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6
Vestnik FEB RAS. 2018. № 6 Supplement
UDC 547.99+615.275.4 DOI: 10.25808/08697698.2018.202.6S.066
E.A. YURCHENKO, E.S. MENCHINSKAYA, E.A. PISLYAGIN, A.N. YURCHENKO
Neuroprotection activity of marine fungi metabolites in toxin-induced model of Parkinson's disease
Key words: marine fungi metabolites, neuroprotection, Parkinson's disease
Currently, Parkinson's disease is the most common neurodegenerative disease after Alzheimer's disease and no less socially significant disease, regardless of countries and regions, and requires an intensive search for new drugs that can prevent or contain the development of Parkinson's disease. Some metabolites of marine fungi show a neuroprotective effect in the in vitro models of Parkinson's disease. Thus, neoequinulin A, a known metabolite of a number of fungi of the genera Aspergillus and Eurotium, reduced the neurotoxicity of rotenone and 1-methyl-4-phenylpyridinium for PC12 cells [1].
The aim of our work was investigation of a number of metabolites isolated from the marine fungi Aspergillus candidus KMM 4676, Eurotium niveoglaucum, Aspergillus flocculosus and Penicillium sp. KMM 4672 in 6-hydroxidopamine-induced model of Parkinson's disease. Totally, the neuroprotective activity of 41 marine fungi metabolites was studied. Neuroblastoma Neu-ro2a line cells (1*103 cells/well) were treated with 50 ^M of 6-hydroxydopamine (6-OHDA) during 1 h, after that neuroblastoma cells were cultivated with each investigated compound (10 ^M) during 24 h. In other experiments, the substances were added to the cells 1 h before the addition of the neurotoxin. Viability of cells was measured by MTT assay.
Isochromene 1 [3] statistically significant increased the neuroblastoma cell viability on 11% (1h before 6-OHDA adding) and 14% (1h after 6-OHDA adding) compared with 6-OHDA-treated cells. Mactanamide 2 [2] increased the neuroblastoma cell viability on 18% compared with 6-OHDA-treated cells regardless of the time of substance addition. When the concentration of 2 was reduced tenfold this neuroprotective effect was preserved. Candidusine A 3 had no effect on viability of 6-OHDA-treated cells but its 4"-dehydroxylated analoque 4 [4] increased cell viability on more than 30% (1h before 6-OHDA adding) and 29% (1h after 6-OHDA adding).
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* YURCHENKO Ekaterina Aleksandrovna - PhD, Researcher, MENCHINSKAYA Ekaterina Sergeevna- PhD, Researcher, PISLYAGIN Evgeny Alexandrovich - PhD, Researcher, YURCHENKO Anton Nikolaevitch - PhD, Researcher (G.B. Elyakov Pacific Institute of Bioorganic Chemistry, FEB RAS, Vladivostok, Russia).
*E-mail: dminae@mail.ru
The work was supported by RFBR grant № 18-34-00737
Thus, same marine fungal metabolites protect neuronal cells from damaging effect of 6-hydroxydopamine.
REFERENCES:
1. Akashi S., Kimura T., Takeuchi T., et al. Neoechinulin A impedes the progression of rotenone-induced cytotoxicity in PC12 cells // Biol. Pharm. Bull. 2011. Vol. 34, №2.P. 243-248.
2. Lorenz P., Jensen P.R., Fenical W. Mactanamide, a new fungistatic diketopiperazine produced by a marine Aspergillus sp // Nat. Prod. Lett. 1998. Vol.12, № 1.P. 55-60.
3. Smetanina O.F., Yurchenko A.N., Ivanets E.V., et al. Metabolites of the marine fungus Penicillium citrinum associated with a brown alga Padina sp. // Chem. Nat. Comp. 2016. Vol. 52, № 1. P. 111-112.
4. Yurchenko A.N., Ivanets E.V., Smetanina O.F.,et al. Metabolites of the marine fungus Aspergillus Candidus KMM 4676 associated with a kuril colonial ascidian // Chem. Nat. Comp. 2017. Vol. 53, № 4.P. 747-749.
