Apoptotic and Anti-Inflammatory Effects of Eupatorium japonicum Thunb. in Rheumatoid Arthritis Fibroblast-Like Synoviocytes

Abstract EN

Rheumatoid arthritis (RA) is a chronic autoimmune inflammatory disease characterized by synovitis, hyperplasia, and the destruction of bone and cartilage.

A variety of immunosuppressive biological agents have been developed because the pathogenesis of RA is related predominantly to the inflammatory response.

However, rheumatoid arthritis fibroblast-like synovial cells (RAFLS), which are known to play an important role in RA progression, exhibit resistance to immunosuppressants through cancer-like properties.

In this study, we identified a novel therapeutic compound for RA, which reduced inflammation and the abnormal proliferation of RAFLS in natural product library made from Korean native plants.

Eupatorium japonicum Thunb.

(EJT) extract, a component of the natural product library, most effectively reduced viability through the induction of ROS-mediated apoptosis in a dose-dependent manner.

In addition, the increased ROS induced the expression of ATF4 and CHOP, key players in ER stress-mediated apoptosis.

Interestingly, EJT extract treatment dose-dependently reduced the expression of IL-1β and the transcription of MMP-9, which were induced by TNF-α treatment, through the inhibition of NF-κB and p38 activation.

Collectively, we found that EJT extract exerted apoptotic effects through increases in ROS production and CHOP expression and exerted anti-inflammatory effects through the suppression of NF-κB activation, IL-1β expression, and MMP-9 transcription.