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

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.

• Authors: Shufeng Zou, Wei Chen, Han Ding, Yuanyuan Qi, Zhigang Wang, Jun Fu, Dabin Ren, Jian Duan, Bixia Jiang, Jiugeng Feng
• Journal: European journal of drug metabolism and pharmacokinetics (Eur J Drug Metab Pharmacokinet) Vol. 47 Issue 6 Pg. 869-877 (Nov 2022) ISSN: 2107-0180 [Electronic] France
• PMID: 36197653 (Publication Type: Journal Article)
• Copyright: © 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.

Chemical References

• ginsenoside Rb1
• Evans Blue

Topics

• Rats
• Animals
• Evans Blue (pharmacology)
• Rats, Inbred Lew
• Autophagy
• Brain Injuries, Traumatic (drug therapy, metabolism)