GP-17 improves PTSD-like behaviour in rats by affecting AKT/NF-κB-mediated neuroinflammation

doi:10.3877/cma.j.issn.2095-9141.2025.02.004

Abstract

Abstract:

Objective

To investigate the effect of gypenoside ⅩⅦ （GP-17） on neuroinflammation after post-traumatic stress disorder （PTSD） and explore its mechanism of action.

Methods

Twenty-four 8-week-old male SD rats were randomly divided into Control group， SPS group， GP-17 low-dose group（1 mg/kg）， and GP-17 high-dose group （4 mg/kg）， with 6 rats in each group. A single prolonged stress（SPS） modelling was carried out in all groups except Control group， followed by intraperitoneal injection of 1， 4 mg/kg in GP-17 treatment group， and equal amount of saline was given intraperitoneally in Control group as well as in SPS group. After 7 d of SPS modeling， the fear status of PTSD rats was assessed using a capture refusal score and a fear condition test. Enzyme linked immunosorbent assay （ELISA） kit was used to detect the protein expression of interleukin （IL）-1β， IL-6， and tumor necrosis factor α （TNF-α），RT-qPCR was used to detect the mRNA expression of the above inflammatory factors. Immunofluorescence staining was used to detect the expression of microglial polarization marker INOS. Western blot was used to detect the relative expression levels of pathway related proteins phospho-protein kinase B （p-AKT），phospho-nuclear factor kappa B （p-P65）， and phospho-inhibitor of nuclear factor-κB kinase α/β （p-IKKα/β）.

Results

After 7 d of SPS modeling， the refusal score and freezing time of SPS group， GP-17 low-dose group， and high-dose group were significantly higher than those of the control group. The refusal score and freezing time of the GP-17 low-dose group and high-dose group were significantly lower than those of the SPS group， and the differences were statistically significant （P＜0.05）. ELISA and RT-qPCR results showed that the expression of IL-1β， IL-6， and TNF-α in the brain tissue of GP-17 low-dose and highdose groups after modeling was lower than that of SPS group at the RNA and protein levels （P＜0.05）， with the exception of IL-1β expression in the low-dose GP-17 group （P＞0.05）. Immunofluorescence results showed that the expression of the M1 polarization marker INOS in microglia in GP-17 low-dose and highdose groups was significantly lower than that in SPS group （P＜0.05）. Western blot results showed that compared with the SPS group， the expression levels of p-IKKα/β， p-AKT， and p-P65 were significantly decreased in both GP-17 high-dose group and low-dose groups （P＜0.05）， with the exception of the expression level of p-IKKα/β in the GP-17 low-dose group （P＞0.05）.

Conclusions

GP-17 attenuates panic behaviour and inhibits the expression of IL-1β， IL-6 and TNF-α in prefrontal cortex of PTSD rats，and also inhibits the expression of M1-type marker INOS in BV₂ cells， which exerts neuroprotective effects， and the mechanism of its action may be related to the inhibition of neuroinflammation mediated by the AKT/NF-κB inflammatory pathway.

Key words: Post-traumatic stress disorder, Gypenoside ⅩⅦ, Protein kinase B, Nuclear factor κB, Neuroinflammation

Shuying Wang, Yitai Yang, Zemeng Li, Dangli Ren, Jingjing Wang, Yueyang Chen, Huimin Zhang, Hongtao Sun. GP-17 improves PTSD-like behaviour in rats by affecting AKT/NF-κB-mediated neuroinflammation[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2025, 11(02): 94-102.

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Figures/Tables 5

Tab.1 Comparison of rejection score and freezing time after modeling in 4 groups of rats

组别	只数	拒俘评分[分， M(P₂₅,P₇₅)]	冻结时间(s,x̄±s)
对照组	6	0.000(0.000,1.000)	2.662±0.466
SPS组	6	5.000(4.000,5.000)^a	47.210±3.920^a
GP-17低剂量组	6	4.000(3.000,4.000)^ab	31.272±1.643^ab
GP-17高剂量组	6	2.000(1.750,2.000)^abc	17.180±3.282^abc
H/F值		21.253	300.867
P值		<0.001	<0.001

Fig.1 Comparison of the concentrations of IL-1β， IL-6， and TNF-α in the prefrontal cortex of four groups of rats

Fig.2 Comparison of expression levels of IL-1β mRNA， IL-6 mRNA， and TNF-α mRNA in the prefrontal cortex of four groups of rats

Fig.3 Expression levels of the M1 marker INOS in four groups of BV₂ cells

Fig.4 Comparison of p-P65， p-AKT， and p-IKKα/β protein expression in 4 groups of rats

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