1. Academic Validation
  2. Gastrodin prevents myocardial injury in sleep-deprived mice by suppressing ferroptosis through SIRT6

Gastrodin prevents myocardial injury in sleep-deprived mice by suppressing ferroptosis through SIRT6

  • Naunyn Schmiedebergs Arch Pharmacol. 2024 Jun 19. doi: 10.1007/s00210-024-03230-4.
Yi Wu # 1 Yuping Miao # 1 Yin Cao 2 3 Zipeng Gong 4 5
Affiliations

Affiliations

  • 1 School of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Road, Xinzhan Area, Hefei, 230012, China.
  • 2 School of Pharmacy, Anhui University of Chinese Medicine, 350 Longzihu Road, Xinzhan Area, Hefei, 230012, China. cy306@sina.com.
  • 3 State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, 4 Beijing Road, Guiyang, 550014, Guizhou Province, China. cy306@sina.com.
  • 4 State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Provincial Key Laboratory of Pharmaceutics, Guizhou Medical University, 4 Beijing Road, Guiyang, 550014, Guizhou Province, China. gzp4012607@126.com.
  • 5 Key Laboratory of Basic Pharmacology of Ministry of Education, Zunyi Medical University, Zunyi, 563000, China. gzp4012607@126.com.
  • # Contributed equally.
Abstract

Gastrodin (GAS), a bioactive compound derived from the orchid plant Gastrodia elata, exhibits numerous pharmacological effects. However, its effect on sleep deprivation (SD)-induced cardiac injury and the mechanisms are unknown. This study established SD mice model using a modified multiple platform water method and induced Ferroptosis model in H9c2 cells using Erastin. The heart rate of mice was measured, and myocardial and mitochondrial structures were visualized using hematoxylin and eosin (H&E) staining and transmission electron microscopy (TEM). Myocardial injury, oxidative stress Indicators, and Fe2+ levels were detected by the kit method. The Reactive Oxygen Species (ROS) levels were detected by immunofluorescence, and SIRT6 and ferroptosis-associated protein expression levels were detected by Western blot. Reduced heart rate and abnormalities in myocardial tissue and mitochondrial structure were ameliorated in the SD group of mice after GAS treatment. GAS treatment reduced ROS levels in Erastin-induced H9c2 cells. GAS treatment reduced atrial natriuretic peptide (ANP), creatine kinase (CK), Lactate Dehydrogenase (LDH), malondialdehyde (MAD), and Fe2+ levels, and increased superoxide dismutase (SOD) and glutathione (GSH) levels in the SD and Erastin groups. Western blot showed that GAS treatment increased the expression of Sirtuin 6 (SIRT6), solute carrier family 7 member 11 (SLC7A11), and Glutathione Peroxidase 4 (GPX4) and decreased the expression of P53 in SD and Erastin groups. The SIRT6 Inhibitor OSS_128167 (OSS) reversed GAS treatment of Erastin-induced Ferroptosis in H9c2 cells. These observations propose that GAS prevents myocardial injury in sleep-deprived mice by suppressing Ferroptosis through SIRT6.

Keywords

Ferroptosis; Gastrodin; Myocardial injury; SIRT6; Sleep deprivation.

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