Abstract
The traditional Chinese medicine (TCM) decoction Si-Ni-San (SNS) has been utilised for millennia to improve physiological coordination of the functions of the liver and spleen, which are regarded as the main pathological organs of central fatigue in TCM. This study evaluates the effect of a modified SNS (MSNS) formula on central fatigue in rats and explores molecular changes associated with hippocampal mitochondrial biogenesis. Central fatigue was induced through a 21-day sleep deprivation protocol. We assessed MSNS's effects on behaviour, blood and liver biomarkers, and mitochondrial ultrastructure. We found that MSNS could reverse various signs of central fatigue such as its effects on hippocampal gene and protein expression levels of sirtuin 1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1α (PGC-1α), and nuclear respiratory factor 1 (NRF1). We also observed evidence of MSNS decreasing central fatigue, such as decreasing creatine kinase activity, decreasing levels of malondialdehyde and blood urea nitrogen, increasing lactate dehydrogenase and superoxide dismutase activities, increasing mitochondrial DNA copy number, and reversing mitochondrial ultrastructure changes. These findings suggest that MSNS can ameliorate central fatigue and that its molecular mechanism involves mitochondrial biogenesis enhancement mediated by hippocampal SIRT1, PGC-1α, and NRF1.
Highlights
Central fatigue (CF) is the failure to initiate and sustain attention and physical activities requiring self-motivation [1]
We aimed to evaluate the effects of modified SNS (MSNS) by inducing a rat model of CF through sleep deprivation [26] and using it to test the effects of low-dose MSNS (LDM), medium-dose MSNS (MDM), and high-dose MSNS (HDM)
Accumulating evidence suggests that the hippocampal mitochondrial function can directly influence CF by affecting energy metabolism and oxidative processes
Summary
Central fatigue (CF) is the failure to initiate and sustain attention and physical activities requiring self-motivation (as opposed to external stimulation) [1]. It has become a major complaint with the fast pace of modern life. Numerous studies have investigated skeletal muscle metabolism in CF, but few have investigated the changes in cerebral energy production and oxidative function that play vital roles in CF. The exact mechanism of CF is unclear, a feeling of low energy is always involved, which suggests that CF is closely related to energy metabolism and oxidative function in the central nervous system [3]. Since the brain relies on aerobic metabolism, cerebral oxygen tension is the basic guarantee of brain function and this process mainly relies on brain mitochondrial function [4]
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