Shenling Baizhu San alleviates central fatigue through SIRT1-PGC-1α-Mediated mitochondrial biogenesis

Shenling Baizhu San (SLBZS) is a Traditional Chinese Medicine (TCM) formula composed of 10 medicinal herbs, historically used to strengthen the spleen, replenish qi, and alleviate fatigue-related symptoms. SLBZS originates from the 'Taiping Huimin Heji Ju Fang' of the Song Dynasty. Central fatigue (CF), a subtype of fatigue, is considered in TCM to be closely associated with spleen deficiency. However, there is currently a lack of research on SLBZS's therapeutic effects on CF and the pharmacological mechanisms underlying its potential benefits. This study aims to assess the effects of SLBZS on CF in rats induced by the Modified Multiple Platform Method (MMPM) and to elucidate the underlying mechanisms, focusing on mitochondrial biogenesis and SIRT1/PGC-1α pathway regulation. CF was induced in male Wistar rats using MMPM, involving intermittent sleep deprivation over 21 days. SLBZS was administered at low(LSLBZS), medium(MSLBZS), and high doses(HSLBZS). Chemical components of SLBZS were identified and quantified using Liquid Chromatography-Tandem Mass Spectrometry(LC-MS/MS). Behavioral tests evaluated physical performance, emotional state, and cognitive function, while serum biochemical markers, mitochondrial morphology, and the protein and gene expression levels of the SIRT1/PGC-1α pathway were analyzed to explore underlying mechanisms. A total of 141 main compounds in SLBZS were identified, comprising various components such as flavonoids, phenylpropanoids, terpenoids, among others. SLBZS significantly improved physical performance, alleviated negative emotions, and enhanced cognitive function in CF rats. Biochemically, SLBZS increased serum ATP levels and reduced fatigue-related markers. Mitochondrial analysis demonstrated that SLBZS reversed mitochondrial degeneration, increased mitochondrial number, and increased mtDNA copy number in the hippocampus. Furthermore, SLBZS upregulated SIRT1/PGC-1α pathway expression at both the protein and gene levels in the hippocampus. Notably, the HSLBZS group demonstrated particularly pronounced effects. SLBZS significantly alleviates CF symptoms enhances mitochondrial function via upregulating the SIRT1/PGC-1α pathway, positioning it as a promising alternative for CF management by addressing both its physiological and symptomatic aspects. [Display omitted]