Ginseng exosomal miRNA ameliorates rheumatoid arthritis by mediating KRAS-MAPK signaling.

As crucial roles of interkingdom crosstalk between plants and mammalian, plant-derived vesicle- like nanoparticles (PDVLNs) have various bioactivity and higher penetrability, showing potentiality to develop as therapeutic agents and drug carriers. Here, we isolated nanoparticles from Ginseng, a crucial candidate herbal medicine for rheumatoid arthritis (RA), and found that Ginseng-derived nanoparticles (GDNPs) could spread into joints and exhibited anti-inflammatory effect in collagen-induced arthritis (CIA) mice. Mechanistically, GDNPs delivered ginseng specific pgi-miR6135j into synovial macrophages to directly inhibit KRAS expression, a positive regulator of MAPK pathway, resulting reduced phosphorylation levels of MAPK pathway. Our study reveals the therapeutic mechanism of Ginseng in RA and suggest potential biotherapeutic applications of PDVLNs.