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               Ugonin P facilitates chondrogenic properties in chondrocytes by inhibiting
               miR-3074-5p  production:  Implications  for  the  treatment  of  arthritic
               disorders
                                                                    4
                                                    #,3
                                                                                               3
               Ting-Kuo Chang,   #,1,2  Trung-Loc Ho,  Yen-You Lin,  Le Huynh Hoai Thuong,  Kuan-
                                          6,7
               Ying Lai,  Chun-Hao Tsai,  Chih-Chuang Liaw,*      ,5,8  Chih-Hsin Tang* ,3,9,10,11
                         5
               1  Department of Medicine, Mackay Medical College, New Taipei, Taiwan
               2  Division of Spine Surgery, Department of Orthopedic Surgery, MacKay Memorial Hospital,
                 New Taipei, Taiwan
               3  Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan
               4  Translational Medicine Center, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
               5  Department of Marine Biotechnology and Resources, National Sun Yat-sen University,
                 Kaohsiung, Taiwan
               6  Department of Sports Medicine, College of Health Care, China Medical University,
                 Taichung, Taiwan
               7  Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan
               8  Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung, Taiwan
               9  Department of Pharmacology, School of Medicine, China Medical University, Taichung,
                 Taiwan
               10  Chinese Medicine Research Center, China Medical University, Taichung, Taiwan
               11  Department of Medical Laboratory Science and Biotechnology, College of Medical and
                 Health Science, Asia University, Taichung, Taiwan
               #  These authors contributed equally to this work
               *E-mail: chtang@mail.cmu.edu.tw; ccliaw@mail.nsysu.edu.tw
               Abstract
                  Arthritis is a chronic inflammatory disease that causes joint damage, with osteoarthritis (OA)
               and rheumatoid arthritis (RA) being the most common types. Both conditions are characterized
               by  cartilage  degradation  due  to  an  imbalance  between  repair  and  breakdown  processes.
               Chondrocytes,  the  key  cells  in  articular  cartilage,  maintain  its  structure  by  producing  an
               extracellular matrix rich in aggrecan and type II collagen (COL2). MicroRNAs (miRNAs),
               small noncoding RNAs, regulate genes critical for cartilage balance and are involved in the
               progression and treatment of OA and RA. Recently, herbal medicines have gained attention for
               arthritis treatment. Ugonin P, a flavonoid from Helminthostachys zeylanica Hook, is known for
               its antioxidant and anticancer effects, but its role in cartilage homeostasis is unclear. This study
               explores  ugonin  P's  chondrogenic  effects  and  its  molecular  mechanisms  involving  miRNA
               regulation. Analysis of Gene Expression Omnibus (GEO) data and clinical samples revealed
               reduced aggrecan and COL2 levels in OA and RA, while miR-3074-5p levels were elevated,
               suppressing these proteins. Ugonin P, without affecting cell viability, enhanced aggrecan and
               COL2 production and promoted chondrocyte differentiation by downregulating miR-3074-5p
               and activating MAPK pathways. These findings suggest ugonin P as a promising therapeutic
               candidate for arthritis management.
               Keywords: Arthritis; Helminthostachys zeylanica; Ugonin P; miR-3074-5p; Aggrecan; Type II
     	
