Secalonic acid A protects dopaminergic neurons from 1-methyl-4-phenylpyridinium (MPP⁺)-induced cell death via the mitochondrial apoptotic pathway.

Abstract

Secalonic acid A (SAA) is a natural compound found in marine fungi. We have reported that SAA can attenuate the cytotoxicity of colchicine in rat cortical neurons. Whether SAA can also inhibit the neurotoxicity of 1-methyl-4-phenylpyridinium (MPP(+)) in dopaminergic neurons has not been investigated. Here, we show that pretreatment with 1 μM SAA significantly rescued tyrosine hydroxylase (TH)-positive neurons from MPP(+)-induced neurotoxicity in primary dopaminergic neuron culture. Moreover, SAA at doses of 0.15 mg/kg and 0.75 mg/kg increased the number of dopaminergic neurons and upregulated striatal dopamine in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced Parkinson's disease mice experiments. We also show that SAA significantly attenuated cytotoxicity induced by 2.5 mM MPP(+) in SH-SY5Y cells. These results indicate that the activation of JNK, p38 mitogen activated protein kinase (MAPK) and caspase-3 during apoptosis triggered by MPP(+) could be suppressed by SAA; on the other hand, an MPP(+)-induced increase in the expression of Bax in SH-SY5Y cells was blocked by SAA. These results indicate that inhibition of the phosphorylation of JNK and p38 MAPK, down-regulation of Bax expression, and suppression of caspase-3 activation are involved in the protective effects of SAA against MPP(+) toxicity in SH-SY5Y cells. SAA may rescue dopaminergic neurons from MPP(+)-induced cell death through the mitochondrial apoptotic pathway.

• Authors: Aifeng Zhai, Xiaonan Zhu, Xuelan Wang, Ruzhu Chen, Hai Wang
• Journal: European journal of pharmacology (Eur J Pharmacol) Vol. 713 Issue 1-3 Pg. 58-67 (Aug 05 2013) ISSN: 1879-0712 [Electronic] Netherlands
• PMID: 23665112 (Publication Type: Journal Article)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Neuroprotective Agents
• Xanthones
• secalonic acid
• 1-Methyl-4-phenylpyridinium

Topics

• 1-Methyl-4-phenylpyridinium (toxicity)
• Animals
• Apoptosis (drug effects)
• Cell Death (drug effects)
• Cell Line
• Dopaminergic Neurons (drug effects, metabolism, pathology)
• Female
• MPTP Poisoning (drug therapy, metabolism, pathology)
• Male
• Mesencephalon (cytology, embryology)
• Mice
• Mice, Inbred C57BL
• Mitochondria (drug effects, metabolism, pathology)
• Neuroprotective Agents (administration & dosage, pharmacology, therapeutic use)
• Pregnancy
• Primary Cell Culture
• Rats
• Rats, Sprague-Dawley
• Substantia Nigra (cytology)
• Xanthones (administration & dosage, pharmacology, therapeutic use)