Morroniside repairs atrazine-induced skin damage by ameliorating lipid metabolism disorders and inhibiting ferroptosis

Morroniside (MOR) has shown great potential in treating atrazine (ATZ)-induced skin damage. This study aims to elucidate MOR's mechanism of action in mitigating lipid metabolism disorders and inhibiting ferroptosis to repair ATZ-induced skin damage. Twenty C57BL/6 mice were divided into four groups: the control group, the ATZ group, the MOR-H group and the MOR-L group, each comprising five mice. Following a one-month intervention, mouse skin tissues were harvested for untargeted lipid metabolomics analysis. Subsequently, the samples were assessed for indices related to ferroptosis. Untargeted lipid metabolomics analysis showed 127 differential metabolites in the ATZ vs. Ctrl group. There were 57 differential metabolites in the MOR-L vs. ATZ group. 34 differential metabolites in the MOR-H vs. ATZ group. the most obvious lipid reversal occurred after MOR-L administration, which primarily involved phospholipids, ceramides, and sphingomyelins. The levels of GPX4, Ferritin, MDA, SOD and GSH-PX, ferroptosis-related indicators, and the levels of p21 and p53, apoptosis-related indicators, were most significantly regressed in the MOR-L group (all P < 0.05). MOR may delay cellular aging and correct skin damage by reversing ATZ-induced lipid metabolism disorders, inhibiting ferroptosis and excessive oxidative stress occurrence. [Display omitted] •Atrazine exposure resulted in impairment of the skin barrier and metabolic disorders.•Atrazine induces oxidative stress, apoptosis, and ferroptosis in the skin.•Morroniside rescues atrazin-induced skin injury by stabilizing metabolism and correcting cell death.•This study offers insights into Atrazine-induced skin toxicity and the potential application of Morroniside.