Cuminaldehyde as the Major Component of Cuminum cyminum, a Natural Aldehyde with Inhibitory Effect on Alpha-Synuclein Fibrillation and Cytotoxicity.
Fibrillation of alpha-synuclein (α-SN) is a critical process in the pathophysiology of several neurodegenerative diseases, especially Parkinson's disease. Application of bioactive inhibitory compounds from herbal extracts is a potential therapeutic approach for this cytotoxic process. Here, we investigated the inhibitory effects of the Iranian Cuminum cyminum essential oil on the fibrillation of α-SN. Analysis of different fractions from the total extract identified cuminaldehyde as the active compound involved in the antifibrillation activity. In comparison with baicalein, a well-known inhibitor of α-SN fibrillation, cuminaldehyde showed the same activity in some aspects and a different activity on other parameters influencing α-SN fibrillation. The presence of spermidine, an α-SN fibrillation inducer, dominantly enforced the inhibitory effects of cuminaldehyde even more intensively than baicalein. Furthermore, the results from experiments using preformed fibrils and monobromobimane-labeled monomeric protein also suggest that cuminaldehyde prevents α-SN fibrillation even in the presence of seeds, having no disaggregating impact on the preformed fibrils. Structural studies showed that cuminaldehyde stalls protein assembly into β-structural fibrils, which might be achieved by the interaction with amine groups through its aldehyde group as a Schiff base reaction. This assumption was supported by FITC labeling efficiency assay. In addition, cytotoxicity assays on PC12 cells showed that cuminaldehyde is a nontoxic compound, treatment with cuminaldehyde throughout α-SN fibrillation showed no toxic effects on the cells. Taken together, these results show for the first time that the small abundant natural compound, cuminaldehyde, can modulate α-SN fibrillation. Hence, suggesting that such natural active aldehyde could have potential therapeutic applications.
Dept. of Industrial and Environmental Biotechnology, National Inst. of Genetic Engineering and Biotechnology, Tehran, Iran.
Dina
D
Morshedi
Dept. of Industrial and Environmental Biotechnology, National Inst. of Genetic Engineering and Biotechnology, Tehran, Iran.
Farhang
F
Aliakbari
Dept. of Industrial and Environmental Biotechnology, National Inst. of Genetic Engineering and Biotechnology, Tehran, Iran.
Amir
A
Tayaranian-Marvian
Bioinformatics and High Performance Computing Research Group, Univ. Católica San Antonio de Murcia (UCAM), Spain.
Afshin
A
Fassihi
Neurologische Klinik und Poliklinik., Klinikum der Univ. München, Munich, Germany.|Munich Cluster for Systems Neurology, SyNergy Clinician Scientist Group, Germany.
Francisco
F
Pan-Montojo
Bioinformatics and High Performance Computing Research Group, Univ. Católica San Antonio de Murcia (UCAM), Spain.
Horacio
H
Pérez-Sánchez
D000818:Animals; D001547:Benzaldehydes / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D028527:Cuminum / Q000737:chemistry*; D000081007:Cymenes; D044950:Flavanones / Q000494:pharmacology; D009822:Oils, Volatile / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D016716:PC12 Cells; D010300:Parkinson Disease / Q000503:physiopathology; D010936:Plant Extracts / Q000009:adverse effects / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation / Q000187:drug effects; D051381:Rats; D012639:Seeds / Q000737:chemistry; D051844:alpha-Synuclein / Q000378:metabolism*
D001547:Benzaldehydes; D000081007:Cymenes; D044950:Flavanones; D009822:Oils, Volatile; D010936:Plant Extracts; D051844:alpha-Synuclein; C006680:baicalein; C007165:cuminaldehyde
Cuminum cyminum; alpha-synuclein; antifibrillation; baicalein; cuminaldehyde; essential oil