2. Academic Validation
  3. Chinese traditional formula Kaixin San suppressed ferroptosis of hippocampal neurons and cardiomyocytes in mice with paradoxical sleep deprivation

Chinese traditional formula Kaixin San suppressed ferroptosis of hippocampal neurons and cardiomyocytes in mice with paradoxical sleep deprivation

  • J Ethnopharmacol. 2022 Dec 15;304:116034. doi: 10.1016/j.jep.2022.116034.
Yin Cao 1,  Mingrui Li 1,  Lihua Gu 2,  Xin Zhao 2,  An Zhou 1,  Yuping Miao 1,  Yi Wu 1,  Zunji Ke 3,  Rongfeng Hu 4,  Zhengtao Wang 5,  Xiaojun Wu 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, Hefei, 230038, China.
  • 2 Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, The Sate Administration of TCM (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 3 Academy of Integrative Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China.
  • 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, Hefei, 230038, China. Electronic address: rongfenghu@ahtcm.edu.cn.
  • 5 Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, The Sate Administration of TCM (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: ztwang@shutcm.edu.cn.
  • 6 Shanghai Key Laboratory of Compound Chinese Medicines, The Ministry of Education (MOE) Key Laboratory for Standardization of Chinese Medicines, The Sate Administration of TCM (SATCM) Key Laboratory for New Resources and Quality Evaluation of Chinese Medicine, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China. Electronic address: xiaojunwu320@126.com.
PMID: 36529245 DOI: 10.1016/j.jep.2022.116034
Abstract

Ethnopharmacological relevance: Kaixin San (KXS) is one of the most famous traditional Chinese formulas prescribed by Sun Simiao in 652 Christian era. It is composed of Panax ginseng C.A.Mey, Polygala tenuifolia, Poria cocos and Acorus calamus var. angustatus Besser. KXS is widely used for the treatment of emotion-thought disease, such as settling fright, quieting the spirit and nourishing the heart. However, whether KXS benefits hippocampal neurons and myocardial cells of mice impaired by paradoxical sleep deprivation (PSD) and its mechanism remains unclear.

Aim of the study: This study was aimed to investigate the effect of KXS on hippocampal neuron and cardiac Ferroptosis in rapid-eye-movement (REM) sleep deprived mice and clarify its potential mechanism.

Materials and methods: PSD was induced by a modified multi-platform method. Morris water maze (MWM) was used to detect the ability of learning and memory. Cardiac morphological changes were assessed by hematoxylin and eosin (HE) staining. Heart rate was detected by a PowerLab multichannel physiological recorder. Serum levels of atrial natriuretic peptide (ANP) and Lactate Dehydrogenase (LDH) were measured with biochemical kits. Transmission electron microscopy (TEM), immunofluorescent, and Western blotting analysis were used to observe the process and pathway of ferrotosis in hippocampus tissue and heart tissue of PSD mice.

Results: KXS administration improved the impaired learning and memory of PSD mice. It prevented the damage of mitochondria in the hippocampus and heart of PSD mice. KXS also alleviated the myocardial injury, such as morphological damage, abnormal heart rate, serum ANP, and serum LDH induced by PSD. Further study disclosed that KXS reversed the expressions of proteins involved in Ferroptosis such as TFRC, SLC7A11/xCT, GPX-4, ACSL4, and FTH1 in hippocampus and heart tissues.

Conclusions: KXS improved learning and memory of mice with REM sleep deprivation, which was closely associated with suppressed Ferroptosis in hippocampal neurons and myocardiocytes.

Keywords

Ferroptosis; Kaixin San; Myocardiocyte; Neuron; Sleep deprivation.

Figures
Products