterial dysbiosis.
GENs have a therapeutic effect on colitis through modulation of the intestinal microbiota and immune microenvironment. GENs not only ameliorate the inflammation in the damaged intestine by downregulating pro-inflammatory cytokines but also help balance the microbiota on the intestinal barrier and thereby improve the digestive system.
健康的肠道上皮层损伤与肠道免疫系统调节密切相关，被认为是炎症性肠病（IBD）治疗的关键部分。植物性饮食和植物化学物质可通过改善肠道微生态平衡来支持肠道上皮屏障中的免疫微环境，以实现免疫系统的平衡，并且可能对结肠炎具有治疗潜力。然而，关于植物来源的外泌体样纳米颗粒（PENs）在结肠炎中的治疗潜力及其潜在机制的报道较少。本研究旨在评估人参来源的外泌体样纳米颗粒（GENs）对IBD小鼠模型的治疗效果，重点关注肠道免疫微环境。
为了评估GENs对急性结肠炎的抗炎作用，我们在Caco2细胞和脂多糖（LPS）诱导的RAW 264.7巨噬细胞中处理GENs，并通过实时聚合酶链反应（RT-PCR）分析促炎细胞因子和抗炎细胞因子如肿瘤坏死因子-α（TNF-α）、白细胞介素-6（IL-6）和白细胞介素-10（IL-10）的基因表达。此外，我们进一步检测了粪便中的细菌DNA，并通过16S核糖体RNA（rRNA）基因测序分析确定了给予GENs后葡聚糖硫酸钠（DSS）诱导的结肠炎小鼠肠道微生物群组成的变化。
低毒性的GENs显示出长达48小时的持久肠道滞留效应，这可通过抑制DSS诱导的结肠炎中的核因子-κB（NF-κB）来有效抑制促炎细胞因子如TNF-α和IL-6的产生。结果，在用GENs处理的小鼠中，其结肠长度更长，结肠壁增厚受到抑制。由于GENs治疗改善了DSS诱导的结肠炎的进展，与磷酸盐缓冲盐水（PBS）处理组的9天相比，观察到延长的生存率达17天。在肠道微生物群分析中，厚壁菌门与拟杆菌门的比例降低，这意味着GENs对IBD具有治疗效果。摄入GENs有望减缓结肠炎进展，增强肠道微生物群，并通过防止细菌生态失调来维持肠道稳态。
GENs通过调节肠道微生物群和免疫微环境对结肠炎具有治疗作用。GENs不仅通过下调促炎细胞因子来改善受损肠道的炎症，还有助于平衡肠道屏障上的微生物群，从而改善消化系统。
