Catalpol protects mesencephalic neurons against MPTP induced neurotoxicity via attenuation of mitochondrial dysfunction and MAO-B activity.

Abstract

Catalpol, an iridoid glucoside, separated from the root of Rehmannia glutinosa Libosch, has been known to show various neuroprotective effects. In humans and rodents, MPTP is well known to produce clinical, biochemical and neurochemical changes similar to those which occur in Parkinson's disease (PD). Furthermore, the accumulated evidence suggests that MPP(+), conversed by monoamine oxidase type B (MAO-B) in astrocytes principally, is the active metabolite of MPTP and the major cause to PD associated with mitochondrial dysfunction. In this study, we treated mesencephalic neuron-astrocyte and astrocytes cultures with MPTP (0.05 mM) respectively to investigate the neuroprotective effects of catalpol and the underlying protective mechanisms. Our results showed that pre-treatment with catalpol (0.5mM) for 1h prior to MPTP treatment attenuated mitochondrial dysfunction not only by reversing the activity of mitochondrial complex I, mitochondrial membrane potential (MMP), intracellular Ca(2+) level, and ROS accumulation as well as mitochondrial permeability transition (MPT) pore opening in mesencephalic neuron-astrocyte cultures, but also inhibiting MAO-B activity to protect neurons from more MPP(+) toxicity produced in astrocytes. Together, all of these indicated that catalpol possesses potent neuroprotective activity and may be a potential anti-PD drug worthy for further study.

• Authors: Jing Bi, Xiao-Bo Wang, Lei Chen, Shuang Hao, Li-Jia An, Bo Jiang, Lei Guo
• Journal: Toxicology in vitro : an international journal published in association with BIBRA (Toxicol In Vitro) Vol. 22 Issue 8 Pg. 1883-9 (Dec 2008) ISSN: 0887-2333 [Print] England
• PMID: 18840519 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucosides
• Iridoid Glucosides
• Iridoids
• Mitochondrial Membrane Transport Proteins
• Mitochondrial Permeability Transition Pore
• Neuroprotective Agents
• Reactive Oxygen Species
• catalpol
• Monoamine Oxidase
• Calcium

Topics

• Animals
• Astrocytes (drug effects, metabolism)
• Calcium (metabolism)
• Cells, Cultured
• Glucosides (isolation & purification, pharmacology)
• Iridoid Glucosides
• Iridoids (isolation & purification, pharmacology)
• MPTP Poisoning (physiopathology, prevention & control)
• Membrane Potential, Mitochondrial (drug effects)
• Mesencephalon (drug effects, pathology)
• Mice
• Mitochondrial Membrane Transport Proteins (drug effects, metabolism)
• Mitochondrial Permeability Transition Pore
• Monoamine Oxidase (drug effects, metabolism)
• Neurons (drug effects, pathology)
• Neuroprotective Agents (isolation & purification, pharmacology)
• Neurotoxicity Syndromes (etiology, prevention & control)
• Reactive Oxygen Species (metabolism)
• Rehmannia (chemistry)