Astragaloside IV and echinacoside benefit neuronal properties via direct effects and through upregulation of SOD1 astroc
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ORIGINAL ARTICLE
Astragaloside IV and echinacoside benefit neuronal properties via direct effects and through upregulation of SOD1 astrocyte function in vitro Yang Tian 1,2 & Shijie Jin 2 & Vanessa Promes 2 & Xuemei Liu 3 & Yunling Zhang 4 Received: 4 June 2020 / Accepted: 10 November 2020 # Springer-Verlag GmbH Germany, part of Springer Nature 2020
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. Keywords Astragaloside IV . Echinacoside . ALS . Neuronal properties . SOD1 . GLT1
Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder, characterized by weight loss, muscle weakness, limb paralysis, cramps, and fasciculations. This disease ultimately results in the death of patients, mostly due to respiratory compromise. Approximately 50% of patients die within
* Yunling Zhang [email protected]; [email protected] 1
Beijing University of Chinese Medicine, Beijing, People’s Republic of China
2
Tufts University School of Medicine, Boston, MA, USA
3
Central Laboratory, Dongfang Hospital, Beijing University of Chinese Medicine, Beijing, People’s Republic of China
4
Xiyuan Hospital, China Academy of Chinese Medical Science, Beijing, People’s Republic of China
30 months as a result of the relentless progression. Of note, it has been documented that about 10–20% of familial ALS are caused by mutations in the Cu/Zn-superoxide dismutase 1 (SOD1) (Hardiman et al. 2017; Kiernan et al. 2011; Valdmanis et al. 2009; Rosen et al. 1993). SOD1 is an enzyme cata
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