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

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.

Sea Anemone Kunitz-Type Peptides Demonstrate Neuroprotective Activity in the 6-Hydroxydopamine Induced Neurotoxicity Model

“…Initially, cells were incubated in cultural flasks until sub-confluent (~80%). For testing, Neuro-2a cells were seeded in 96-well plates and experiments were started after 24 h [ 37 ].…”

Neuroprotective Effect of 1,4-Naphthoquinones in an In Vitro Model of Paraquat and 6-OHDA-Induced Neurotoxicity

“…The data were processed by MARS Data Analysis v. 3.01R2 (BMG Labtech, Ortenberg, Germany). The results were presented as a percentage of positive control data [ 32 ].…”

Immunomodulatory properties of characellide A on human peripheral blood mononuclear cells

“…Since some of the sponge-derived metabolites were included in clinical and preclinical trials showing their efficacy as modulators of immune response (Gunasekera et al 1989;Alcaraz and Paya 2006;Fattorusso and Taglialatela-Scafati 2009;Sagar et al 2010;Bibi et al 2017;Negi et al 2017;Karpinski 2019;Yurchenko et al 2020), the observation that characellide A is a potent in vitro activator of PBMC raising interesting perspectives on its potential pharmacological application.…”

“…of much research which has identified thousands of different natural products including 300 novel compounds with interesting pharmacological features (Faulkner 2000(Faulkner , 2001(Faulkner , 2002Sipkema et al 2005;Blunt et al 2006;Mehbub et al 2014). Interestingly, some of the sponge-derived metabolites have been included in clinical and preclinical trials showing their efficacy as anti-inflammatory (Alcaraz and Paya 2006), antitumoral (Negi et al 2017), immunosuppressive (Gunasekera et al 1989), neurosuppressive (Yurchenko et al 2020), antiviral (Sagar et al 2010), antimalarial (Fattorusso and Taglialatela-Scafati 2009), antibiotic (Bibi et al 2017) or antifungal (Karpinski 2019) compounds. Glycolipids represent the main components of several marine organisms and have been identified as potent activators of immune cells by binding to CD1d molecule (Wu et al 2008).…”