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PP-52


               Investigation of 3,4-dimethoxycinnamic acid as a novel therapeutic agent for

               rheumatoid arthritis


                                                  ,1
                                  1
               Wan-Ling Chang,  Shan-Chi Liu*

               1  Institute of Biomedical Sciences, Mackay Medical University, New Taipei City 252005,
                 Taiwan
               * E-mail: shanchiliu@mmu.edu.tw

               Abstract
                  Rheumatoid arthritis (RA) is a chronic autoimmune disease whose pathogenesis is not fully
               understood but is known to involve inflammatory cell infiltration into joints, leading to swelling,
               synovial  hyperplasia,  cartilage  damage,  and  bone  erosion.  Synovial  fibroblasts  and
               chondrocytes within the joint capsule secrete numerous pro-inflammatory factors, disrupting
               the  microenvironment  that  maintains  bone  homeostasis,  including  interleukin-1β  (IL-1β),
               interleukin-8 (IL-8), and interleukin-6 (IL-6). Current RA treatments primarily aim to alleviate
               pain with nonsteroidal anti-inflammatory drugs (NSAIDs) and steroids and to suppress disease
               progression early on with disease-modifying antirheumatic drugs (DMARDs). However, to date,
               a definitive cure for RA remains elusive, and these medications still carry side effects. Therefore,
               the quest for new, safer alternative therapies to complement RA treatment is an area of interest.
               We  aim  to  explore  the  potential  of  five  compounds  extracted  from  water  bamboo  shoots
               (Zizania latifolia; WBS)—Naringenin, Sinensetin, Ferulic Acid methyl ester, Nobiletin, and
               3,4-Dimethoxycinnamic acid—in the treatment of rheumatoid arthritis. While these compounds
               have been shown in previous studies to possess anti-inflammatory and antioxidant activities,
               their efficacy in treating rheumatoid arthritis remains unknown. Thus, we investigate their anti-
               inflammatory effects  on synovial  fibroblasts  and elucidate their inhibition  of inflammatory
               signaling pathways, hoping to offer new therapeutic avenues for RA treatment. Our preliminary
               data reveal significant expression of IL-1β and IL-8 in the synovial tissues of RA patients,
               contributing  to  synovial  inflammation  and  arthritis  formation.  Treatment  with  3,4-
               Dimethoxycinnamic acid inhibits the pro-inflammatory cytokines IL-1β and IL-8 expression
               levels  in  MH7A. Additionally,  treatment  with  3,4-Dimethoxycinnamic  acid  suppresses  the
               inflammatory pathway (MAPK pathway), leading to reduced expression of IL-1β and IL-8. Our
               data support clinical investigations using 3,4-Dimethoxycinnamic acid in RA disease

               Keywords: Rheumatoid arthritis; 3,4-Dimethoxycinnamic acid; Interleukin-1β (IL-1β);
                          Interleukin-8 (IL-8)
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