Artemisiae Argyi exosome-like nanovesicles alleviate ALF by reducing oxidative stress and inhibiting inflammation through the TLR4/NLRP3/Nrf2 axis

In recent years, plant-derived exosome-like nanovesicles (PELNVs) have attracted considerable research interest as emerging therapeutic adjuvants or delivery vehicles. This study aimed to develop exosome-like nanovesicles derived from Artemisia argyi (AELNVs) and evaluate their therapeutic potential in ameliorating LPS/D-GalN-induced acute liver failure (ALF) in mice. In our in vitro study, oral administration of AELNVs significantly ameliorates liver pathological damage, reduced systemic inflammatory cytokine levels, and improved survival in mice with ALF. We demonstrated that AELNVs inhibited the TLR4/NF-κB/NLRP3 axis and suppress hepatocyte apoptosis, while concurrently activating the Nrf2-CYP2A5 pathway to alleviate oxidative stress and hepatotoxicity. Analysis of hepatic chemokines revealed that AELNVs mitigated the hepatic immune response by suppressing the CCL5/7-CCR5 and CXCL9/10/11-CXCR3 chemokine axes. Furthermore, RNA-miRNA alignment analysis identified MIR2916 as a key mediator through which AELNVs modulated the TLR4 and its downstream signaling pathways. Collectively, these findings reveal the therapeutic potential of AELNVs as a nanotherapeutic agent for ALF.