Antioxidant potentials of furanodihydrobenzoxanthones from Artocarpus elasticus and their protection against oxLDL induced injury in SH-SY5Y cells

Abstract

Exposure to reactive oxygen species (ROS) leads to the oxidation of low-density lipoproteins (LDL), converting them into oxidized ones (oxLDL), which are involved in the pathogenesis of Alzheimer's disease, suggesting a potential link between lipid dysregulation and neurodegenerative processes. Phenolic metabolites derived from Artocarpus elasticus root bark were found to possess significant antioxidant properties at three different radical scavenging assays, including 2,2-diphenyl-1-picrylhydrazyl (DPPH), oxygen radical absorbance capacity (ORAC), and thiobarbituric acid reactive substances (TBARS). Among them, furanodihydrobenzoxanthones (1-3) demonstrated notable protection against Cu²⁺ induced LDL oxidation, with IC₅₀ values ranging from 0.9 to 2.9 μM in measurement of the malondialdehyde (MDA) production at TBARS and prolonged lag times (>180 min) in the generation of conjugated diene (CD). At a concentration of 10 μM, all three compounds (1-3) effectively protected against LDL oxidation as determined by relative electrophoretic mobility (REM). The most potent compound 1 defended human neuroblastoma SH-SY5Y cells from oxLDL-mediated dysfunction, including oxLDL-induced cytotoxicity, inhibited reactive oxygen species (ROS) formation, and enhancing mitochondrial membrane potential (ΔΨm). Individual components annotation in the ethylacetate extract was performed using LC-ESI-QTOF/MS, which serves as a chemotaxonomic marker for A. elasticus root barks.

Keywords: Antioxidant; Artocarpus elasticus; Furanodihydrobenzoxanthone; Human neuroblastoma SH-SY5Y cells; LDL oxidation.