Abstract
The marine habitat provides a large number of structurally-diverse bioactive compounds for drug development. Marine sponges have been studied over many years and are found to be a rich source of these bioactive chemicals. This study is focused on the evaluation of the activity of six diterpene derivatives isolated from Spongionella sp. on mitochondrial function using an oxidative in vitro stress model. The test compounds include the Gracilins (A, H, K, J and L) and tetrahydroaplysulphurin-1. Compounds were co-incubated with hydrogen peroxide for 12 hours to determine their protective capacities and their effect on markers of apoptosis and Nrf2/ARE pathways was evaluated. Results conclude that Gracilins preserve neurons against oxidative damage, and that in particular, tetrahydroaplysulphurin-1 shows a complete neuroprotective activity. Oxidative stress is linked to mitochondrial dysfunction and consequently to neurodegenerative disorders like Parkinson and Alzheimer diseases, Friedreich ataxia or Amyotrophic lateral sclerosis. This neuroprotection against oxidation conditions suggest that these metabolites could be interesting lead candidates in drug development for neurodegenerative diseases.
Highlights
Sponges are the animals of the phylum Porifera
In order to study the influence of natural compounds over mitochondrial activity in an oxidative stress in vitro model, H2O2 was used as oxidizing agent
Since neurodegenerative diseases are closely associated with oxidative stress, these compounds are interesting candidates for drug development
Summary
Sponges are the animals of the phylum Porifera. They are multicellular invertebrates dating back. The apoptosis intrinsic pathways are directly related to mitochondria and they are activated by several stress conditions that lead to outer mitochondrial membrane permeabilization and the consequent release of cytochrome C (Cyt C) This protein is going to be trafficked to the apoptosome through its association with the apoptotic protease-activating factor (Apaf1) and deoxyadenosine triphosphate (dATP). Oxidative stress is associated with mitochondrial dysfunction and is a common feature in neurodegenerative diseases, while, on the other hand, natural products obtained from sponges have demonstrated antioxidant activity and neuroprotective abilities These two facts have led us to study the effect of these six natural diterpenes isolated from Spongionella sp. These two facts have led us to study the effect of these six natural diterpenes isolated from Spongionella sp. on mitochondrial function in cortical neurons under oxidative stress conditions, their capacity to regulate the antioxidant Nrf2/ARE pathway, inhibition of apoptosis and their possible future application to drug development for neurodegenerative disorders
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