Neuroprotection and NRF2 signaling cascade analysis of new synthetic cinnamic acid-Eugenol hybrids

Abstract

Oxidative stress can damage cells and cause age-related illnesses such as Alzheimer's, Parkinson's, and Huntington's. NRF2 is a protein that regulates the expression of genes involved in antioxidant defense, detoxification, and other cellular processes that protect against oxidative damage and cellular homeostasis. This study looked at newly synthesized Cinnamic Acid-Eugenol hybrid derivatives and their effect on SH-SY5Y neurons under oxidative stress through the NRF2 signaling pathway. Derivatives were synthesized and confirmed through FT-IR, NMR, and Mass spectroscopy. Derivatives of Cinnamic Acid-Eugenol hybrid were then tested on human SH-SY5Y cells under an oxidative stress model induced by hydrogen peroxide (H2O2). Effects; on cell viability, ROS levels, protein carbonyl content, and gene expression of NRF2 and phase II antioxidative enzymes measured after 24 h. Derivatives (A, B) were observed to enhance the viability of SH-SY5Y cells by defending against oxidative stress, reducing intracellular reactive oxygen species and carbonylated proteins, and increasing gene expression levels of NRF2 and associated genes such as; NQO-1 and GSTK1.These study highlights that these derivatives demonstrated a neuroprotective action on SH-SY5Y cells through various neuroprotective mechanisms.