Department of Food and Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand.
The Halal Science Center, Chulalongkorn University, Bangkok, Thailand.
Sci Rep. 2023 Nov 21;13(1):20385. doi: 10.1038/s41598-023-47558-y.
Oxyresveratrol has been documented benefits for neurodegenerative disease. However, the specific molecular mechanisms and pathways involved is currently limited. This study aimed to investigate the potential neuroprotective mechanisms of oxyresveratrol using rotenone-induced human neuroblastoma SH-SY5Y cytotoxicity. Cells were divided into the following groups: control, rotenone, and oxyresveratrol pre-treated before being exposed to rotenone. Cellular assays were performed to investigate neuroprotective effects of oxyresveratrol. The results showed that 20 μM oxyresveratrol was effective in preventing rotenone-induced cell death and decreasing ROS levels in the cells. The alteration of metabolites and pathways involved in the neuroprotective activities of oxyresveratrol were further investigated using LC-QTOF-MS/MS untargeted metabolomics approach. We hypothesized that oxyresveratrol's neuroprotective effects would be associated with neurodegenerative pathways. A total of 294 metabolites were identified. 7,8-dihydrobiopterin exhibited the highest VIP scores (VIP > 3.0; p < 0.05), thus considered a biomarker in this study. Our results demonstrated that pretreatment with oxyresveratrol upregulated the level of 7,8-dihydrobiopterin compared to the positive control. Pathway analysis verified that 7,8-dihydrobiopterin was primarily associated with phenylalanine, tyrosine, and tryptophan metabolism (impact = 1, p < 0.001), serving as essential cofactors for enzymatic function in the dopamine biosynthesis pathway. In conclusion, oxyresveratrol may be benefit for the prevention of neurodegenerative diseases by increasing 7,8-dihydrobiopterin concentration.
氧代白藜芦醇已被证明对神经退行性疾病有益。然而，目前涉及的具体分子机制和途径有限。本研究旨在使用鱼藤酮诱导的人神经母细胞瘤 SH-SY5Y 细胞毒性来研究氧代白藜芦醇的潜在神经保护机制。细胞分为以下几组：对照组、鱼藤酮组和氧代白藜芦醇预处理组，然后暴露于鱼藤酮中。进行细胞测定以研究氧代白藜芦醇的神经保护作用。结果表明，20 μM 氧代白藜芦醇可有效预防鱼藤酮诱导的细胞死亡并降低细胞内 ROS 水平。使用 LC-QTOF-MS/MS 无靶向代谢组学方法进一步研究了氧代白藜芦醇参与神经保护活性的代谢物和途径的变化。我们假设氧代白藜芦醇的神经保护作用与神经退行性途径有关。共鉴定出 294 种代谢物。7,8-二氢生物蝶呤表现出最高的 VIP 评分（VIP>3.0；p<0.05），因此被认为是本研究中的生物标志物。我们的结果表明，与阳性对照组相比，氧代白藜芦醇预处理可上调 7,8-二氢生物蝶呤的水平。途径分析证实，7,8-二氢生物蝶呤主要与苯丙氨酸、酪氨酸和色氨酸代谢相关（影响=1，p<0.001），是多巴胺生物合成途径中酶功能的必需辅助因子。总之，氧代白藜芦醇可能通过增加 7,8-二氢生物蝶呤浓度有益于预防神经退行性疾病。
