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

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

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

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.

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.