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Suppression of methylglyoxal hyperactivity by mangiferin can prevent diabetes-associated cognitive decline in rats

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Abstract

Rationale

Evidences indicate that methylglyoxal, a highly reactive metabolite of hyperglycemia, can enhance protein glycation, oxidative stress, or inflammation. Mangiferin, a polyphenol compound of C-glucoside, has many beneficial biological activities, including anti-inflammation, anti-oxidation, neuroprotection, cognitive enhancement, etc. Whether mangiferin alleviates diabetes-associated cognitive impairment is still unclear.

Objectives

The present study was designed to investigate the effects of mangiferin on the behavioral deficits of diabetic rats induced by streptozotocin; the mechanisms associated with methylglyoxal toxicity are especially investigated.

Methods

Diabetic rats were treated with mangiferin (15, 30, and 60 mg/kg, p.o.) for 9 weeks. Cognitive performances were evaluated with the Morris water maze. Hippocampus and blood were obtained for evaluation of the effects of mangiferin on protein glycation, oxidative stress, and inflammation in diabetic state.

Results

Mangiferin significantly improved the behavioral performances of diabetic rats, evidenced by a decrease in escape latency as well as increases in numbers of crossing the platform and percentage of time spent in the target quadrant, which were accompanied by decreases in the levels of advanced glycation end-products and their receptor (RAGE), interleukin-1β, TNF-α, and malondialdehyde and increases in the activity and expression of glyoxalase 1 as well as glutathione level in the hippocampus of diabetic rats. Furthermore, mangiferin produced a significant decrease in malondialdehyde level and increased glutathione level and superoxide dismutase activity in the serum of diabetic rats.

Conclusions

This study demonstrates that mangiferin can markedly ameliorate diabetes-associated cognitive decline in rats, which is done likely through suppressing methylglyoxal hyperactivity (promoting protein glycation, oxidative stress, and inflammation) mediated noxious effects.

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Acknowledgment

The work was supported by the Natural Science Foundation of Jiangsu Province (BK2011208), China, China Postdoctoral Science Foundation (201150M1576), and a project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD), China. The experiments comply with the current laws of the People’s Republic of China.

Conflict of interest

The authors have declared that there is no conflict of interest.

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Authors and Affiliations

  1. Key Laboratory of New Drugs and Clinical Application, Xuzhou Medical College, No. 209, Tongshan Road, Xuzhou, 221004, Jiangsu, China

    Yao-Wu Liu, Xia Zhu, Qian-Qian Yang, Qian Lu, Jian-Yun Wang, Hui-Pu Li, Ya-Qin Wei, Jia-Le Yin & Xiao-Xing Yin

  2. Department of Pharmacology, Nanjing General Hospital of Nanjing Military Command, Nanjing, 210002, Jiangsu, China

    Yao-Wu Liu & Xiao-Xing Yin

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  1. Yao-Wu Liu
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  2. Xia Zhu
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Corresponding author

Correspondence to Xiao-Xing Yin.

Additional information

Yao-Wu Liu and Xia Zhu contributed equally to this project.

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Liu, YW., Zhu, X., Yang, QQ. et al. Suppression of methylglyoxal hyperactivity by mangiferin can prevent diabetes-associated cognitive decline in rats. Psychopharmacology 228, 585–594 (2013). https://doi.org/10.1007/s00213-013-3061-5

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  • DOI: https://doi.org/10.1007/s00213-013-3061-5

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