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

Int Immunopharmacol. 2025 Aug 28:161:115046. doi: 10.1016/j.intimp.2025.115046. Epub 2025 Jun 14.

Abstract

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.

Keywords: Ginseng; Inflammation; Plant-derived vesicle-like nanoparticles; Rheumatoid arthritis; Small RNAs.

MeSH terms

  • Animals
  • Arthritis, Experimental* / drug therapy
  • Arthritis, Rheumatoid* / drug therapy
  • Exosomes* / genetics
  • Exosomes* / metabolism
  • Humans
  • MAP Kinase Signaling System / drug effects
  • Macrophages / drug effects
  • Male
  • Mice
  • Mice, Inbred DBA
  • MicroRNAs* / genetics
  • Nanoparticles
  • Panax* / genetics
  • Proto-Oncogene Proteins p21(ras)* / genetics
  • Proto-Oncogene Proteins p21(ras)* / metabolism

Substances

  • MicroRNAs
  • Proto-Oncogene Proteins p21(ras)
  • Hras protein, mouse