Tribuli Fructus alleviates 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease by suppressing neuroinflammation via JNK signaling

Metab Brain Dis. 2024 Dec 19;40(1):69. doi: 10.1007/s11011-024-01498-2.

Abstract

Parkinson's disease (PD) is a neurodegenerative disease characterized by the loss of dopaminergic neurons. In particular, neuroinflammation associated with phosphorylation of c-Jun N-terminal kinase (JNK) is likely to cause the death of dopaminergic neurons. Therefore, protecting dopaminergic neurons through anti-neuroinflammation is a promising therapeutic strategy for PD. This study investigated whether Tribuli Fructus (TF) could alleviate PD by inhibiting neuroinflammation. Mouse primary mixed glial culture cells from the mouse cortex were treated with lipopolysaccharide (LPS) to induce neuroinflammation, and 1 h later, cells were treated with TF. 1-methyl-4-phenyl 1,2,3,6-tetrahydropyridine (MPTP) was injected into C57BL/6J mice for 5 days, and TF was co and post-administered for 12 days. Our study showed that TF attenuated pro-inflammatory mediators and cytokines in LPS-stimulated primary mixed glial cultures. In the brains of MPTP-induced PD mouse model, TF inhibited the activation of microglia and astrocytes, protected dopaminergic neurons, and increased dopamine levels. TF alleviated MPTP-induced bradykinesia, a representative behavioral disorder in PD. In addition, the results in vitro and in vivo revealed that TF regulates the phosphorylation of JNK. Collectively, our data suggest that TF may be a new therapeutic candidate for PD by regulating JNK signaling.

Keywords: JNK signaling; Mouse primary mixed glial culture; Neuroinflammation; Parkinson’s disease; Tribuli Fructus.

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Astrocytes / drug effects
  • Astrocytes / metabolism
  • Dopaminergic Neurons / drug effects
  • Dopaminergic Neurons / metabolism
  • MAP Kinase Signaling System* / drug effects
  • Male
  • Mice
  • Mice, Inbred C57BL*
  • Microglia / drug effects
  • Microglia / metabolism
  • Neuroinflammatory Diseases* / drug therapy
  • Neuroinflammatory Diseases* / metabolism
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use
  • Parkinsonian Disorders / chemically induced
  • Parkinsonian Disorders / drug therapy
  • Parkinsonian Disorders / metabolism
  • Plant Extracts / pharmacology
  • Plant Extracts / therapeutic use

Substances

  • Neuroprotective Agents
  • Plant Extracts
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine