2. Academic Validation
  3. L-theanine prevents myocardial injury in sleep‑deprived mice by suppressing ferroptosis through SIRT1

L-theanine prevents myocardial injury in sleep‑deprived mice by suppressing ferroptosis through SIRT1

  • Naunyn Schmiedebergs Arch Pharmacol. 2025 May 6. doi: 10.1007/s00210-025-04206-8.
Xuanxuan Huang # 1,  Xinglong Lu # 1,  Yi Wu 1,  Zhenghua Wu 1,  Mingrui Li 1,  Yuping Miao 1,  Zhongwen Xie 2,  Zipeng Gong 3,  Yin Cao 4 5 6
Affiliations

Affiliations

  • 1 Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine, 350 Longzihu Road, Xinzhan Area, Hefei, 230012, China.
  • 2 State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, 130 Changjiang West Road, Hefei, 230036, China. zhongwenxie@ahau.edu.cn.
  • 3 State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guian New Area 561113, 0851-86908468, 4 Beijing Road, Guiyang City, 550004, Guizhou Province, China. gzp4012607@126.com.
  • 4 Key Laboratory of Xin'an Medicine, Ministry of Education, Anhui Province Key Laboratory of R&D of Chinese Medicine, Anhui University of Chinese Medicine, 350 Longzihu Road, Xinzhan Area, Hefei, 230012, China. cy306@sina.com.
  • 5 State Key Laboratory of Tea Plant Biology and Utilization, Anhui Agricultural University, 130 Changjiang West Road, Hefei, 230036, China. cy306@sina.com.
  • 6 State Key Laboratory of Discovery and Utilization of Functional Components in Traditional Chinese Medicine, Engineering Research Center for the Development and Application of Ethnic Medicine and TCM (Ministry of Education), Guizhou Medical University, Guian New Area 561113, 0851-86908468, 4 Beijing Road, Guiyang City, 550004, Guizhou Province, China. cy306@sina.com.
  • # Contributed equally.
PMID: 40328913 DOI: 10.1007/s00210-025-04206-8
Abstract

Green tea is obtained from Camellia sinensis, and its role in promoting heart health has been widely recognized in traditional Chinese medicine. L-theanine, one of the main bioactive components of green tea, has antioxidant and cardiovascular protective effects. However, the effects of L-theanine on myocardial cells in sleep-deprived mice and its potential mechanisms have not been clearly elucidated. This study utilized a modified multiple-platform water environment method to establish an SD model and induce a Ferroptosis model in H9c2 cells pretreated with erastin. The cardiac function parameters of mice were assessed using a small animal super-resolution ultrasound imaging system. H&E staining was used to evaluate pathological changes in tissue structure and cell morphology, while transmission electron microscopy (TEM) was employed to observe the extent of mitochondrial damage. Biochemical assays were employed to quantify myocardial damage markers, oxidative stress indicators, and Fe2⁺ concentrations, while immunofluorescence imaging assessed Reactive Oxygen Species (ROS) levels. Western blot was used to analyze the expression of SIRT1 and proteins related to Ferroptosis. The results demonstrate that L-theanine alleviates SD-induced tachycardia in mice, restores myocardial and mitochondrial integrity, and reduces oxidative damage markers, including ROS and Fe2⁺ in H9c2 cells. Furthermore, L-theanine reversed the abnormal expression of SIRT1 and ferroptosis-related proteins in cardiac tissue and H9c2 cells induced by SD and erastin. Notably, the SIRT1 Inhibitor EX-527 can counteract the protective effect of L-theanine against Ferroptosis in cardiomyocytes. These findings highlight that L-theanine mitigates SD-induced cardiac injury primarily by suppressing Ferroptosis through SIRT1 in cardiomyocytes.

Keywords

Ferroptosis; L-theanine; Myocardial injury; SIRT1; Sleep deprivation.

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