The therapeutic potential of triptolide and celastrol in neurological diseases

Neurological diseases are complex disorders affecting the brain and spinal cord, with incompletely understood causes. Triptolide and celastrol, from Tripterygium wilfordii Hook. F. (TWHF), possess anti-inflammatory, immunosuppressive, and anti-tumor effects, showing potential in treating neurological diseases. This review summarizes preclinical studies of triptolide and celastrol in neurological diseases like neurodegenerative disorders, brain/spinal cord injuries, and epilepsy. It explores their mechanisms, toxicity, derivatives, and nanotechnology-based delivery. Triptolide and celastrol, because of their small molecular weight and lipophilicity, can cross the blood-brain barrier and work in the brain, so they have been studied in many neurological diseases.

• 1
  Triptolide and celastrol exhibit therapeutic effects in Alzheimer's disease by inhibiting Aβ deposition, reducing neuroinflammation, decreasing ROS levels, attenuating apoptosis, enhancing autophagy, and exerting neurotrophic effects.
• 2
  In Parkinson's disease models, triptolide and celastrol attenuate neuroinflammation, promote α-synuclein clearance, and exert neurotrophic effects, suggesting their potential as clinical treatments.
• 3
  Both triptolide and celastrol demonstrate neuroprotective effects in multiple sclerosis models by inhibiting NF-kB activity, modulating Th1/Th2 cytokine profiles, and suppressing Th17 cell responses, thereby attenuating neuroinflammation.