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Chrysophanol Relieves Cognition Deficits and Neuronal Loss Through Inhibition of Inflammation in Diabetic Mice

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Abstract

Patients with diabetes mellitus are easy to experience diabetic encephalopathy (DE) and other cognition dysfunction, whereas the neural alterations in developing this disease are unknown yet. Chrysophanol (CHR) is one of traditional Chinese medicine which was reported to show protective effects in cognition dysfunction and inflammatory in previously studies. In this current study, whether CHR protects learning and memory dysfunctions induced by diabetes disease or not and underlying mechanisms were studied. DE model was induced by streptozotocin (STZ, i.p.) in ICR mice. CHR was administrated 3 days after STZ treated mice which was confirmed with diabetes for consecutive 6 days. Learning and memory function was tested by Morris water maze after the CHR injection. The morphology of neuronal cells in hippocampus CA3 region was stained by HE-staining. ELISA and Western blot assay were used to determine the levels of pro-inflammation cytokines (IL-1β, IL-4, IL-6, TNF-α) in hippocampus. Here, we demonstrated that mice harboring diabetes mellitus induced by STZ exhibit high blood glucose, learning and memory deficits detected by Morris water maze behavior tests. Application with CHR right after developing diabetes disease rescues partial blood sugar increasing, learning and memory deficits. The data also indicated that the death rate of neurons and the number of astrocytes in hippocampus CA3 region was significantly improved in diabetic mice. Moreover, the underlying mechanisms of CHR’s protective effect are likely associated with anti-inflammation by downregulating the expression of pro-inflammation cytokines (IL-1β, IL-4, IL-6, TNF-α) in hippocampus and inhibiting the over-activation of astrocytes in hippocampus CA3 region. Therefore, application with CHR contributes to the learning and memory deficits induced by diabetes disease via inhibitory expressions of inflammatory in hippocampus region.

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Abbreviations

DE:

Diabetic encephalopathy

CHR:

Chrysophanol

STZ:

Streptozotocin

AD:

Alzheimer disease

IL:

Interleukin

TNF-α:

Tumor necrosis factor

CA3:

Cornu ammonis

MWM:

Morris water maze

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Acknowledgements

This work was supported by Science and Technology development Plan of Jining city (JKZ[2015]57-94).

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Authors and Affiliations

  1. Department of Neurology, Affiliated Hospital of Jining Medical University, 89 Guhuai Road, Jining, 272000, Shandong, People’s Republic of China

    Xu Chu, Shuhu Zhou, Ran Sun, Lin Wang, Chunye Xing, Ruqing Liang & Qingxia Kong

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  1. Xu Chu
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  2. Shuhu Zhou
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  3. Ran Sun
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  4. Lin Wang
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  5. Chunye Xing
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  6. Ruqing Liang
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  7. Qingxia Kong
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Contributions

QK designed the study. XC, SZ, RS, LW, and CX performed the experiments and collected the data. XC, SZ, and RS analyzed and interpreted the experimental data. XC and CX prepared the manuscript.

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Correspondence to Qingxia Kong.

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Chu, X., Zhou, S., Sun, R. et al. Chrysophanol Relieves Cognition Deficits and Neuronal Loss Through Inhibition of Inflammation in Diabetic Mice. Neurochem Res 43, 972–983 (2018). https://doi.org/10.1007/s11064-018-2503-1

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  • DOI: https://doi.org/10.1007/s11064-018-2503-1

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