Seomae mugwort and jaceosidin attenuate osteoarthritic cartilage damage by blocking IκB degradation in mice

J Cell Mol Med. 2020 Jul;24(14):8126-8137. doi: 10.1111/jcmm.15471. Epub 2020 Jun 11.

Abstract

Seomae mugwort, a Korean native variety of Artemisia argyi, exhibits physiological effects against various diseases. However, its effects on osteoarthritis (OA) are unclear. In this study, a Seomae mugwort extract prevented cartilage destruction in an OA mouse model. In vitro and ex vivo analyses revealed that the extract suppressed MMP3, MMP13, ADAMTS4 and ADAMTS5 expression induced by IL-1β, IL-6 and TNF-α and inhibited the loss of extracellular sulphated proteoglycans. In vivo analysis revealed that oral administration of the extract suppressed DMM-induced cartilage destruction. We identified jaceosidin in Seomae mugwort and showed that this compound decreased MMP3, MMP13, ADAMTS4 and ADAMTS5 expression levels, similar to the action of the Seomae mugwort extract in cultured chondrocytes. Interestingly, jaceosidin and eupatilin combined had similar effects to Seomae mugwort in the DMM-induced OA model. Induction of IκB degradation by IL-1β was blocked by the extract and jaceosidin, whereas JNK phosphorylation was only suppressed by the extract. These results suggest that the Seomae mugwort extract and jaceosidin can attenuate cartilage destruction by suppressing MMPs, ADAMTS4/5 and the nuclear factor-κB signalling pathway by blocking IκB degradation. Thus, the findings support the potential application of Seomae mugwort, and particularly jaceosidin, as natural therapeutics for OA.

Keywords: IκB; Seomae mugwort; cartilage destruction; jaceosidin; matrix metalloproteinase; nuclear factor-kappa B; osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Artemisia / chemistry*
  • Arthritis, Experimental
  • Biomarkers
  • Cartilage, Articular / drug effects*
  • Cartilage, Articular / metabolism*
  • Cartilage, Articular / pathology
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chondrocytes / drug effects
  • Chondrocytes / metabolism
  • Disease Models, Animal
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Gene Expression
  • I-kappa B Proteins / metabolism*
  • Immunohistochemistry
  • Interleukin-1beta / pharmacology
  • Matrix Metalloproteinases / metabolism
  • Mice
  • Models, Biological
  • NF-kappa B / metabolism
  • Osteoarthritis / drug therapy
  • Osteoarthritis / etiology
  • Osteoarthritis / metabolism*
  • Osteoarthritis / pathology
  • Plant Extracts / chemistry
  • Plant Extracts / pharmacology*
  • Proteoglycans / metabolism
  • Proteolysis
  • Signal Transduction / drug effects

Substances

  • Biomarkers
  • Flavonoids
  • I-kappa B Proteins
  • Interleukin-1beta
  • NF-kappa B
  • Plant Extracts
  • Proteoglycans
  • jaceosidin
  • Matrix Metalloproteinases