2. Academic Validation
  3. Betulin inhibits inflammatory factors synthesis in osteoarthritis synovial fibroblasts by suppressing the PI3K, Akt, and mTOR pathways and activating miR-5006-5p

Betulin inhibits inflammatory factors synthesis in osteoarthritis synovial fibroblasts by suppressing the PI3K, Akt, and mTOR pathways and activating miR-5006-5p

  • Int J Med Sci. 2026 Mar 17;23(4):1567-1576. doi: 10.7150/ijms.130493.
Kun-Tsan Lee 1 2,  Chun-Hao Tsai 3 4,  Yu-Han Wang 5,  Xiu-Yuan He 5,  Yi-Chin Fong 3 4 6,  Chih-Yuan Ko 3,  Chih-Hsin Tang 5 7 8
Affiliations

Affiliations

  • 1 Department of Post-Baccalaureate Medicine, National Chung-Hsing University, Taichung, Taiwan.
  • 2 Department of Orthopedics Surgery, Taichung Veterans General Hospital, Taichung, Taiwan.
  • 3 Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
  • 4 Department of Sports Medicine, College of Health Care, China Medical University, Taichung, Taiwan.
  • 5 Department of Pharmacology, School of Medicine, China Medical University, Taichung, Taiwan.
  • 6 Department of Orthopedic Surgery, China Medical University Beigang Hospital, Yunlin, Taiwan.
  • 7 Department of Medical Laboratory Science and Biotechnology, College of Medical and Health Science, Asia University, Taichung, Taiwan.
  • 8 Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.
PMID: 41938515 DOI: 10.7150/ijms.130493
Abstract

Osteoarthritis (OA) is a widespread joint condition often linked to aging and obesity, resulting in pain, joint dysfunction, and disability. Betulin, a lupane-type pentacyclic triterpene alcohol extracted from birch trees, exhibits anti-inflammatory properties; however, its anti-inflammatory effects in OA remain largely unknown. Our high-throughput cytokine array data exhibit that betulin inhibits two key inflammatory factors, CHI3L1 and ICAM-1, in OA synovial fibroblasts (OASFs). Results from the GEO database and our clinical tissues confirm that CHI3L1 and ICAM-1 levels are markedly higher in OA patients compared to healthy individuals. Furthermore, anterior cruciate ligament transection (ACLT)-induced OA rats exhibited upregulated CHI3L1 and ICAM-1 expression. Mechanistically, we demonstrated that betulin inhibits CHI3L1 and ICAM-1 synthesis in OASFs by inhibiting the PI3K, Akt, and mTOR pathways and activating miR-5006-5p. Importantly, molecular docking analysis predicted an interaction between betulin with CHI3L1 and ICAM-1, suggesting its direct effects. Our investigation suggests that betulin is a leading candidate for OA management.

Keywords

Betulin; CHI3L1; ICAM-1; Osteoarthritis.

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