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

Author:

Yurchenko Ekaterina A.ORCID,Kolesnikova Sophia A.,Lyakhova Ekaterina G.ORCID,Menchinskaya Ekaterina S.,Pislyagin Evgeny A.ORCID,Chingizova Ekaterina A.,Aminin Dmitry L.

Abstract

The results of an investigation of the protective effects of five lanostane triterpenoids: 3β-acetoxy-7β,8β-epoxy-5α-lanost-24-en-30,9α-olide (1), 3β-hydroxy-7β,8β-epoxy-5α-lanost-24-en- 30,9α-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.

Publisher

MDPI AG

Subject

Chemistry (miscellaneous),Analytical Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Molecular Medicine,Drug Discovery,Pharmaceutical Science

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1. Protection Activity of 1,4-Naphthoquinones in Rotenone-Induced Models of Neurotoxicity;Marine Drugs;2024-01-25

2. Linking Heat Shock Protein 70 and Parkin in Parkinson’s Disease;Molecular Neurobiology;2023-08-01

3. Neuroprotective compounds from marine invertebrates;Beni-Suef University Journal of Basic and Applied Sciences;2023-07-28

4. Advances in Cytoprotective Drug Discovery;Molecules;2023-06-02

5. Sea God- Sponges: Toxins and Secondary Metabolites;Iranian South Medical Journal;2021-10-01

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