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Astragaloside IV and echinacoside benefit neuronal properties via direct effects and through upregulation of SOD1 astrocyte function in vitro

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Abstract

Amyotrophic lateral sclerosis (ALS), also known as a major type of motor neuron disease, is a disease characterized by the degeneration of both upper and lower motor neurons. Astragaloside IV (AST) is one of the most effective compounds isolated from Astragalus membranaceus. Echinacoside (ECH) is also an active constituent in Cistanche tubulosa. These two herbs had been used in treating disease described like ALS in ancient China under the guidance of traditional Chinese medicine theory and now they are still being used extensively for ALS in current Chinese medicine practice, but whether AST or ECH has effect on ALS disease condition is still unclear. Survivals of primary cultured neuron and astrocyte were determined by the MTS assay. Proteins including GLT1 and GFAP, from SOD1 G93A Tg (transgenic) astrocyte lysate were determined by Western blot. Synaptic markers, PSD95 and VGLUT1, were stained by immunofluorescence and observed by a confocal microscope. Proper dilution of AST and ECH was confirmed to be not harmful to both astrocytes and neurons. AST and ECH enhanced neuronal synaptic markers density or intensity/area in different aspects. Both AST and ECH could significantly rescue SOD1 astrocyte conditional medium–treated neuronal survival and synapse loss. Ten micromolars ECH could significantly rescue the suppressed GLT1 level expressed by SOD1 Tg astrocyte. This present research proved that AST and ECH could benefit neuronal properties and rescue certain dysfunction, such as GLT1 low expression, loss of neuron-supporting function, of astrocytes under SOD1 condition.

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Acknowledgments

I would like to thank Dr. Men Yuqin from Tufts University who kindly gave me technical assistants and thank Tufts imaging core for providing the confocal microscope.

Funding

This work was supported by the Natural Science Foundation of China (No. 81774250), NATCM TCM Inheritance and Innovation “Hundred-Thousand-Ten Thousand” Talents Project (QiHuang Scholar)—National TCM Leading Personnel Support Program (NATCM Personnel and Education Department [2018] No. 12), and the International Science and Technology Cooperation Program of China (No. 2015DFA31130).

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Authors and Affiliations

  1. Beijing University of Chinese Medicine, Beijing, People’s Republic of China

    Yang Tian

  2. Tufts University School of Medicine, Boston, MA, USA

    Yang Tian, Shijie Jin & Vanessa Promes

  3. Central Laboratory, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China

    Xuemei Liu

  4. Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing, People’s Republic of China

    Yunling Zhang

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  1. Yang Tian
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Contributions

YT, XL, and YZ conceived and designed the research. YT, SJ, and VP conducted the experiments. YT analyzed the data. YT wrote the manuscript. All authors read and approved the manuscript and all data were generated in-house and that no paper mill was used.

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Correspondence to Yunling Zhang.

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The treatment and cares that were performed on animals in all procedures were strictly followed from the NIH Guide for the Care as well as Use of Laboratory Animals and the Guidelines for the Use of Animals in Neuroscience Research. Animal protocols used in this study have been approved by Tufts University IACUC committee.

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Tian, Y., Jin, S., Promes, V. et al. Astragaloside IV and echinacoside benefit neuronal properties via direct effects and through upregulation of SOD1 astrocyte function in vitro. Naunyn-Schmiedeberg's Arch Pharmacol 394, 1019–1029 (2021). https://doi.org/10.1007/s00210-020-02022-w

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