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Myricitrin Alleviates Methylglyoxal-Induced Mitochondrial Dysfunction and AGEs/RAGE/NF-κB Pathway Activation in SH-SY5Y Cells

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Abstract

Advanced glycation end products (AGEs) have been identified in age-related intracellular protein deposits of neurodegenerative diseases. Methylglyoxal (MGO), a dicarbonyl metabolite, is a major precursor of AGEs which have been linked to the development of neurodegenerative diseases. Myricitrin, a flavanoid isolated from the root bark of Myrica cerifera, attenuated 6-OHDA-induced mitochondrial dysfunction and had a potential anti-Parkinson’s disease in our previous investigation. The aims of this study were to investigate the protective effects of myricitrin against MGO-induced injury in SH-SY5Y cells and also to look for the possible mechanisms. The results showed that exposure of SH-SY5Y cells to MGO caused decreases of cell viability, intracellular ATP, mitochondrial redox activity, and mitochondrial membrane potential and an increase in reactive oxygen species generation. However, these mitochondrial dysfunctions were alleviated by co-treatment with myricitrin. Additionally, myricitrin was capable of inhibiting AGEs formation, blocking RAGE expression, and inhibiting NF-κB activation and translocation triggered by MGO in SH-SY5Y cells. Our results suggest that myricitrin alleviates MGO-induced mitochondrial dysfunction, and the possible mechanism is through modulating the AGEs/RAGE/NF-κB pathway. In summary, myricitrin might offer a promising therapeutic strategy to reduce the neurotoxicity of reactive dicarbonyl compounds, providing a potential benefit agent with age-related neurodegenerative diseases.

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Acknowledgments

This research was supported by grants from the National Natural Science Foundation of China (30973889), Science and Technology Major Projects: significant new-drugs creation (2012ZX09103101-078; 2012ZX09103201-042; 2011ZX09401-014), and the Research Special Fund for Public Welfare Industry of Health (200902008).

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Authors and Affiliations

  1. National Key Research Laboratory of Natural and Biomimetic Drugs, Peking University, Beijing, China

    Yue-Hua Wang & Xiao-Ping Pu

  2. Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing, China

    Yue-Hua Wang & Xiao-Ping Pu

  3. Beijing Key Laboratory of Drug Target Identification, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Yue-Hua Wang & Guan-Hua Du

  4. State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China

    Yue-Hua Wang & Guan-Hua Du

  5. Jiangsu Kanon Pharmaceutical Co., Ltd, Lianyungang, Jiangsu Province, China

    Hai-Tao Yu

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  1. Yue-Hua Wang
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  2. Hai-Tao Yu
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Correspondence to Xiao-Ping Pu or Guan-Hua Du.

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Wang, YH., Yu, HT., Pu, XP. et al. Myricitrin Alleviates Methylglyoxal-Induced Mitochondrial Dysfunction and AGEs/RAGE/NF-κB Pathway Activation in SH-SY5Y Cells. J Mol Neurosci 53, 562–570 (2014). https://doi.org/10.1007/s12031-013-0222-2

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