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[A. Biochemistry/Molecular Biology] A-21
Therapeutic Effects of Fermeted Lettuce Extract in Mice with
Collagen-Induced Arthritis and Human Fibroblast-like
Synoviocytes
Jisu Park ¹, Ji Won Kim¹, Jaehoon Jung¹, Ji Hyeon Ryu¹, Yong-Il Shin¹,²*
¹Research Institute for Convergence of Biomedical Science and Technology, Pusan National University Yangsan
Hospital, Yangsan 50612, Korea, ²Department of Rehabilitation Medicine, Pusan National University School of
Medicine, Yangsan 50612, Korea
Lettuce (Lactuca sativa L.) has a variety of biological activities with strong anti-oxidant and anti-inflammatory
potentials. However, little is known regarding the anti-arthritic effects of lettuce. Here, we performed to identify the
therapeutic effects and the underlying mechanisms of fermented lettuce extract (FLE) on collagen-induced arthritis
(CIA) in mice and fibroblast-like synoviocytes derived from rheumatoid arthritis (RA) patients. DBA/1 mice were
immunized with bovine type II collagen and were orally administrated FLE for 14 consecutive days. FLE significantly
reduced the severity of arthritis, synovial inflammation, bone erosion, and destruction in CIA mice. FLE highly
inhibited the production of pro-inflammatory cytokines in joint tissues. The inhibitory effect of FLE on the anti-
arthritic effects in CIA mice was similar to that of methotrexate (MTX), typically used to treat RA. In vitro, FLE dose-
and time-dependently inhibits the proliferation in MH7A cells. Moreover, FLE increased GFP-LC3 puncta formation
and both LC3-II and p62 expression in MH7A cells. This result suggested that FLE could induce the formation of
autophagosome in the early of autophagy, but inhibit the degradation of autophagosome in a later stage of
autophagy. These results showed that FLE could be used as a potential therapeutic agent for the treatment of RA.

