doi: 10.3967/bes2017.047
Ginsenoside Rb1 Attenuates Isoflurane/surgery-induced Cognitive Dysfunction via Inhibiting Neuroinflammation and Oxidative Stress
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Abstract:
Objective 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. Methods 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. Results 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. Conclusion These results suggest that ginsenoside Rb1 may attenuate the isoflurane/surgery-induced cognitive impairment by inhibiting neuroinflammation and oxidative stress pending future studies. -
Key words:
- Ginsenoside Rb1 /
- Isoflurane /
- Surgery /
- Cognitive dysfunction /
- Synapse /
- Neuroinflammation /
- Oxidation stress
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Figure 1. Diagram of the experimental Design. dhe mice received Barnes Maze training from day 8 to day 11 after operation. Then, the mice received Barnes Maze probe test on day 12 and 19, respectively. Ginsenoside Rb1 treatment (60 mg/kg) started 7 days before isoflurane/surgery. Western blot analysis was performed after the behavior tests on day 19. ROS measurement was performed immediately after the isoflurane/surgery on day 0. ELISA test of IL-6 and TNF-α was performed 24 h after operation.
Figure 2. Ginsenoside Rb1 attenuated isoflurane/surgery-induced cognitive impairment. (A) Two-way ANOVA with repeated measurement showed no significant interaction (F = 0.848, P = 0.574) of treatment (isoflurane/surgery versus control condition) and time (days) on escape latency of Barnes maze training test in the mice. The isoflurane/surgery plus normal saline (NS) did not significantly increase the escape latency in Barnes Maze training test as compared to control condition plus NS in the mice. The isoflurane/surgery plus ginsenoside Rb1 did not significantly increase the escape latency in Barnes Maze training test as compared to control condition plus ginsenoside Rb1 in the mice. (B) Two-way ANOVA showed no significant interaction (F = 1.080, P = 0.306) of group and treatment on escape latency of Barnes maze 1 day after the training sessions in the mice. (C) Two-way ANOVA showed significant interaction (F = 4.246, P = 0.047) of group and treatment on escape latency of Barnes maze 8 days after the training sessions in the mice. Isoflurane/surgery plus NS increased the escape latency as compared to control condition. Ginsenoside Rb1 attenuated the isoflurane/surgery induced the escape latency prolongation as compared to isoflurane/surgery plus NS. *P < 0.05 compared with control condition plus NS. #P < 0.05 compared with isoflurane/surgery plus NS. N = 10 in each group. Rb1, ginsenoside Rb1; NS, normal saline; I/S, isoflurane/surgery.
Figure 3. Ginsenoside Rb1 mitigated the reductions in PSD-95 and SVP levels induced by isoflurane/surgery in the hippocampus of the mice. (A) Isoflurane/surgery (lanes 7 to 9) decreased PSD-95 levels as compared to control condition plus normal saline (lanes 1 to 3) in hippocampus of the mice. Ginsenoside Rb1 plus control condition (lanes 4 to 6) did not significantly alter PSD-95 levels as compared to control condition plus normal saline (lanes 1 to 3). However, Ginsenoside Rb1 plus isoflurane/surgery (lanes 10 to 12) led to lesser reductions of PSD-95 levels as compared to isoflurane/surgery plus normal saline (lanes 7 to 9). (B) Quantification of Western blot showed that Ginsenoside Rb1 (striped and black bar) inhibited the reduction in PSD-95 levels induced by the isoflurane/surgery (black bar). (C) Isoflurane/surgery (lanes 7 to 9) decreased SVP levels as compared to control condition (lanes 1 to 3) in hippocampus of the mice. Ginsenoside Rb1 plus control condition (lanes 4 to 6) did not significantly change SVP levels as compared to control condition (lanes 1 to 3). However, Ginsenoside Rb1 plus isoflurane/surgery (lanes 10 to 12) led to lesser reductions of SVP levels as compared to isoflurane/surgery (lanes 7 to 9). (D) Quantification of Western blot showed that Ginsenoside Rb1 (striped and black bar) inhibited the reduction in SVP levels induced by isoflurane/surgery (black bar). *P < 0.05 compared with control condition plus NS. #P < 0.05 compared with isoflurane/surgery plus NS. N = 6 in each group. Rb1, ginsenoside Rb1; NS, normal saline; I/S, isoflurane/surgery.
Figure 4. Ginsenoside Rb1 mitigated the elevation of IL-6 and TNF-α levels induced by isoflurane/surgery in the hippocampus of the mice. (A) ELISA showed that isoflurane/surgery plus normal saline (black bar) significantly increased IL-6 levels in hippocampus of the mice as compared to control condition (white bar) at 24 h after isoflurane/surgery. Treatment with ginsenoside Rb1 alone (white and striped bar) did not significantly change IL-6 levels as compared to control condition (white bar). Ginsenoside Rb1 mitigated the elevationofIL-6 levels induced by the isoflurane/surgery. (B) ELISA showed that isoflurane/surgery plus normal saline (black bar) significantly increased TNF-α levels in hippocampus of the mice as compared to control condition (white bar) at 24 h after isoflurane/surgery. Treatment with ginsenoside Rb1 alone (white and striped bar) did not significantly change TNF-α levels as compared to control condition (white bar). Ginsenoside Rb1 mitigated the elevation of TNF-α levels induced by isoflurane/surgery. *P < 0.05 compared with control condition plus NS. #P < 0.05 compared with isoflurane/surgery plus NS. N = 6 in each group. Rb1, ginsenoside Rb1; NS, normal saline; I/S, isoflurane/surgery.
Figure 5. Ginsenoside Rb1 mitigated the elevation of ROS levels Induced by isoflurane/surgery in the hippocampus of the Mice. ELISA showed that isoflurane/surgery plus normal saline (black bar) significantly increased ROS levels in hippocampus of the mice as compared to control condition (white bar) immediately after isoflurane/ surgery. Treatment with ginsenoside Rb1 alone (white and striped bar) did not significantly change ROS levels as compared to control condition (white bar). Ginsenoside Rb1 mitigated the elevation of ROS levels induced by the isoflurane/surgery. *P < 0.05 compared with control condition plus NS. #P < 0.05 compared with isoflurane/surgery plus NS. N = 6 in each group. Rb1, ginsenoside Rb1; NS, normal saline; I/S, isoflurane/surgery.
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