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

Abstract

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

Specific role of the tight junction proteins occludin and claudin-5 on the blood–brain barrier during Listeria monocytogenes infection

“…Immunohistochemistry. Immunohistochemistry assay was done according to Yang, et al (26). Briefly, eight-weekold BALB/c mice were randomly divided into 2 groups, with 27 mice in the test group and 3 mice in the control group.…”

Neuroprotective Effects of Anthraquinones from Rhubarb in Central Nervous System Diseases

“…On the other hand, Yang Wang and his colleagues [50–52] reported that rhubarb and rhein exhibited protective effects after TBI through inhibiting extracellular regulated kinase (ERK)/matrix metalloproteinase-9 (MMP-9) pathway and reducing oxidative stress; besides, they could reduce brain edema and BBB permeability through inhibiting ERK/MMP-9 pathway by preventing activation of gp91phox subunit of NADPH oxidase induced ROS production in vitro and in vivo [50]. Similarly, another study suggested that oral administration of rhubarb downregulated MMP-9 and upregulated ZO-1 by inhibiting ERK signaling pathway [51]. What is more, rhubarb and rhein also improved the activities of SOD and CAT, increased the level of glutathione (GSH) and the ratio of GSH/glutathione disulfide (GSSG) and decreased the levels of MDA and GSSG in TBI rats [52].…”