| Summary: | The results of an investigation of the protective effects of five lanostane triterpenoids: 3<i>β</i>-acetoxy-7<i>β</i>,8<i>β</i>-epoxy-5<i>α</i>-lanost-24-en-30,9<i>α</i>-olide (<b>1</b>), 3<i>β</i>-hydroxy-7<i>β</i>,8<i>β</i>-epoxy-5<i>α</i>-lanost-24-en- 30,9<i>α</i>-olide (<b>2</b>), 29-<i>nor</i>-penasterone (<b>3</b>), penasterone (<b>4</b>), and acetylpenasterol (<b>5</b>), from a marine sponge, <i>Penares</i> 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 (<b>5</b>), 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 <b>1</b>–<b>5</b> and their chemical structure was also discussed.
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