2. Academic Validation
  3. Wogonin ameliorates osteoarthritis by targeting the STAT3/PIM1 axis to attenuate chondrocyte senescence

Wogonin ameliorates osteoarthritis by targeting the STAT3/PIM1 axis to attenuate chondrocyte senescence

  • Phytomedicine. 2026 Apr:153:157986. doi: 10.1016/j.phymed.2026.157986.
Meiling Yuan 1,  Xinyue Zhou 1,  Wenbo Xu 2,  Jingfeng Liu 3,  Tao Han 3,  Yurong Huang 4,  Faxue Liao 3,  Jun Chang 5,  Chenggui Miao 6
Affiliations

Affiliations

  • 1 Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Anhui University of Chinese Medicine, Hefei, 230012, Anhui, China; Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, 230012, Anhui, China.
  • 2 Orthopedics Department, Ma'anshan Traditional Chinese Medicine Hospital, Anhui University of Chinese Medicine, Ma'anshan, 243000, Anhui, China.
  • 3 Department of Orthopaedics, The First Affiliated Hospital, Anhui Public Health Clinical Center, Anhui Medical University, Hefei, China.
  • 4 Center of Infectious Diseases and Pathogen Biology, State Key Laboratory for Diagnosis and Treatment of Severe Zoonotic Infectious Diseases, The First Hospital, Jilin University, Changchun 130021, China.
  • 5 Department of Orthopaedics, The First Affiliated Hospital, Anhui Public Health Clinical Center, Anhui Medical University, Hefei, China. Electronic address: [email protected].
  • 6 Center for Xin'an Medicine and Modernization of Traditional Chinese Medicine of IHM, Anhui University of Chinese Medicine, Hefei, 230012, Anhui, China; Department of Pharmacology, School of Integrated Chinese and Western Medicine, Anhui University of Chinese Medicine, Hefei, 230012, Anhui, China; Institute of Prevention and Treatment of Rheumatoid Arthritis, Anhui University of Chinese Medicine, Hefei, 230012, Anhui, China. Electronic address: [email protected].
PMID: 41722125 DOI: 10.1016/j.phymed.2026.157986
Abstract

Background: Wogonin, a flavonoid component derived from Scutellaria baicalensis Georgi roots, exerts considerable therapeutic efficacy against osteoarthritis (OA), yet with unclear precise mechanism.

Purpose: To investigate the therapeutic effect of Wogonin on OA and clarify its potential mechanisms.

Methods: IL-1β-induced C28/I2 cells and mice undergoing destabilization of the medial meniscus (DMM) were constructed to simulate OA. The curative effect of Wogonin was evaluated using pathological staining, micro-CT, Tunel, EdU and migration assay. The repair effect of Wogonin on cartilage injury was assessed by immunohistochemistry, immunofluorescence, toluidine blue and SA-β-gal. The interaction potency between Wogonin and its target protein was validated using RNA-Seq, molecular dynamics simulations (MDs), surface plasmon resonance (SPR), cellular thermal shift assay (CETSA) and drug affinity responsive target stability (DARTS). The mechanism by which Wogonin modulated OA was validated using STAT3 agonist and pcDNA3.1-STAT3.

Results: Wogonin could ameliorate articular cartilage injury, inhibit synovitis and osteophyte formation in DMM mice, promote the proliferation and hinder Apoptosis of IL-1β-induced C28/I2 cells. Wogonin could suppress matrix degradation, stimulate matrix synthesis and proteoglycan secretion, enhance CDK and Cyclin transcriptional levels, concomitantly retarded SA-β-gal, senescence-associated secretory phenotype (SASP), γ-H2A.X, P16, P21 and P53. Mechanistically, STAT3 was a direct target of Wogonin. Upregulation of STAT led to significantly increased p-STAT3/STAT3 and PIM1 expression, and simultaneously aggravated cartilage injury and cell senescence. In contrast, Wogonin inhibited its activation by directly binding STAT3 and reversed the above pathological changes.

Conclusion: Wogonin could inhibit chondrocyte senescence, reduce cartilage damage and alleviate OA by targeting the STAT3/PIM1 axis.

Keywords

C28/I2; Cartilage injury; Osteoarthritis; Senescence; The STAT3/PIM1 axis; Wogonin.

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