Network analysis and experimental validation analysis reveal the mechanism by which psoralen improves

Wenxiang Zeng1, Ying Zhao2, Qingyu Tu1

  • 1The Third Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou 310053, China; Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou 311200, China.

Insights

Psoralen (PSO) may treat glucocorticoid-induced growth retardation (GIGR) in children. This study found PSO enhances growth plate chondrocyte proliferation and bone growth by activating the PI3K/AKT pathway, offering a potential therapeutic strategy.

Area of Science:

  • Pharmacology
  • Endocrinology
  • Cell Biology

Background:

  • Glucocorticoids (GCs) are widely used medications with significant side effects, including growth retardation in pediatric patients.
  • GC-induced growth retardation (GIGR) negatively impacts skeletal development by inhibiting endochondral ossification in growth plate chondrocytes.
  • Psoralen (PSO) has demonstrated potential in preserving cartilage homeostasis and enhancing chondrocyte proliferation, but its mechanisms against GIGR are not fully understood.

Purpose of the Study:

  • To investigate the therapeutic potential of psoralen (PSO) in mitigating glucocorticoid-induced growth retardation (GIGR).
  • To elucidate the underlying molecular mechanisms by which PSO affects GC-damaged growth plate chondrocytes.

Main Methods:

  • Network pharmacology and molecular docking were employed to identify potential therapeutic targets of PSO.
  • Experimental validation in a rat model and in vitro cell cultures assessed PSO's effects on growth plate chondrocytes.
  • Western blotting and immunofluorescence were used to analyze protein expression and signaling pathway activation.

Main Results:

  • PSO treatment significantly increased femoral length and growth plate size in rats compared to controls.
  • In vitro studies showed PSO enhances growth plate chondrocyte proliferation and maintains cellular homeostasis.
  • PSO activated the PI3K/AKT signaling pathway, increased cartilage-related protein expression, and reduced apoptotic protein levels.

Conclusions:

  • Psoralen (PSO) demonstrates a protective effect against GC-induced damage in growth plate chondrocytes.
  • PSO promotes skeletal growth and chondrocyte proliferation by activating the PI3K/AKT signaling pathway.
  • PSO represents a promising therapeutic candidate for managing GC-induced growth retardation (GIGR).

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