Brusatol

This study investigated the potential of Porphyra derivatives (PD), including Porphyra334, to activate the nuclear factor erythroid 2-related factor 2 (NRF2) pathway in porcine oocytes to enhance oocyte competency and intracellular networks. Conventional methods for manipulating mitochondrial and antioxidant pathways often rely upon genetic modifications that are impractical for direct application in humans. We hypothesized that PD serves as a natural regulator of the NRF2 pathway without requiring genetic intervention. To test this hypothesis, brusatol (Bru), a direct NRF2 inhibitor, was used to evaluate the specific role of PD in NRF2-mediated processes. The results demonstrated that PD significantly improved oocyte maturation, blastocyst formation, and mitochondrial function, including subsequent lipid metabolism. PD activates NRF2 and its downstream antioxidant response elements (AREs), whereas Bru inhibits these effects. Co-treatment with PD and Bru resulted in the partial recovery of NRF2 activity. These findings suggest that PD functions as a toggle for NRF2 activation, potentially offering a non-genetic strategy for enhancing oocyte quality and embryo development by modulating antioxidant mechanisms and mitochondrial functions. This study provides new avenues for investigating natural compounds in the context of reproductive biology and assisted reproduction technologies (ARTs).

JOURNAL/nrgr/04.03/01300535-202412000-00030/figure1/v/2024-05-29T122840Z/r/image-tiffMemory loss and dementia are major public health concerns with a substantial economic burden. Oxidative stress has been shown to play a crucial role in the pathophysiology of hippocampal damage-induced memory impairment. To investigate whether the antioxidant and anti-inflammatory compound vanillylacetone (zingerone) can protect against hippocampal damage and memory loss induced by cadmium chloride (CdCl2) administration in rats, we explored the potential involvement of the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway, which is known to modulate oxidative stress and inflammation. Sixty healthy male Wistar rats were divided into five groups: vehicle-treated (control), vanillylacetone, CdCl2, vanillylacetone + CdCl2, vanillylacetone + CdCl2+ brusatol (a selective pharmacological Nrf2 inhibitor) groups. Vanillylacetone effectively attenuated CdCl2-induced damage in the dental gyrus of the hippocampus and improved the memory function assessed by the Morris Water Maze test. Additionally, vanillylacetone markedly decreased the hippocampal tissue levels of inflammatory biomarkers (interleukin-6, tumor necrosis factor-α, intracellular cell adhesive molecules) and apoptosis biomarkers (Bax and cleaved caspase-3). The control and CdCl2-treated groups treated with vanillylacetone showed reduced generation of reactive oxygen species, decreased malondialdehyde levels, and increased superoxide dismutase and glutathione activities, along with significant elevation of nuclear Nrf2 mRNA and protein expression in hippocampal tissue. All the protective effects of vanillylacetone were substantially blocked by the co-administration of brusatol (a selective Nrf2 inhibitor). Vanillylacetone mitigated hippocampal damage and memory loss induced by CdCl2, at least in part, by activating the nuclear transcription factor Nrf2. Additionally, vanillylacetone exerted its potent antioxidant and anti-inflammatory actions.