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Isoflurane/surgery (I/S) may induce neurocognitive disorders, but detailed mechanisms and appropriate treatment remain largely unknown. This experiment was designed to determine whether ginsenoside Rg1 could attenuate I/S-induced neurocognitive disorders and Sirtuin3 (Sirt3) dysfunction. C57BL/6J male mice received 1.4% isoflurane plus abdominal surgery for 2 h. Ginsenoside Rg1 10 mg/kg was intraperitoneally given for 8 days before surgery. Neurocognitive function was assessed by the Barnes Maze test. Levels of reactive oxygen species (ROS), oxygen consumption rate (OCR), mitochondrial membrane potential (MMP), expression and deacetylation activity of Sirt3 in the hippocampus tissues were measured. Results showed that I/S induced hippocampus-dependent learning and memory impairments, with increased ROS levels, and reduced OCR, MMP, and expression and deacetylation activity of Sirt3 in hippocampus tissues. Ginsenoside Rg1 treatment before I/S intervention significantly ameliorated learning and memory performance, reduced ROS levels and improved the OCR, MMP, expression and deacetylation activity of Sirt3. In conclusion, this experiment demonstrates that ginsenoside Rg1 treatment can attenuate I/S-induced neurocognitive disorders and Sirt3 dysfunction.

Anesthetic isoflurane plus surgery has been reported to induce cognitive impairment. The underlying mechanism and targeted intervention remain largely to be determined. Ginsenoside Rb1 was reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rb1 can attenuate isoflurane/surgery-induced cognitive dysfunction via inhibiting neuroinflammation and oxidative stress.Five-months-old C57BL/6J female mice were treated with 1.4% isoflurane plus abdominal surgery for two hours. Sixty mg/kg ginsenoside Rb1 were given intraperitoneally from 7 days before surgery. Cognition of the mice were assessed by Barnes Maze. Levels of postsynaptic density-95 and synaptophysin in mice hippocampus were measured by Western blot. Levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in mice hippocampus were measured by ELISA.Here we show for the first time that the ginsenoside Rb1 treatment attenuated the isoflurane/surgery-induced cognitive impairment. Moreover, ginsenoside Rb1 attenuated the isoflurane/surgery-induced synapse dysfunction. Finally, ginsenoside Rb1 mitigated the isoflurane/surgery-induced elevation levels of reactive oxygen species, tumor necrosis factor-α and interleukin-6 in the mice hippocampus.These results suggest that ginsenoside Rb1 may attenuate the isoflurane/surgery-induced cognitive impairment by inhibiting neuroinflammation and oxidative stress pending future studies.

The inhalation anesthetic isoflurane has been shown to induce mitochondrial dysfunction and caspase activation, which may lead to learning and memory impairment. Ginsenoside Rg1 is reported to be neuroprotective. We therefore set out to determine whether ginsenoside Rg1 can attenuate isoflurane-induced caspase activation via inhibiting mitochondrial dysfunction.We investigated the effects of ginsenoside Rg1 at concentrations of 12.5, 25, and 50 μmol/L and pretreatment times of 12 h and 24 h on isoflurane-induced caspase-3 activation in H4 naïve and stably transfected H4 human neuroglioma cells that express full-length human amyloid precursor protein (APP) (H4-APP cells). For mitochondrial dysfunction, we assessed mitochondrial permeability transition pore (mPTP) and adenosine-5'-triphosphate (ATP) levels. We employed Western blot analysis, chemiluminescence, and flowcytometry.Here we show that pretreatment with 50 µmol/L ginsenoside Rg1 for 12 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in H4-APP cells, while pretreatment with 25 and 50 µmol/L ginsenoside Rg1 for 24 h attenuated isoflurane-induced caspase-3 activation and mitochondrial dysfunction in both H4 naïve and H4-APP cells.These data suggest that ginsenoside Rg1 may ameliorate isoflurane-induced caspase-3 activation by inhibiting mitochondrial dysfunction. Pending further studies, these findings might recommend the use of ginsenoside Rg1 in preventing and treating isoflurane-induced neurotoxicity.