Articles
Vol. 70 No. 4 (2026)
Sinensetin ameliorates osteoarthritis progression by modulating the NF-κB/NLRP3 signaling pathway and suppressing chondrocyte pyroptosis
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All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.
Published: 7 October 2026
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Sinensetin (SIN) is a natural flavonoid with potential anti‑inflammatory effects. This study investigated whether SIN ameliorates osteoarthritis (OA) and explored its underlying mechanisms. In vitro, SIN (0.05-1 μg/mL) protected human OA chondrocytes from IL‑1β‑induced viability loss. Transcriptome sequencing and molecular docking identified SERPINA3 as a candidate target of SIN. SIN reduced the expression of NLRP3, GSDMD, and ASC, inhibited pyroptotic morphology, decreased TUNEL‑positive cells and LDH release, and lowered IL‑1β and IL‑18 secretion in IL‑1β‑treated chondrocytes. Knockdown of SERPINA3 reversed these effects, suggesting that SIN acts through SERPINA3 to inhibit the NLRP3 inflammasome. In a rat DMM‑induced OA model, SIN (20 mg/kg/day for 6 weeks) alleviated pain, reduced OARSI scores, improved cartilage matrix staining (Safranin O, Masson's trichrome), attenuated synovial hyperplasia and posterior capsule adhesions, and decreased plasma IL‑1β and IL‑18 levels. Western blot of rat cartilage confirmed that SIN suppressed GSDMD and NLRP3 expression. These results indicate that SIN ameliorates OA progression by inhibiting SERPINA3‑mediated NF‑κB/NLRP3‑driven chondrocyte pyroptosis. SIN may be a potential therapeutic candidate for OA.
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CRediT authorship contribution
Zhendong Liu, investigation, methodology, writing – original draft. Ruizhou Liu, resources, writing – review and editing. Hongwei Yue, data curation, visualization, methodology, validation. Peilai Liu, conceptualization, project administration, writing – review and editing. Rui Wang, data curation, formal analysis, conceptualization.
Supporting Agencies
This work was supported by the Shandong Province Traditional Chinese Medicine Science & Technology Project (Grant No. M20241309).Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request. The datasets generated and/or analysed during the current study are available in the ICPSR repository (NAHDAP‑223101).
How to Cite
1.
Liu Z, Liu R, Yue H, Liu P, Wang R. Sinensetin ameliorates osteoarthritis progression by modulating the NF-κB/NLRP3 signaling pathway and suppressing chondrocyte pyroptosis. Eur J Histochem [Internet]. 2026 Oct. 7 [cited 2026 Oct. 7];70(4). Available from: https://www.ejh.it/ejh/article/view/4587
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