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Protective effects of isofraxidin against scopolamine-induced cognitive and memory impairments in mice involve modulation of the BDNF-CREB-ERK signaling pathway

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Abstract

Background

Isofraxidin is a coumarin compound mainly isolated from several traditional and functional edible plants beneficial for neurodegenerative diseases, including Sarcandra glabra and Apium graveolens, and Siberian Ginseng.

Objective

This study aimed to assess effects of isofraxidin against memory impairments and cognition deficits in a scopolamine-induced mouse model.

Materials & methods

Animals were randomly divided into 6 groups, control, vehicle, donepezil (10 mg/kg, p.o.), and isofraxidin (3, 10, and 30 mg/kg, p.o.). Isofraxidin or donepezil was administered for 44 days, once per day. The scopolamine insults (1 mg/kg, i.p.) was given from the 21st day, once per day. Morris water maze test and Y-maze test were used for the behavioral test. After that, brain samples were collected for analysis.

Results

Firstly, isofraxidin significantly improved scopolamine-induced behavioral impairments and cognition deficits in Morris water maze and Y-maze test. Then, isofraxidin facilitated cholinergic activity via inhibiting acetylcholinesterase (AChE) activity. Besides, isofraxidin decreased lipid peroxidation level but enhanced levels of glutathione, glutathione peroxidase, and superoxide dismutase. Moreover, isofraxidin suppressed the expression of inflammatory mediators and cytokines. Further investigations showed that isofraxidin up-regulated expression of brain-derived neurotrophic factor (BDNF), and promoted phosphorylation of tropomyosin-related kinase B (TrkB), cyclic AMP-response element-binding protein (CREB), and extracellular signal-regulated kinase (ERK).

Discussion & Conclusions

These results suggested that isofraxidin ameliorated scopolamine-induced cognitive and memory impairments, possibly through regulating AChE activity, suppressing oxidative stress and inflammatory response, and modulating BDNF-CREB-ERK pathways.

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Data availability statement

The data that support the findings of this study are available on requests from the corresponding authors.

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Acknowledgements

This work is supported in part by the National Natural Science Foundation of China (82003615), the National Key R&D Program of China (2018YFA0800603), the Key Research and Development Program of Guangdong Province for “Innovative drug creation” (2019B020201015), and the Guangdong Innovative Research Team Program (2016ZT06Y432).

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Authors and Affiliations

  1. The School of Biomedical and Pharmaceutical Sciences, Guangdong University of Technology, Guangzhou, China

    Bingliang Lian, Jingwen Gu, Chen Zhang, Fanghong Li, Xiaoli Wu & Allan Zijian Zhao

  2. School of Pharmaceutical Sciences, Guangzhou Medical University, Guangzhou, China

    Zhicong Zou & Meng Yu

Authors
  1. Bingliang Lian
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  2. Jingwen Gu
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  3. Chen Zhang
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  4. Zhicong Zou
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  5. Meng Yu
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  6. Fanghong Li
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  7. Xiaoli Wu
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  8. Allan Zijian Zhao
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Contributions

Designed the study: Bingliang Lian and Xiaoli Wu. Performed the experiments:Bingliang Lian, Jingwen Gu, Chen Zhang, Zhicong Zou and Meng Yu. Data collection and Statistical analyses: Bingliang Lian, Jingwen Gu, Chen Zhang, Zhicong Zou and Meng Yu. Wrote the main manuscript text: Bingliang Lian and Xiaoli Wu. Revised the main manuscript text: Fanghong Li and Allan Zijian Zhao. All authors reviewed and approved the manuscript.

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Correspondence to Xiaoli Wu or Allan Zijian Zhao.

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Lian, B., Gu, J., Zhang, C. et al. Protective effects of isofraxidin against scopolamine-induced cognitive and memory impairments in mice involve modulation of the BDNF-CREB-ERK signaling pathway. Metab Brain Dis 37, 2751–2762 (2022). https://doi.org/10.1007/s11011-022-00980-z

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