Paeoniflorin modulates DL-glyceraldehyde metabolism to promote mitochondrial dynamics homeostasis and ameliorate knee osteoarthritis cartilage degeneration

  • Phytomedicine. 2026 Jul:156:158211. doi: 10.1016/j.phymed.2026.158211.
Zugui Wu  1 ,  Yue Zhu  2 ,  Rong Yuan  3 ,  Yuanlong Li  4 ,  Jiao Li  3 ,  Bo Qiao  5 ,  Zhiwei Wu  3 ,  Yanfei Xu  3 ,  Yu Zhang  6 ,  Wei Dong  7 ,  Ying Guo  8 ,  Xuemeng Xu  9
Affiliations
  • 1. The Third Clinical College of Yunnan University of Chinese Medicine, Kunming 650500, China; Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510000, China; College of Basic Medicine, Yunnan University of Chinese Medicine, Yunnan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Kunming 650500, China.
  • 2. The Third Clinical College of Yunnan University of Chinese Medicine, Kunming 650500, China; College of Basic Medicine, Yunnan University of Chinese Medicine, Yunnan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Kunming 650500, China.
  • 3. The Third Clinical College of Yunnan University of Chinese Medicine, Kunming 650500, China.
  • 4. Sun Yat-Sen University, Guangzhou 510120, China.
  • 5. College of Basic Medicine, Yunnan University of Chinese Medicine, Yunnan Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Chronic Disease in Prevention and Treatment, Kunming 650500, China.
  • 6. Guangdong Cardiovascular Institute, Guangdong Academy of Medical Sciences, Southern Medical University, Guangzhou 510000, China.
  • 7. The Third Clinical College of Yunnan University of Chinese Medicine, Kunming 650500, China. Electronic address: [email protected].
  • 8. The Third Clinical College of Yunnan University of Chinese Medicine, Kunming 650500, China. Electronic address: [email protected].
  • 9. The Fifth Clinical Medical College of Guangzhou University of Chinese Medicine, Guangzhou 510006, China. Electronic address: [email protected].
PMID: 42068874 DOI: 10.1016/j.phymed.2026.158211
Abstract

Background: Knee osteoarthritis (KOA) is a common chronic degenerative joint disease, and its primary pathological feature of articular cartilage is degeneration. Paeniflorin, a bioactive terpene glycoside isolated from Paeonia lactiflora, has demonstrated a protective effect on chondrocytes, but its specific mechanism are not well understood.

Purpose: The study aimed to clarify the molecular mechanism by which paeoniflorin enhances cartilage repair and metabolic functions.

Methods: The effects of paeoniflorin on chondrocyte were evaluated using cell staining (toluidine blue and Alcian blue), flow cytometry, PCR, Western blotting, and immunofluorescence. A destabilization of the medial meniscus (DMM) -induced rat model with KOA was established. Micro-Computed Tomography, histopathological staining, and immunohistochemistry were used to assess cartilage repair and metabolic changes. Additionally, transcriptomic and metabolomic analyses were conducted to evaluate the effects of paeoniflorin on mitochondrial dynamics-related genes and their differential metabolites. Molecular docking experiments were used to verify these targets.

Results: The in vitro experiments demonstrated that paeoniflorin markedly enhanced the proliferative activity of chondrocytes, and reduced the Apoptosis rate. in vivo experiments, paeoniflorin intervention significantly improved bone volume and structural parameters of the subchondral bone in rats with KOA and facilitated the repair of cartilage damage. Combined transcriptomic and metabolomic analyses revealed that paeoniflorin promoted mitochondrial homeostasis by regulating DL-glyceraldehyde (DLG), thereby improving chondrocyte energy metabolism. Molecular docking, molecular dynamics simulations, and downstream mechanistic study indicated that paeoniflorin regulated the expression of mitochondrial dynamics-related genes by modulating DLG levels, promoting mitochondrial fusion, and inhibiting excessive fission.

Conclusion: Paeoniflorin effectively ameliorated cartilage degeneration in KOA by modulating the downstream metabolite DLG to promote mitochondrial dynamic homeostasis.

Keywords
Cartilage degeneration; Knee osteoarthritis; Metabolomics; Mitochondrial dynamics; Paeoniflorin; Transcriptomics.
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