Prevention of Postoperative Fatigue Syndrome in Rat Model by Ginsenoside Rb1 <i>via</i> Down-Regulation of Inflammation along the NMDA Receptor Pathway in the Hippocampus

Abstract

Postoperative fatigue syndrome (POFS) is a common complication which decelerates recovery after surgery. The present study investigated the anti-fatigue effect of ginsenoside Rb1 (GRb1) through the inflammatory cytokine-mediated N-methyl-D-aspartate (NMDA) receptor pathway. A POFS rat model was created by major small intestinal resection and assessed with an open field test. Real-time quantitative polymerase chain reaction, western blot analysis, high performance liquid chromatography and a transmission electron microscopic analysis were used to determine typical biochemical parameters in the hippocampus. Our results showed that POFS rats exhibited fatigue associated with an increased expression of inflammatory cytokines and NMDA receptor 1, higher (kynurenine)/(tryptophan) and (kynurenine)/(kynurenic acid) on postoperative days 1 and 3, and an increased expression of indoleamine 2,3-dioxygenase (IDO) on postoperative day 1. Degenerated neurons were found in the hippocampus of POFS rats. The NMDA receptor antagonist MK801 had a significant effect on central fatigue on postoperative day 1. GRb1 had no effect on IDO or tryptophan metabolism, but exhibited a significant effect on POFS by inhibiting the expression of inflammatory cytokines and NMDA receptor 1. These data suggested that inflammatory cytokines could activate tryptophan metabolism to cause POFS through the NMDA receptor pathway. GRb1 had an anti-fatigue effect on POFS by reducing inflammatory cytokines and NMDA receptors.

M30 Antagonizes Indoleamine 2,3-Dioxygenase Activation and Neurodegeneration Induced by Corticosterone in the Hippocampus

“…In our study, we have shown that there were significant elevations in the inflammatory cytokines which is pivotal to the activation of IDO-1 which subsequently reduced the level of 5-HT in the hippocampus. Our observation is in agreement with the previous reports demonstrating the activation of IDO-1 accompanied by the reduction in the 5-HT content in response to immune activation in the hippocampus of rat [49, 50]. Therefore, it should be IDO-1 instead of TDO-2 mediating the tryptophan breakdown in the hippocampus.…”

Beneficial effect of compound essential oil inhalation on central fatigue

“…Locomotor activity was composed by horizontal activity and vertical activity. It has been reported that physical fatigue could decrease locomotor activity [ 58 ], unfortunately, few literature reported the changes in locomotor activity during central fatigue. The measures of horizontal activity in this study composing total distance travelled, number of crossing squares, maximum distance travelled, and the mean velocity, it is showed a significant increase in CSD rats, and a decreasing trend after inhalation treatment without statistical significance.…”

Involvement of N-Methyl-D-Aspartic Acid Receptor and DL-α-Amino-3-Hydroxy-5- Methyl-4-Isoxazole Propionic Acid Receptor in Ginsenosides Rb1 and Rb3 against Oxygen-Glucose Deprivation-Induced Injury in Hippocampal Slices from Rat

“…Peng et al [23] reported that ginsenoside Rb3 inhibited NMDA-evoked peak current in hippocampal neurons, and Ca 2+ -induced desensitization of NMDA current was facilitated. Ginsenoside Rb1 had an anti-fatigue effect on postoperative fatigue syndrome by inhibiting the expression of inflammatory cytokines and NMDA receptors [24]. It is suggested that the effects of ginsenosides Rb3 and Rb1 are partly mediated by the inactivation of the NMDA receptor.…”