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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.
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