Psammaplin A and Its Analogs Attenuate Oxidative Stress in Neuronal Cells Through Peroxisome Proliferator-Activated Receptor γ Activation

Overview

Journal J Nat Prod

Date 2024 Apr 18

PMID 38632902

Authors

Rebeca Alvarino

Amparo Alfonso

Jioji N Tabudravu

Jesus Gonzalez-Jartin

Khalid S Al Maqbali

Marwa Elhariry

Mercedes R Vieytes

Luis M Botana

Affiliations

Soon will be listed here.

Abstract

Psammaplins are sulfur containing bromotyrosine alkaloids that have shown antitumor activity through the inhibition of class I histone deacetylases (HDACs). The cytotoxic properties of psammaplin A (), the parent compound, are related to peroxisome proliferator-activated receptor γ (PPARγ) activation, but the mechanism of action of its analogs psammaplin K () and bisaprasin () has not been elucidated. In this study, the protective effects against oxidative stress of compounds -, isolated from the sponge , were evaluated in SH-SY5Y cells. The compounds improved cell survival, recovered glutathione (GSH) content, and reduced reactive oxygen species (ROS) release at nanomolar concentrations. Psammaplins restored mitochondrial membrane potential by blocking mitochondrial permeability transition pore opening and reducing cyclophilin D expression. This effect was mediated by the capacity of - to activate PPARγ, enhancing gene expression of the antioxidant enzymes catalase, nuclear factor E2-related factor 2 (Nrf2), and glutathione peroxidase. Finally, HDAC3 activity was reduced by - under oxidative stress conditions. This work is the first description of the neuroprotective activity of at low concentrations and the mechanism of action of and . Moreover, it links for the first time the previously described effects of in HDAC3 and PPARγ signaling, opening a new research field for the therapeutic potential of this compound family.

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