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Investigation of the neuroprotective and neuritogenic effects of halotolerant Penicillium flavigenum-derived sorbicillin-like compounds on PC-12 Adh cells

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Abstract

Parkinson's disease (PD) is an adult-onset neurodegenerative condition caused by oxidative stress and mitochondrial malfunction. In this study, the neuroprotective and neuritogenic activity of water fraction (Sw-fr) containing sorbicillin-like active metabolites of halotolerant P. flavigenum isolated from Salt Lake in Konya, Turkey were investigated on a 6-hydroxydopamine (6-OHDA)-induced PD in vitro PC-12 Adh cell model. Firstly, Sw-fr containing sorbicillin-like active metabolites were extracted from P. flavigenum and was compared with a sorbicillin standard by liquid chromatography-mass spectrometry (LC–MS). Then, the effects of non-cytotoxic concentrations of Sw-fr on the 6-OHDA-induced PD cell model were investigated via real-time cell proliferation analysis using the RTCA DP instrument. The effects of these concentrations on mitochondrial membrane integrity, caspase-3 were investigated by flow cytometry. Neurite outgrowth analysis and immunofluorescence staining were used to explore the neuritogenic effects of neuroprotective doses. By improving PC-12 Adh cell viability, decreasing reactive oxygen species production, and reducing apoptotic cell death, 1 and 10 μg/mL Sw-fr and sorbicillin standard proved neuroprotective against 6-OHDA-induced neurotoxicity. Furthermore, 1 and 10 µg/mL Sw-fr significantly induced neurite outgrowth. As a result, sorbicillin-like active metabolites containing Sw-fr were found to have neuroprotective and neuritogenic effects. Sorbicillin-like metabolites obtained from fungi may be novel natural medicines for neurodegenerative diseases.

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All data generated or analysed during this study are included in this published article (and its supplementary information files).

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Acknowledgements

This research was supported by Scientific and Technological Research Council of Turkey (Project Number: 116R006).

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Authors and Affiliations

  1. Department of Pharmacology, Faculty of Pharmacy, Anadolu University, 26210, Eskisehir, Turkey

    Elif Kaya Tilki & Miriş Dikmen

  2. Tavas Vocational School of Health Services, Pamukkale University, Denizli, Turkey

    Selin Engür Öztürk

  3. Department of Pharmaceutical Microbiology, Faculty of Pharmacy, Anadolu University, 26210, Eskisehir, Turkey

    Mustafa Güçlü Özarda & Zerrin Cantürk

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  1. Elif Kaya Tilki
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  2. Selin Engür Öztürk
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  3. Mustafa Güçlü Özarda
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  4. Zerrin Cantürk
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  5. Miriş Dikmen
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Correspondence to Elif Kaya Tilki.

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Kaya Tilki, E., Engür Öztürk, S., Özarda, M.G. et al. Investigation of the neuroprotective and neuritogenic effects of halotolerant Penicillium flavigenum-derived sorbicillin-like compounds on PC-12 Adh cells. Cytotechnology 73, 801–813 (2021). https://doi.org/10.1007/s10616-021-00498-9

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