XingNaoJing, prescription of traditional Chinese medicine, prevents autophagy in experimental stroke by repressing p53-DRAM pathway

BMC Complementary and Alternative Medicine

DongFeng Chen²  GuiHua Huang¹  JianHong Zhou⁴  YingTao Lai⁴  RuDong Deng⁴  YiWei Li⁴  FeiJian Zeng¹  Fei Li⁴  YueChun Huang³  Gang Wei³ 

[1] The first affiliated hospital of GuangXi university of Chinese medicine, Dongge Road No. 89-9, Nanning 530023, China;Department of Anatomy, Guangzhou university of Chinese medicine, Jichang Road No.12, Guangzhou 510405, China;Research & Development of New Drugs, Guangzhou University of Chinese Medicine, Guangzhou 510006, China;Molecular medicine, Guangzhou University of Chinese Medicine, Guangzhou 510006, China

关键词: Stroke;    Damage-regulated autophagy modulator;    p53;    Autophagy;    Xingnaojing;   

Others  :  1233222
DOI  :  10.1186/s12906-015-0882-2

 received in 2015-01-19, accepted in 2015-09-28,  发布年份 2015

【 摘 要 】

Background

Xingnaojing (XNJ), a well known prescription in traditional Chinese medicine, has been used for treatment of stroke in China. However, the effects and mechanisms of XNJ on autophagy are not clear. Here, we used the cell models of autophagy induced by serum-free condition and ischemia stroke in rats to further investigate whether the p53-DRAM pathway is involved in the effects of XNJ on autophagy.

Methods

We used the cell model of autophagy induced by serum-free condition and the rat model of ischemia caused by a middle cerebral artery occlusion (MCAO). The effects of XNJ on p53 transcriptional activity of PC12 cells were evaluated by the luciferase activity assay. The mRNA levels and the expression of p53 and its target autophagy gene DRAM (damage-regulated autophagy modulator) were analyzed respectively by Quantitative-RTPCR and Western blot assay. The activation of autophagy was detected by the levels of autophagy markers, microtubule associated protein light chain 3 (LC3) and p62 by Immunofluorescence and Western blot. p53 inhibitor was used to determine whether p53 is responsible for the effects of XNJ on preventing autophagy.

Results

The assay for luciferase activity of p53 promoter indicated that XNJ inhibited p53 transcriptional activity. XNJ reduced the expression of p53 and its target autophagy gene DRAM (damage-regulated autophagy modulator) in serum-free condition PC12 cells and the cortex in MCAO rats. XNJ reduced autophagy of PC12 cells induced by serum-free condition and the cortex in MCAO rats. Furthermore, suppression of p53 by p53 inhibitor significantly reduced the effects of XNJ on the autophagy of PC12 cells in serum-free condition.

Conclusion

XNJ prevents autophagy in experimental stroke by repressing p53/DRAM pathway. Our findings are therefore of considerable therapeutic significance and provide the novel and potential application of XNJ for the treatment of brain diseases.

【 授权许可】

   
2015 Wei et al.

【 图 表 】

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