Lanostane Triterpenoid Metabolites from a Penares sp. Marine Sponge Protect Neuro-2a Cells against Paraquat Neurotoxicity.

Autor: Yurchenko EA; Laboratory of Bioassays and Mechanism of Action of Biologically Active Substances, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, prosp. 100 let Vladivostoku 159, 690022 Vladivostok, Russia., Kolesnikova SA; Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, prosp. 100 let Vladivostoku 159, 690022 Vladivostok, Russia., Lyakhova EG; Laboratory of Marine Natural Products Chemistry, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, prosp. 100 let Vladivostoku 159, 690022 Vladivostok, Russia., Menchinskaya ES; Laboratory of Bioassays and Mechanism of Action of Biologically Active Substances, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, prosp. 100 let Vladivostoku 159, 690022 Vladivostok, Russia., Pislyagin EA; Laboratory of Bioassays and Mechanism of Action of Biologically Active Substances, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, prosp. 100 let Vladivostoku 159, 690022 Vladivostok, Russia., Chingizova EA; Laboratory of Bioassays and Mechanism of Action of Biologically Active Substances, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, prosp. 100 let Vladivostoku 159, 690022 Vladivostok, Russia., Aminin DL; Laboratory of Bioassays and Mechanism of Action of Biologically Active Substances, G.B. Elyakov Pacific Institute of Bioorganic Chemistry, prosp. 100 let Vladivostoku 159, 690022 Vladivostok, Russia.; Department of Biomedical Science and Environmental Biology, Kaohsiung Medical University, No. 100, Shin-Chuan 1st Road, Sanmin Dist., Kaohsiung City 80708, Taiwan.
Jazyk: angličtina
Zdroj: Molecules (Basel, Switzerland) [Molecules] 2020 Nov 18; Vol. 25 (22). Date of Electronic Publication: 2020 Nov 18.
DOI: 10.3390/molecules25225397
Abstrakt: The results of an investigation of the protective effects of five lanostane triterpenoids: 3 β -acetoxy-7 β ,8 β -epoxy-5 α -lanost-24-en-30,9 α -olide ( 1 ), 3 β -hydroxy-7 β ,8 β -epoxy-5 α -lanost-24-en- 30,9 α -olide ( 2 ), 29- nor -penasterone ( 3 ), penasterone ( 4 ), and acetylpenasterol ( 5 ), from a marine sponge, Penares sp., against paraquat-induced neuroblastoma Neuro-2a cell damage, are described. The influence of all compounds on viability of the Neuro-2a cells treated with paraquat (PQ) was studied with MTT and fluorescein diacetate assays as well as propidium iodide straining. 1,1-Diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity of the compounds as well as their influence on reactive oxygen species (ROS) level and mitochondrial membrane potential in PQ-treated neuronal cells were analyzed. Finally, the effect of the compounds on intracellular level of heat shock protein 70 kDa (Hsp70) and neurite outgrowth in PQ-treated Neuro-2a cells were studied. Studied triterpenoids demonstrated protective effects against PQ-induced neurotoxicity associated with the ability to reduce ROS intracellular level and diminish mitochondrial dysfunction. Acetylpenasterol ( 5 ), as a more promising neuroprotective compound, significantly increased the viability of Neuro-2a cells incubated with PQ as well as decreased intracellular ROS level in these cells. Moreover, acetylpenasterol induced Hsp70 expression in PQ-treated cells. It was also shown to inhibit PQ-induced neurite loss and recovered the number of neurite-bearing cells. The relationship between neuroprotective activity of the investigated compounds 1 - 5 and their chemical structure was also discussed.
Databáze: MEDLINE
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