Monoterpenoid Epoxidiol Ameliorates the Pathological Phenotypes of the Rotenone-Induced Parkinson’s Disease Model by Alleviating Mitochondrial Dysfunction

Monoterpenoid Epoxidiol Ameliorates the Pathological Phenotypes of the Rotenone-Induced Parkinson’s Disease Model by Alleviating Mitochondrial Dysfunction Full article

Journal

International Journal of Molecular Sciences
ISSN: 1661-6596

Output data

Year: 2023, Volume: 24, Number: 6, Pages: 5842 Pages count : 1 DOI: 10.3390/ijms24065842

Tags

epoxidiol; Parkinson’s disease; neurodegenerative diseases; rotenone; ROS; mitochondrial dysfunction; disease-modifying therapy

Authors

Aleksandrova Yulia ¹ , Chaprov Kirill ¹ , Podturkina Alexandra ² , Ardashov Oleg ² , Yandulova Ekaterina ¹ , Volcho Konstantin ² , Salakhutdinov Nariman ² , Neganova Margarita ¹

Affiliations

1	Institute of Physiologically Active Compounds at Federal Research Center of Problems of Chemical Physics and Medicinal Chemistry, Russian Academy of Sciences, Severnij Pr. 1, Chernogolovka 142432, Russia
2	Department of Medicinal Chemistry, N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry, Siberian Branch, Russian Academy of Sciences, Lavrentiev Ave., 9, Novosibirsk 630090, Russia

Parkinson’s disease is the second most common neurodegenerative disease. Unfortunately, there is still no definitive disease-modifying therapy. In our work, the antiparkinsonian potential of trans-epoxide (1S,2S,3R,4S,6R)-1-methyl-4-(prop-1-en-2-yl)-7-oxabicyclo [4.1.0]heptan-2,3-diol (E-diol) was analyzed in a rotenone-induced neurotoxicity model using in vitro, in vivo and ex vivo approaches. It was conducted as part of the study of the mitoprotective properties of the compound. E-diol has been shown to have cytoprotective properties in the SH-SY5Y cell line exposed to rotenone, which is associated with its ability to prevent the loss of mitochondrial membrane potential and restore the oxygen consumption rate after inhibition of the complex I function. Under the conditions of rotenone modeling of Parkinson’s disease in vivo, treatment with E-diol led to the leveling of both motor and non-motor disorders. The post-mortem analysis of brain samples from these animals demonstrated the ability of E-diol to prevent the loss of dopaminergic neurons. Moreover, that substance restored functioning of the mitochondrial respiratory chain complexes and significantly reduced the production of reactive oxygen species, preventing oxidative damage. Thus, E-diol can be considered as a new potential agent for the treatment of Parkinson’s disease.

Aleksandrova Y. , Chaprov K. , Podturkina A. , Ardashov O. , Yandulova E. , Volcho K. , Salakhutdinov N. , Neganova M.
Monoterpenoid Epoxidiol Ameliorates the Pathological Phenotypes of the Rotenone-Induced Parkinson’s Disease Model by Alleviating Mitochondrial Dysfunction
International Journal of Molecular Sciences. 2023. V.24. N6. P.5842. DOI: 10.3390/ijms24065842 WOS РИНЦ

Submitted:	Feb 13, 2023
Accepted:	Mar 17, 2023
Published online:	Mar 19, 2023

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