表没食子儿茶素没食子酸酯通过调节黑腹果蝇的蛋氨酸代谢和表观遗传稳态来缓解高同型半胱氨酸血症
Epigallocatechin gallate alleviates hyperhomocysteinemia by regulating methionine metabolism and epigenetic homeostasis in Drosophila melanogaster.
摘要(中文译文)
高同型半胱氨酸血症(HHcy)的特征是甲硫氨酸和一碳代谢紊乱。尽管表没食子儿茶素没食子酸酯(EGCG)能够降低同型半胱氨酸水平,但其在体内如何调控甲硫氨酸代谢,尤其是在肠道层面,仍不清楚。本研究旨在确定EGCG是否通过调节甲硫氨酸可利用性来缓解HHcy。采用高甲硫氨酸饮食在黑腹果蝇中建立HHcy模型。首先使用代谢和生理指标评估茶提取物和儿茶素的效果。随后利用靶向代谢组学和LC-MS/MS对甲硫氨酸代谢及N-EGCG的形成进行表征。最后进行转录组学和表观遗传学分析,以检查下游调控变化。含有最高EGCG水平的绿茶对HHcy表现出最强的保护作用。EGCG以剂量依赖性方式显著改善HHcy表型。它将同型半胱氨酸水平降低约55%。这表明其对甲硫氨酸代谢有强烈影响。它还显著延长了寿命。重要的是,EGCG使肠道甲硫氨酸水平降低约58%,并促进体内N-EGCG的形成。这些变化伴随着代谢通路的恢复。转录和表观遗传模式也恢复正常。EGCG通过限制肠道甲硫氨酸可利用性和恢复一碳代谢来缓解HHcy。本研究揭示了一种与肠道相关的代谢机制。它将膳食多酚与全身代谢调控联系起来。它还突出了HHcy膳食干预的潜在靶点。
Abstract
Hyperhomocysteinemia (HHcy) is characterized by disrupted methionine and one-carbon metabolism. Although epigallocatechin gallate (EGCG) can lower homocysteine levels, how it regulates methionine metabolism in vivo, especially at the intestinal level, remains unclear. This study aimed to determine whether EGCG alleviates HHcy by modulating methionine availability. An HHcy model was established in Drosophila melanogaster using a high-methionine diet. The effects of tea extracts and catechins were first evaluated using metabolic and physiological indicators. Methionine metabolism and N-EGCG formation were then characterized using targeted metabolomics and LC-MS/MS. Finally, transcriptomic and epigenetic analyses were performed to examine downstream regulatory changes. Green tea, which contains the highest EGCG level, showed the strongest protection against HHcy. EGCG significantly improved HHcy phenotypes in a dose-dependent manner. It reduced homocysteine levels by approximately 55%. This indicates a strong effect on methionine metabolism. It also significantly extended lifespan. Importantly, EGCG reduced intestinal methionine levels by approximately 58% and promoted the formation of N-EGCG in vivo. These changes were accompanied by recovery of metabolic pathways. Transcriptional and epigenetic patterns were also normalized. EGCG alleviates HHcy by limiting intestinal methionine availability and restoring one-carbon metabolism. This study reveals a gut associated metabolic mechanism. It links dietary polyphenols to systemic metabolic regulation. It also highlights a potential target for dietary intervention of HHcy.
如何引用
AMA
Yuxuan Zhao, Jingyimei Liang, Jesus Simal-Gandara, Hui Cao. Epigallocatechin gallate alleviates hyperhomocysteinemia by regulating methionine metabolism and epigenetic homeostasis in Drosophila melanogaster.. Phytomedicine : international journal of phytotherapy and phytopharmacology. 2026; doi:10.1016/j.phymed.2026.158230.
APA
Yuxuan Zhao, Jingyimei Liang, Jesus Simal-Gandara, Hui Cao (2026). Epigallocatechin gallate alleviates hyperhomocysteinemia by regulating methionine metabolism and epigenetic homeostasis in Drosophila melanogaster.. Phytomedicine : international journal of phytotherapy and phytopharmacology. https://doi.org/10.1016/j.phymed.2026.158230
GB/T 7714
Yuxuan Zhao, Jingyimei Liang, Jesus Simal-Gandara, Hui Cao. Epigallocatechin gallate alleviates hyperhomocysteinemia by regulating methionine metabolism and epigenetic homeostasis in Drosophila melanogaster.[J]. Phytomedicine : international journal of phytotherapy and phytopharmacology, 2026 doi:10.1016/j.phymed.2026.158230.
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