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      Metabolic Fingerprinting of Different Sideritis Taxa Infusions and Their Neurogenic Activity

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          Abstract

          Over the last years, Sideritis extracts were shown to improve memory. However, their potential to promote the generation of new neurons, starting with the neuronal differentiation of neural stem cells, remains unexplored. Therefore, the present study aimed to evaluate the neurogenic effects of different Sideritis infusions in neural stem and precursor cells and their impact on cell viability. Moreover, the metabolic fingerprints were recorded using LC-DAD, LC-HRESIMS, and GC-MS. The neurogenic potential of infusions of the eight Sideritis taxa tested was as potent as the classical neuronal inducer combination of retinoic acid and valproic acid. Further cytotoxicity assays revealed that the IC50 values of the extracts were between 163 and 322 µg/mL. Hierarchical cluster analyses of the metabolic fingerprints unveiled that the two Sideritis taxa with the lowest IC50 values were the most divergent in the analytical techniques used. As the analysis focused on polyphenols, it is reasonable to assume that these compounds are responsible for the effect on the cell viability of SH-SY5Y neuroblastoma cells. This study is the first report on the neurogenic potential of Sideritis taxa and might support the use of Sideritis herbal preparations in the context of neurodegenerative diseases.

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          The SH-SY5Y cell line in Parkinson’s disease research: a systematic review

          Parkinson’s disease (PD) is a devastating and highly prevalent neurodegenerative disease for which only symptomatic treatment is available. In order to develop a truly effective disease-modifying therapy, improvement of our current understanding of the molecular and cellular mechanisms underlying PD pathogenesis and progression is crucial. For this purpose, standardization of research protocols and disease models is necessary. As human dopaminergic neurons, the cells mainly affected in PD, are difficult to obtain and maintain as primary cells, current PD research is mostly performed with permanently established neuronal cell models, in particular the neuroblastoma SH-SY5Y lineage. This cell line is frequently chosen because of its human origin, catecholaminergic (though not strictly dopaminergic) neuronal properties, and ease of maintenance. However, there is no consensus on many fundamental aspects that are associated with its use, such as the effects of culture media composition and of variations in differentiation protocols. Here we present the outcome of a systematic review of scientific articles that have used SH-SY5Y cells to explore PD. We describe the cell source, culture conditions, differentiation protocols, methods/approaches used to mimic PD and the preclinical validation of the SH-SY5Y findings by employing alternative cellular and animal models. Thus, this overview may help to standardize the use of the SH-SY5Y cell line in PD research and serve as a future user’s guide. Electronic supplementary material The online version of this article (doi:10.1186/s13024-017-0149-0) contains supplementary material, which is available to authorized users.
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            Considerations for the use of SH-SY5Y neuroblastoma cells in neurobiology.

            The use of primary mammalian neurons derived from embryonic central nervous system tissue is limited by the fact that once terminally differentiated into mature neurons, the cells can no longer be propagated. Transformed neuronal-like cell lines can be used in vitro to overcome this limitation. However, several caveats exist when utilizing cells derived from malignant tumors. In this context, the popular SH-SY5Y neuroblastoma cell line and its use in in vitro systems is described. Originally derived from a metastatic bone tumor biopsy, SH-SY5Y (ATCC(®) CRL-2266™) cells are a subline of the parental line SK-N-SH (ATCC(®) HTB-11™). SK-N-SH were subcloned three times; first to SH-SY, then to SH-SY5, and finally to SH-SY5Y. SH-SY5Y were deposited to the ATCC(®) in 1970 by June L. Biedler.Three important characteristics of SH-SY5Y cells should be considered when using these cells in in vitro studies. First, cultures include both adherent and floating cells, both types of which are viable. Few studies address the biological significance of the adherent versus floating phenotypes, but most reported studies utilize adherent populations and discard the floating cells during media changes. Second, early studies by Biedler's group indicated that the parental differentiated SK-N-SH cells contained two morphologically distinct phenotypes: neuroblast-like cells and epithelial-like cells (Ross et al., J Nat Cancer Inst 71:741-747, 1983). These two phenotypes may correspond to the "N" and "S" types described in later studies in SH-SY5Y by Encinas et al. (J Neurochem 75:991-1003, 2000). Cells with neuroblast-like morphology are positive for tyrosine hydroxylase (TH) and dopamine-β-hydroxylase characteristic of catecholaminergic neurons, whereas the epithelial-like counterpart cells lacked these enzymatic activities (Ross et al., J Nat Cancer Inst 71:741-747, 1983). Third, SH-SY5Y cells can be differentiated to a more mature neuron-like phenotype that is characterized by neuronal markers. There are several methods to differentiate SH-SY5Y cells and are mentioned below. Retinoic acid is the most commonly used means for differentiation and will be addressed in detail.
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              A network dysfunction perspective on neurodegenerative diseases.

              Patients with Alzheimer's disease or other neurodegenerative disorders show remarkable fluctuations in neurological functions, even during the same day. These fluctuations cannot be caused by sudden loss or gain of nerve cells. Instead, it is likely that they reflect variations in the activity of neural networks and, perhaps, chronic intoxication by abnormal proteins that the brain is temporarily able to overcome. These ideas have far-reaching therapeutic implications.

                Author and article information

                Contributors
                (View ORCID Profile)
                (View ORCID Profile)
                Journal
                Planta Medica
                Planta Med
                Georg Thieme Verlag KG
                0032-0943
                1439-0221
                September 01 2023
                September 2023
                April 12 2023
                May 23 2023
                September 2023
                : 89
                : 11
                : 1087-1096
                Affiliations
                [1 ]Section of Pharmacognosy & Chemistry of Natural Products, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Panepistimiopolis, Zografou, Athens, Greece
                [2 ]Weihenstephan-Triesdorf University of Applied Sciences, Organic-Analytical Chemistry, Straubing, Germany
                [3 ]Institute of Experimental Neuroregeneration, Spinal Cord Injury and Tissue Regeneration Center Salzburg (SCI-TReCS), Paracelsus Medical University Salzburg, Salzburg, Austria
                [4 ]Austrian Cluster for Tissue Regeneration, Vienna, Austria
                [5 ]TUM Campus Straubing for Biotechnology and Sustainability, Technical University of Munich, Straubing, Germany
                Article
                10.1055/a-2072-2351
                bb979290-07d3-424b-a434-3a363b614bd9
                © 2023
                History

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