Corynoline Suppresses Osteoclastogenesis and Attenuates ROS Activities by Regulating NF-κB/MAPKs and Nrf2 Signaling

Chen Jin1,2, Xian-Bin Yu1,2, Jiayi Yang3

  • 1Department of Orthopaedic, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou 325000, China.

Insights

Corynoline (Cor), derived from traditional Chinese herbs, effectively inhibits osteoclast formation and bone resorption. This compound shows potential for treating osteoporosis by modulating key signaling pathways and restoring bone mass in preclinical models.

Area of Science:

  • Pharmacology and Traditional Chinese Medicine
  • Bone Biology and Osteoporosis Research
  • Molecular Mechanisms of Disease

Background:

  • Postmenopausal osteoporosis results from an imbalance between bone resorption and formation, driven by declining estrogen.
  • Current osteoporosis treatments have limitations and potential side effects.
  • Corynoline (Cor), an alkaloid from *Corydalis bungeana* Herba, is explored for its therapeutic potential in bone metabolism diseases.

Purpose of the Study:

  • To investigate the effects and underlying mechanisms of Corynoline (Cor) on osteoclast formation and bone resorption.
  • To evaluate Cor's efficacy in an ovariectomized (OVX) mouse model of osteoporosis.

Main Methods:

  • Assessed osteoclast function using Tartrate-resistant acid phosphatase (TRAcP) staining, F-actin belt, and pit formation assays.
  • Analyzed gene expression and signaling pathways via Western blot, qPCR, network pharmacology, and molecular docking.
  • Utilized an OVX mouse model to study Cor's impact on trabecular bone loss, microarchitecture, and reactive oxygen species (ROS) levels.

Main Results:

  • Cor significantly inhibited osteoclast formation and function by modulating the receptor activator of nuclear factor-kappa B (RANKL) pathway.
  • Cor suppressed RANKL-induced NF-κB and MAPK signaling pathways.
  • Cor enhanced Nrf2 protein stability, reducing RANKL-stimulated ROS generation.
  • In OVX mice, Cor restored bone mass, improved microarchitecture, and decreased ROS levels in distal femurs.

Conclusions:

  • Corynoline (Cor) restrains osteoclast formation and bone loss by modulating the NF-κB/MAPKs and Nrf2 signaling pathways.
  • Cor demonstrates potential as a therapeutic agent for osteoporosis treatment.

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