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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

