The discovery of the new mechanism: Celastrol improves spinal cord injury by increasing cAMP through VIP-ADCYAP1R1-GNAS pathway

Biomed Pharmacother. 2023 Sep:165:115250. doi: 10.1016/j.biopha.2023.115250. Epub 2023 Jul 31.

Abstract

Spinal cord injury (SCI) is a debilitating condition that results in significant impairment of motor function and sensation. Despite the ongoing efforts to develop effective treatments, there are currently very limited options available for patients with SCI. Celastrol, a natural anti-inflammatory compound extracted from Tripterygium wilfordii, has been shown to exhibit anti-inflammatory and anti-apoptotic properties. In this study, we aimed to explore the therapeutic potential of celastrol for SCI and elucidate the underlying molecular mechanisms involved. We found that local tissue often experiences a significant decrease in cAMP content and occurrs apoptosis after SCI. However, the treatment of celastrol could promote the production of cAMP by up-regulating the VIP-ADCYAP1R1-GNAS pathway. This could effectively inhibit the phosphorylation of JNK and prevent apoptosis, ultimately improving the exercise ability after SCI. Together, our results reveal celastrol may be a promising therapeutic agent for the treatment of SCI.

Keywords: Apoptosis; Celastrol; JNK; Spinal cord injury; VIP; cAMP.

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Apoptosis
  • Chromogranins / pharmacology
  • Chromogranins / therapeutic use
  • GTP-Binding Protein alpha Subunits, Gs / pharmacology
  • GTP-Binding Protein alpha Subunits, Gs / therapeutic use
  • Pentacyclic Triterpenes / pharmacology
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Spinal Cord
  • Spinal Cord Injuries* / drug therapy
  • Triterpenes* / pharmacology
  • Triterpenes* / therapeutic use

Substances

  • Anti-Inflammatory Agents
  • celastrol
  • Chromogranins
  • GTP-Binding Protein alpha Subunits, Gs
  • Pentacyclic Triterpenes
  • Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide, Type I
  • Triterpenes