Gualou Guizhi Granule Protects Against Oxidative Injury by Activating Nrf2/ARE Pathway in Rats and PC12 Cells
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Stroke involves numerous pathophysiological processes and oxidative stress is considered as a main cellular event in its pathogenesis. The nuclear factor erythroid-2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway plays a key role in inducing phase II detoxifying enzymes and antioxidant proteins and is now considered as a interesting therapeutic target for the treatment of stroke. The objective of this study is to investigate the protective effect of Gualou Guizhi granule (GLGZG) against oxidative stress and explore the protective mechanism of the Nrf2/ARE pathway. In vivo, administration of GLGZG in a rat model of focal cerebral ischemia significantly suppressed oxidative injury by increasing the activity of superoxide dismutase and glutathione level and decreasing reactive oxygen species and malondialdehyde levels. Western blot analysis showed that GLGZG induced nuclear translocation of Nrf2, and combined with real-time PCR results, which indicated that GLGZG up-regulated the Nrf2/ARE pathway. In addition, in cultured PC12 cells, GLGZG protected against H2O2 induced oxidative injury and activated the Nrf2/ARE pathway. All the results demonstrated that GLGZG in the management of cerebral ischemia and H2O2 induced oxidative injury may be associated with activation of Nrf2/ARE signaling pathway.
KeywordsGualou Guizhi granule Cerebral ischemia Oxidative stress Nrf2
This research was done in Collaborative Innovation Center for Rehabilitation Technology and TCM Rehabilitation Research Center of SATCM and was funded by the National Natural Science Foundation of China (No. 81674046) and Fujian Provincial Health and Family Planning Commission Youth Talent Project (2017-1-71).
Compliance with Ethical Standards
Conflict of interest
All the authors declare no conflict of interest.
- 5.Sun X (2010) Research on formula treating paralysis and spasticity from ‘treatis-eon febrile and miscellaneous diseases’. Zhongguo Zhong Yi Ji Chu Yi Xue Za Zhi 8:644–645Google Scholar
- 6.Zhang L, Ai H (2005) Effects of Gua Lou Gui Zhi decoction on c-fos and c-ju-n in epileptic rats. Sichuan Hua xi Zhong Yi Yao Yan Jiu Suo 23:21–22Google Scholar
- 7.Yang C, Chen L, Tao J (2010) New usage of a classical formula-Gua Lou Gui Zhi decoction. Liaoning Zhong Yi Za Zhi 8:166–167Google Scholar
- 8.Xu W, Huang MQ, Li H, Chen X, Zhang YQ, Liu J, Xu W, Chu KD, Chen LD (2015) Chemical profiling and quantification of Gua-Lou-Gui-Zhi decoction by high performance liquid chromatography/quadrupole-time-of-flight mass spectrometry and ultra-performance liquid chromatography/triple quadrupole mass spectrometry. J Chromatogr B 986–987:69–84CrossRefGoogle Scholar
- 10.Chen XW, Li H, Chen LD, Xu W, Chu KD, Que JH, Fang YH (2014) Simultaneous determination of six active ingredients in Gualou Guizhi decoction by HPLC. J Fujian Univ Tradit Chin Med 24:31–34Google Scholar
- 13.Zhang YQ, Zhang S, Li H, Huang MQ, Xu W, Chu KD, Chen LD, Chen X (2015) Ameliorative effects of Gualou Guizhi decoction on inflammation in focal cerebral ischemic-reperfusion injury. Mol Med Rep 129:88–99Google Scholar
- 15.Zhang Y-q, Li H, Xu W, Xu W, Huang M, Chu K-d, Chen L-d (2015) Effects of Gualou Guizhi granule on blood brain barrier permeability and neuroprotection in cerebral ischemia-reperfusion injury rat. China J Tradit Chin Med Pharm 30:40–47Google Scholar
- 16.Lin Y, Xu W, Zhang YQ, Li H, Xu W (2015) Anti-apoptosis effects of Gualou Guizhi granule on stroke rats and hippocampal neuron. Rehab Med 25:38–43Google Scholar
- 17.Zhang Y-q, Sun C-t, Li H, Xu W, Chu K-d, Lin Y (2017) Effects of Gualou Guizhi granules on excitatory toxic damage of PC12 induced by glutamate. Chin J Inform TCM 24:39–43Google Scholar
- 24.Wang AL, Niu Q, Shi N et al (2015) Glutamine ameliorates intestinal ischemia-reperfusion injury in rats by activating the Nrf2/Are signaling pathway. Int J Clin Exp Pathol l8:7896–7904Google Scholar
- 27.Chen W, Wang H, Zhang SW (2011) Effect of trichosanthin on high plasma Ho-mocystein in rats with cerebral ischemia-reperfusion. JETCM 20:275–277Google Scholar
- 28.Chen W, Zhang SW, Wang H (2011) Study of radices trichosanthis on neuronal apoptosisin rats with local cerebral ischemia reperfusion. Mod J Integr Trad Chin West Med 20:1844–1845Google Scholar
- 30.Liu SL, Liu ZW, Lu PQ, Zhang Y, Zhang JD, Jia DH, Yao YO, Cao ZB (2010) Protective effects of catechin on cerebral ischemia–reperfusion injury in rats and its mechanism. Chin Pharmacol Bull 26:255–257Google Scholar
- 31.Lei JR, Qin J, Zhang J, Huang KM, Fu R, Zhou ZM (2010) Effects of curcumin on inflammatory reaction and blood-brain barrier permeability in rats following cerebral ischemic injury. Chin Pharmacol Bull 26:120–123Google Scholar
- 32.Jiang Q, Xia B (2007) The anti-inflammatory effect of 6-gingerol on focal ischemia-reperfusion injury in rats. J Xiangning Coll (Med Sci) 21:281–283Google Scholar