Research Institute of Orthopedics, the Jiangnan Hospital affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, China.
Research Institute of Orthopedics, the Jiangnan Hospital affiliated to Zhejiang Chinese Medical University, Hangzhou, Zhejiang, China; Hangzhou Xiaoshan Hospital of Traditional Chinese Medicine, Hangzhou, Zhejiang, China.
Ecotoxicol Environ Saf. 2024 Oct 15;285:117047. doi: 10.1016/j.ecoenv.2024.117047. Epub 2024 Sep 24.
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.
莫诺苷(MOR)在治疗莠去津(ATZ)诱导的皮肤损伤方面显示出巨大的潜力。本研究旨在阐明 MOR 减轻脂质代谢紊乱和抑制铁死亡以修复 ATZ 诱导的皮肤损伤的作用机制。将 20 只 C57BL/6 小鼠分为四组:对照组、ATZ 组、MOR-H 组和 MOR-L 组,每组 5 只。经过一个月的干预后,采集小鼠皮肤组织进行非靶向脂质组学分析。随后,对与铁死亡相关的指标进行评估。非靶向脂质组学分析显示,ATZ 与 Ctrl 组相比有 127 个差异代谢物。MOR-L 与 ATZ 组相比有 57 个差异代谢物。MOR-H 与 ATZ 组相比有 34 个差异代谢物。MOR-L 给药后脂质逆转最明显,主要涉及磷脂、神经酰胺和鞘磷脂。MOR-L 组中,与铁死亡相关的指标 GPX4、Ferritin、MDA、SOD 和 GSH-PX 以及与细胞凋亡相关的指标 p21 和 p53 的水平下降最明显(均 P<0.05)。MOR 可能通过逆转 ATZ 诱导的脂质代谢紊乱、抑制铁死亡和过度氧化应激的发生,延缓细胞衰老,纠正皮肤损伤。