A study on the modulation of alpha-synuclein fibrillation by Scutellaria pinnatifida extracts and its neuroprotective properties

• Published in: PLOS ONE Vol. 12; no. 9; p. e0184483
• Main Authors: Sashourpour, Mahdyeh, Zahri, Saber, Radjabian, Tayebeh, Ruf, Viktoria, Pan-Montojo, Francisco, Morshedi, Dina
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science (PLoS) 28.09.2017; Public Library of Science
• Subjects: Agglomeration; alpha-Synuclein; alpha-Synuclein - chemistry; alpha-Synuclein - toxicity; Animals; Antioxidants; Apoptosis; Biology; Biology and Life Sciences; Biotechnology; Butanol; Care and treatment; Cell Death; Cell Death - drug effects; Degeneration; Dichloromethane; Disease; Dopamine; Dopamine receptors; Dopaminergic Neurons; Dopaminergic Neurons - drug effects; Dopaminergic Neurons - metabolism; Fibrillation; Flavonoids; Flavonoids - metabolism; Free Radical Scavengers; Free Radical Scavengers - pharmacology; Genetic aspects; Genetic engineering; Herbal medicine; High-performance liquid chromatography; Humans; Inhibition; Liquid chromatography; Mass spectroscopy; Medicinal plants; Medicine; Medicine and Health Sciences; Microscopy, Fluorescence; Movement disorders; Neurodegeneration; Neurodegenerative diseases; Neurons; Neuroprotection; Neuroprotective Agents; Neuroprotective Agents - pharmacology; Neurotoxicity; Oligomers; Oxidative stress; Paraquat; Paraquat - toxicity; Parkinson disease; Parkinson's disease; Pathogenesis; PC12 Cells; Pharmaceuticals; Pheochromocytoma cells; Physical Sciences; Physiological aspects; Plant Extracts; Plant Extracts - pharmacology; Plant Roots; Plant Roots - chemistry; Polyphenols; Properties (attributes); Protein Multimerization; Protein Multimerization - drug effects; Q; R; Rats; Research and Analysis Methods; Research Article; Scavenging; Science; Scutellaria; Scutellaria - chemistry; Spectroscopy; Synuclein; Toxicity; Iran; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0184483

Aggregation of alpha-synuclein (α-SN) is a key pathogenic event in Parkinson's disease (PD) leading to dopaminergic degeneration. The identification of natural compounds inhibiting α-SN aggregation may have a major role in treating PD. Different Scutellaria species are known as valuable medicinal plants, primarily due to their high flavonoid levels. Scutellaria pinnatifida (S. pinnatifida) is endemic to Iran; however, the knowledge of its pharmaceutical properties is limited. Here we report that S. pinnatifida extracts have an anti-fibrillation effect on α-SN aggregation and neuroprotective properties on PC12 and primary dopaminergic neurons. Treatment during α-SN fibril formation with S. pinnatifida extracts showed that the extractions performed with dichloromethane (DCMEx) and n-butanol (BuOHEx) strongly inhibited α-SN fibrillation. TLC-based analysis revealed that S. pinnatifida contains a great amount of flavonoids with high antioxidant properties as shown using a radical scavenging assay. Further analysis using HPLC and Mass spectroscopy on the DCMEx revealed the presence of baicalein in this extract. We then selected the more efficient extracts based on cell viability and ROS scavenging on PC12 cells and tested their neuroprotective properties on primary dopaminergic neurons. Our results showed the extracts strongly protected against α-SN oligomers. Surprisingly, they also neutralized the severe toxicity of paraquat. Therefore, S. pinnatifida may be a potential valuable medicinal herb for further studies related to the treatment of PD.