The protective effects of moscatilin against methylglyoxal-induced neurotoxicity via the regulation of p38/JNK MAPK pathways in PC12 neuron-like cells.

Mei Chou Lai, Wayne Young Liu, Shorong-Shii Liou, I-Min Liu

Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association 2020 Jun

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Methylglyoxal (MGO) is an endogenous toxic compound that plays a vital role in diabetic complications such as diabetic neuropathy. Moscatilin is a bibenzyl component from Dendrobium species, has been shown to possess a wide range of pharmacological activities. To clarify whether moscatilin prevents rat pheochromocytoma cells (PC12 cells) from damage induced by MGO, cells were pre-treated with moscatilin and then stimulated with MGO. Moscatilin inhibited MGO associated cytotoxicity in a concentration (0.1, 0.5, or 1.0 μmol/L)-dependent manner and downregulated the formation of advanced glycation end products and reactive oxygen species. Moscatilin attenuated MGO-induced mitochondrial dysfunction involving the loss of mitochondrial membrane potential and depletion of adenosine triphosphate. MGO induced cell apoptosis via the upregulation of p53, caspases 3 and poly(ADP-ribose)polymerase, enhancement of cytochrome c release, and interruption of the Bax/Bcl-2 balance; these detrimental effects were ameliorated by moscatilin. Furthermore, moscatilin inhibited MGO-induced activation of MAP kinase (MAPK) superfamily, including p38 and c-Jun N-terminal kinases (JNKs). In conclusion, we found that the neuroprotective effect of moscatilin is due to a reduction of MGO-induced damage to mitochondria function through modulating the p38 and JNK stress-activated MAPK cascades pathway. Thus, it might be a potent compound for preventing/counteracting diabetic neuropathy. Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.

Citation

Mei Chou Lai, Wayne Young Liu, Shorong-Shii Liou, I-Min Liu. The protective effects of moscatilin against methylglyoxal-induced neurotoxicity via the regulation of p38/JNK MAPK pathways in PC12 neuron-like cells. Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association. 2020 Jun;140:111369