Cerebral energy deficiency is a key pathophysiologic cascade that results in neuronal injury and
necrosis after
ischemic stroke. Shengui Sansheng San (SSS) has been used to treat
stroke for more than 300 years. In present study, we investigated the therapeutic efficacy and mechanism of SSS extraction on cerebral energy deficiency post-
stroke. In permanent
middle cerebral artery occlusion (pMCAo) model of rats, it suggested that SSS extraction in dose-dependent manner improved neurological function, cerebral blood flow (CBF), 18F-2-deoxy-glucose uptake and the density and diameter of alpha smooth muscle actin (α-SMA) positive vasculature in ipsilateral area, as well as decreased infarcted volume. Meanwhile, the metabolomics study in cerebrospinal fluid (CSF) was performed by using 5-(diisopropylamino)amylamine (DIAAA) derivatization-UHPLC-Q-TOF/MS approach. Eighty-eight endogenous metabolites were identified, and mainly involved in
citrate cycle,
fatty acid biosynthesis, aminoacyl-
tRNA biosynthesis,
amino acids metabolism and biosynthesis, etc. The remarkable increase of
citrate in CSF
after treatment with three dosages indicated that the therapeutic mechanism of SSS extraction might be related with
citrate cycle. Simultaneously, it showed that high dosage group significantly increased peripheral
blood glucose level, the expressions of
glucose transporter (GLUT) 1, GLUT3, and monocarboxylic
acid transporter 1 (MCT1), which contributed to the transportation of
glucose and
lactate. By the regulations of phosphorylated
pyruvate dehydrogenase E1-alpha (p-PDHA1),
acetyl CoA synthetase and
citrate synthetase (CS), the levels of
citrate and its upstream molecules (
pyruvate and
acetyl CoA) in peri-
infarction zone further enhanced, which ultimately caused the massive yield of
adenosine triphosphate (
ATP). Our study first demonstrated that SSS extraction could ameliorate cerebral energy deficiency after
ischemia by
citrate cycle, which is characterized by the enhancements of
glucose supply, transportation, utilization, and metabolism.