Rhubarb attenuates cerebral edema via inhibition of the extracellular signal-regulated kinase pathway following traumatic brain injury in rats

大黄通过抑制大鼠脑创伤后细胞外信号调节激酶通路减轻脑水肿

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作者:Zhaoyu Yang, Rong Fan, Peng Sun, Hanjin Cui, Weijun Peng, Jiekun Luo, Chunhu Zhang, Xingui Xiong, Wei Huang, Wei Liu

Background

Rhubarb is a traditional Chinese medicine for treating traumatic brain injury (TBI).

Conclusions

Rhubarb alleviates the edema by restraining the ERK signaling pathway. Our results contribute to the validation of the traditional use of rhubarb in the treatment of TBI and its mechanism. Summary: The aim of this study was to explore the potential mechanism of rhubarb by suppressing extracellular signal-regulated kinase to ameliorate brain edema. Results: Rhubarb ameliorates edema caused by traumatic brain injury by inhibiting the ERK/Matrix metalloproteinase 9/zonula occluden-1 signaling pathway. Abbreviations used: TBI: Traumatic brain injury, ERK: Extracellular signal-regulated kinase pathway, MMP-9: Matrix metalloproteinase 9, ZO-1: Zonula occluden-1, BBB: Blood-brain barrier, PCR: Polymerase chain reaction, TCM: Traditional Chinese medicine, MAPKs: Mitogen-activated protein kinases, CCI: Controlled cortical impact, DL: Rhubarb 3 g/kg in distilled water, DH: Rhubarb 12 g/kg in distilled water, EB: Evans blue, IOD: Integral optical density, MEK: Mitogen extracellular kinase, MMPs: Matrix metalloproteinases, NADPH: Nicotinamide adenine dinucleotide phosphate: ROS, reactive oxygen species.

Methods

Sprague-Dawley rats were separated into four groups at random. One group received 3 g/kg rhubarb, and another group received 12 g/kg rhubarb, and the vehicle group and sham group were administered the same dose of saline solution. The blood-brain barrier disruption and edema were detected by Evans blue extravasation and water content, respectively. ERK, Matrix metalloproteinase 9 (MMP-9), and zonula occluden-1 (ZO-1) in the damaged tissue were measured by western blot analysis and quantitative real-time polymerase chain reaction.

Purpose

The purpose of this study is to elucidate the potential mechanism of rhubarb by suppressing extracellular signal-regulated kinase (ERK) to ameliorate brain edema. Materials and

Results

Rhubarb attenuated the brain edema after TBI, especially at the dose of 12 g/kg. Rhubarb significantly suppressed ERK, down-regulated MMP-9, and up-regulated ZO-1. Rhubarb might be a prospective therapeutic regimen to decrease edema in TBI. Conclusions: Rhubarb alleviates the edema by restraining the ERK signaling pathway. Our results contribute to the validation of the traditional use of rhubarb in the treatment of TBI and its mechanism. Summary: The aim of this study was to explore the potential mechanism of rhubarb by suppressing extracellular signal-regulated kinase to ameliorate brain edema. Results: Rhubarb ameliorates edema caused by traumatic brain injury by inhibiting the ERK/Matrix metalloproteinase 9/zonula occluden-1 signaling pathway. Abbreviations used: TBI: Traumatic brain injury, ERK: Extracellular signal-regulated kinase pathway, MMP-9: Matrix metalloproteinase 9, ZO-1: Zonula occluden-1, BBB: Blood-brain barrier, PCR: Polymerase chain reaction, TCM: Traditional Chinese medicine, MAPKs: Mitogen-activated protein kinases, CCI: Controlled cortical impact, DL: Rhubarb 3 g/kg in distilled water, DH: Rhubarb 12 g/kg in distilled water, EB: Evans blue, IOD: Integral optical density, MEK: Mitogen extracellular kinase, MMPs: Matrix metalloproteinases, NADPH: Nicotinamide adenine dinucleotide phosphate: ROS, reactive oxygen species.

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