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Involvement of Autophagy in the Protective Effects of Ginsenoside Rb1 in a Rat Model of Traumatic Brain Injury

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European Journal of Drug Metabolism and Pharmacokinetics Aims and scope Submit manuscript

Abstract

Background and Objectives

No treatment modalities have been identified to prevent neuron damage induced by traumatic brain injury (TBI). The objective of this study was to investigate whether ginsenoside Rb1 (GS-Rb1) could be utilized to exert neuroprotective effects in TBI.

Methods

Lateral fluid percussion injury (LFPI) was used to induce an experimental TBI model. Lewis rats were divided into a GS-Rb1 group (5, 10, 20 mg/kg, intraperitoneally injected daily), a sham group, and a vehicle group. Neurological impairments were assessed with brain water content, Evans blue extravasation, neurological deficit scores, and Morris water maze test. TUNEL and NeuN staining were utilized to detect neuron apoptosis. The relative expression of apoptosis- and autophagy-relevant molecules were assayed with real-time PCR and western blot.

Results

GS-Rb1 inhibited TBI-induced brain edema and Evans blue extravasation in a dose-dependent manner. Furthermore, GS-Rb1 improved neurological impairments with diminished neurological deficit scores, decreased escape latencies, increased time in the target quadrant, and increased number of platform site crossings. GS-Rb1 protected against neuron apoptosis with downregulated Bax expression and upregulated Bcl-2 expression. It was worth noting that TBI increased the LC3II/LC3I ratio and upregulated the relative expression of Beclin-1, Atg-7, and Atg-3; moreover, TBI downregulated the relative expression of P62. The administration of GS-Rb1 further strengthened the relative expression of autophagy-related molecules.

Conclusions

GS-Rb1 alleviates neurological impairments induced by TBI with upregulated autophagy.

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Author information

Author notes

  1. Shufeng Zou, Wei Chen, and Han Ding contributed equally to this work.

Authors and Affiliations

  1. Department of Neurosurgery, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China

    Shufeng Zou, Wei Chen, Han Ding, Yuanyuan Qi, Jun Fu, Jian Duan & Jiugeng Feng

  2. Department of Neurosurgery, Shanghai East Hospital, School of Medicine, Tongji University, Pudong New Area, Shanghai, 200120, China

    Wei Chen & Zhigang Wang

  3. Department of Neurosurgery, The People’s Hospital of Shanghai Pudong New Area, Shanghai, 201299, China

    Dabin Ren

  4. Department of Clinical Laboratory, The First Affiliated Hospital of Nanchang University, Nanchang, 330006, Jiangxi, China

    Bixia Jiang

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  1. Shufeng Zou
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Corresponding authors

Correspondence to Jian Duan, Bixia Jiang or Jiugeng Feng.

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Funding

The study was supported by the Key R & D project of Jiangxi Provincial Department of Science and Technology (20203BBGl73172); the scientific research project of Jiangxi Provincial Department of Education (GJJ200165, GJJ190022); the key youth project of Jiangxi Natural Science Foundation (20202ACBL216005); the National Natural Science Foundation of China (NSFC: 82171366, 81960236).

Conflict of interest

The authors declare that they had no conflicts of interest.

Ethics approval

The study protocol was approved by the Animal Ethics Committee of the First Affiliated Hospital of Nanchang University. All institutional guidelines for the care of the laboratory animals were followed.

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Availability of data and material

Data could be obtained upon reasonable request to the corresponding authors.

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Author contributions

S.Z., W.C., H.D., Y.Q., Z.W., J.F., D.R., J.D., and B.J. conducted the experiments, and collected and analyzed the data; S.Z., W.C., J.D., B.J., and J.F. conceived the study; S.Z., W.C., H.D., Y.Q., Z.W., J.F., D.R., J.D., B.J., and J.F. wrote the original manuscript and revised the paper.

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Zou, S., Chen, W., Ding, H. et al. Involvement of Autophagy in the Protective Effects of Ginsenoside Rb1 in a Rat Model of Traumatic Brain Injury. Eur J Drug Metab Pharmacokinet 47, 869–877 (2022). https://doi.org/10.1007/s13318-022-00799-0

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