Inflammatory bowel disease (IBD) is closely linked to the homeostasis of the intestinal environment, and exosomes can be used to treat IBD due to their high biocompatibility and ability to be effectively absorbed by the intestinal tract. However, Ginseng-derived nanoparticles (GDNPs) have not been studied in this context and their mechanism of action remains unclear. Here, we investigated GDNPs ability to mediate intercellular communication in a complex inflammatory microenvironment in order to treat IBD. We found that GDNPs scavenge reactive oxygen species from immune cells and intestinal epithelial cells, inhibit the expression of pro-inflammatory factors, promote the proliferation and differentiation of intestinal stem cells, as well as enhancing the diversity of the intestinal flora. GDNPs significantly stabilise the intestinal barrier thereby promoting tissue repair. Overall, we proved that GDNPs can ameliorate inflammation and oxidative stress in vivo and in vitro, acting on the TLR4/MAPK and p62/Keap1/Nrf2 pathways, and exerting an anti-inflammatory and antioxidant effect. GDNPs mitigated IBD in mice by reducing inflammatory factors and improving the intestinal environment. This study offers new evidence of the potential therapeutic effects of GDNPs in the context of IBD, providing the conceptual ground for an alternative therapeutic strategy. Graphical Abstract

Accumulation of amyloid-β (Aβ), which results in the formation of senile plaques that cause oxidative damage and neuronal cell death, has been accepted as the major pathological mechanism of Alzheimer’s disease (AD). Hence, inhibition of Aβ-induced oxidative damage and neuronal cell apoptosis represents the effective strategies in combating AD. Ginsenoside Re (Re) has pharmacological effects against Aβ-induced neurotoxicity. However, its molecular mechanism remains elusive. The present study evaluated the effect of Re against Aβ-induced cytotoxicity and apoptosis in SH-SY5Y cells, and investigated the underlying mechanism. We demonstrate that Re inhibits the Aβ-triggered mitochondrial apoptotic pathway, as indicated by maintenance of mitochondrial functional, elevated Bcl-2/Bax ratio, reduced cytochrome c release, and inactivation of caspase-3/9. Re attenuated Aβ-evoked reactive oxygen species (ROS) production, apoptosis signal-regulating kinase 1 (ASK1) phosphorylation, and JNK activation. ROS-scavenging abrogated the ability of Re to alter ASK-1 activation. Simultaneously, inhibition of JNK abolished Re-induced Bax downregulation in Aβ-challenged SH-SY5Y cells. In addition, Re enhanced activation of the nuclear factor-E2-related factor 2 (Nrf2) in Aβ-induced SH-SY5Y cells. Knockdown of Nrf2 by small interfering RNA targeting Nrf2 abolished the protective effect of Re. Our findings indicate that Re could be a potential therapeutic approach for the treatment of AD.

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. 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. 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. In summary, GEs may be a potential treatment for inflammatory bowel disease, and targeting autophagy and macrophage polarisation may help alleviate intestinal inflammation.