Inhibitory effect of vanillic acid on methylglyoxal-mediated glycation in apoptotic Neuro-2A cells

Shang Ming Huang, Chin Lin Hsu, Hong Chih Chuang, Ping Hsiao Shih, Chi Hao Wu, Gow Chin Yen*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)


Methylglyoxal is a reactive dicarbonyl compound generated as an intermediate of glycolysis during the physical glycation in the diabetic condition. It is considered to be a potent precursor of advanced glycation end products (AGEs) formation. Methylglyoxal itself and methylglyoxal-derived AGEs have been commonly implicated in the development of diabetic neuropathy. Our previous study indicated that vanillic acid showed an inhibitory effect against methylglyoxal-mediated Neuro-2A cell apoptosis, suggesting that vanillic acid might possess cytoprotective properties in the prevention of diabetic neuropathy complication. In this study, the effects of vanillic acid on the methylglyoxal-mediated glycation system involved in the progression of Neuro-2A cell apoptosis were further investigated. Our findings indicated that methylglyoxal-induced Neuro-2A cell apoptosis was mediated through the possible glycation mechanism of oxidative stress, activation of the MAPK signaling pathway (p38 and JNK) and oxidation-sensitive protein expression (PKC and p47phox) and methylglyoxal-derived N-ε-(carboxymethyl)lysine (CML) formation. Vanillic acid, however, suppressed methylglyoxal-induced Neuro-2A cell apoptosis via inhibition of glycation mechanisms including ROS, p38 and JNK, PKC and p47phox, and methylglyoxal-derived CML formation. In the present study, we established the first evidence that vanillic acid might contribute to the prevention of the development of diabetic neuropathy by blocking the methylglyoxal-mediated intracellular glycation system.

Original languageEnglish
Pages (from-to)1016-1022
Number of pages7
Issue number6
Publication statusPublished - 2008 Nov
Externally publishedYes


  • Apoptosis
  • CML
  • Diabetic neuropathy
  • Methylglyoxal
  • Neuro-2A cells
  • Vanillic acid

ASJC Scopus subject areas

  • General Neuroscience
  • Toxicology


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