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

• Published in: Cytotechnology (Dordrecht) Vol. 73; no. 6; pp. 801 - 813
• Main Authors: Kaya Tilki, Elif, Engür Öztürk, Selin, Özarda, Mustafa Güçlü, Cantürk, Zerrin, Dikmen, Miriş
• Format: Journal Article
• Language: English
• Published: Dordrecht Springer Netherlands 01.12.2021; Springer Nature B.V
• Subjects: 6-Hydroxydopamine; Acids; Antioxidants; Apoptosis; Axonogenesis; Biochemistry; Biomedicine; Biotechnology; Brain; Cancer; Caspase-3; Cell death; Cell proliferation; Cell viability; Cells; Chemistry; Chemistry and Materials Science; Chromatography; Cytotoxicity; Flow cytometry; Free radicals; Fungi; Immunofluorescence; Investigations; Lakes; Liquid chromatography; Mass spectroscopy; Metabolites; Mitochondria; Molecular weight; Movement disorders; Nervous system; Neurodegenerative diseases; Neuroprotection; Neurotoxicity; Original; Original Article; Oxidative stress; Parkinson's disease; Pathogenesis; Penicillin; Reactive oxygen species; Salinity tolerance; Signal transduction; Germany; Neuroprotection; Neuritogenic; Sorbicillin; Parkinson’s disease; Penicillium flavigenum
• ISSN: 0920-9069; 1573-0778
• DOI: 10.1007/s10616-021-00498-9

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.