Xuefu Zhuyu decoction, a traditional Chinese medicine, provides neuroprotection in a rat model of traumatic brain injury via an anti-inflammatory pathway.

Zhihua Xing,Jiekun Luo,Chunhu Zhang,Chunyan Fu,Rong Fan,Jun Li,Wei Huang,Tao Tang,Yang Wang,Xingui Xiong,Weiping Liu,Zian Xia,Pingping Gan,Chenxia Sheng,Yong Zou,Weijun Peng

doi:10.1038/srep20040

Abstract

Neuroinflammation is central to the pathology of traumatic brain injury (TBI). Xuefu Zhuyu decoction (XFZY) is an effective traditional Chinese medicine to treat TBI. To elucidate its potential molecular mechanism, this study aimed to demonstrate that XFZY functions as an anti-inflammatory agent by inhibiting the PI3K-AKT-mTOR pathway. Sprague-Dawley rats were exposed to controlled cortical impact to produce a neuroinflammatory response. The treatment groups received XFZY (9 g/kg and 18 g/kg), Vehicle group and Sham group were gavaged with equal volumes of saline. The modified neurologic severity score (mNSS) and the Morris water maze test were used to assess neurological deficits. Arachidonic acid (AA) levels in brain tissue were measured using tandem gas chromatography-mass spectrometry. TNF-α and IL-1β levels in injured ipsilateral brain tissue were detected by ELISA. AKT and mTOR expression were measured by western blot analysis. The results indicated that XFZY significantly enhanced spatial memory acquisition. XFZY (especially at a dose of 9 g/kg) markedly reduced the mNSS and levels of AA, TNF-α and IL-1β. Significant downregulation of AKT/mTOR/p70S6K proteins in brain tissues was observed after the administration of XFZY (especially at a dose of 9 g/kg). XFZY may be a promising therapeutic strategy for reducing inflammation in TBI.

Highlights

Neuroinflammation is central to the pathology of traumatic brain injury (TBI)
(Fig. 2A) that was used in our study, Hydroxysafflor yellow A (HSYA) and Amygdalin originating from the monarch drug in prescription of Xuefu Zhuyu decoction (XFZY) were used as the central compounds
It was primarily found that the administration of XFZY after Traumatic brain injury (TBI) facilitated the recovery of neurological deficits and improved cognitive function

Summary

Introduction

Neuroinflammation is central to the pathology of traumatic brain injury (TBI). Significant downregulation of AKT/mTOR/ p70S6K proteins in brain tissues was observed after the administration of XFZY (especially at a dose of 9 g/kg). The first responders during inflammation are polymorphonuclear leukocytes (i.e., neutrophils), followed by monocytes, multipotent bone marrow-derived leukocytes that differentiate into macrophages[20]. These inflammatory cells that are recruited to the area of the lesion secrete several inflammatory factors[10,12]. Microglia/macrophages that are present in brain tissue after trauma are activated and persist as the M1 phenotype, which primarily produce pro-inflammatory cytokines (e.g., TNF-α and IL-1β ) during the chronic phase[10]. It is reasonable to consider AA, IL-1β and TNF-α as targets for assessing the degree of inflammation

Objectives

Methods

Results

Conclusion