Suppressive effects of Gua Lou Gui Zhi decoction on MCAO-induced NO and PGE2 production are dependent on the MAPK and NF-κB signaling pathways

Hu,Haixia; Zhu,Xiaoqin; Lin,Ruhui; Li,Zuanfang; Chen,Lidian

doi:10.3892/mmr.2016.5876

Suppressive effects of Gua Lou Gui Zhi decoction on MCAO-induced NO and PGE2 production are dependent on the MAPK and NF-κB signaling pathways

Authors:
- Haixia Hu
- Xiaoqin Zhu
- Ruhui Lin
- Zuanfang Li
- Lidian Chen
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Affiliations: Academy of Integrative Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350108, P.R. China, College of Rehabilitation Medicine, Fujian University of Traditional Chinese Medicine, Fuzhou, Fujian 350108, P.R. China
Published online on: October 21, 2016 https://doi.org/10.3892/mmr.2016.5876
Pages: 5141-5147
Copyright: © Hu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The present study aimed to investigate the inhibitory effects, and underlying mechanisms, of Gua Lou Gui Zhi decoction (GLGZD) in a rat model of neuroinflammation. Sprague-Dawley rats were treated with GLGZD following middle cerebral artery occlusion (MCAO). Neurological function and infarct volume were evaluated to confirm successful generation of the rat model. Subsequently, brain tissues and blood samples were collected for further analysis. Nitric oxide (NO) and prostaglandin E2 (PGE2) were evaluated in peripheral blood samples using the Griess reagent assay and an ELISA, respectively. The relative expression levels of inducible nitric oxide synthase (iNOS) and cylooxygenase‑2 (COX‑2) were detected by quantitative polymerase chain reaction and immunohistochemistry. The associated pathways, including nuclear factor‑κB (NF‑κB) and mitogen‑activated protein kinases (MAPK) signaling pathways, were detected by electrophoretic mobility shift assay and western blotting. The results demonstrated that treatment with GLGZD significantly inhibited MCAO-induced inflammation; GLGZD suppressed the production of NO and PGE2, and the expression of iNOS and COX‑2, by inhibiting NF‑κB activation and MAPK phosphorylation. These findings suggest that GLGZD, a potential agent for post‑stroke treatment, may exert anti‑inflammatory effects, thus providing neuroprotection.

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1	Brown GC and Neher JJ: Inflammatory neurodegeneration and mechanisms of microglial killing of neurons. Mol Neurobiol. 41:242–247. 2010. View Article : Google Scholar : PubMed/NCBI
2	Hu H, Li Z, Zhu X, Lin R, Lin J, Peng J, Tao J and Chen L: Gua Lou Gui Zhi decoction suppresses LPS-induced activation of the TLR4/NF-κB pathway in BV-2 murine microglial cells. Int J Mol Med. 31:1327–1332. 2013.PubMed/NCBI
3	Hu H, Li Z, Zhu X, Lin R, Peng J, Tao J and Chen L: GuaLou GuiZhi decoction inhibits LPS-induced microglial cell motility through the MAPK signaling pathway. Int J Mol Med. 32:1281–1286. 2013.PubMed/NCBI
4	Hu H, Lin R, Zhu X, Li Z and Chen L: Anti-inflammatory effects of Gualou Guizhi decoction in transient focal cerebral ischemic brains. Mol Med Rep. 12:1321–1327. 2015.PubMed/NCBI
5	Huang J, Tao J, Xue X, Yang S, Han P, Lin Z, Xu W, Lin J, Peng J and Chen L: Gua Lou Gui Zhi decoction exerts neuroprotective effects on post-stroke spasticity via the modulation of glutamate levels and AMPA receptor expression. Int J Mol Med. 31:841–848. 2013.PubMed/NCBI
6	Longa EZ, Weinstein PR, Carlson S and Cummins R: Reversible middle cerebral artery occlusion without craniectomy in rats. Stroke. 20:84–91. 1989. View Article : Google Scholar : PubMed/NCBI
7	Kovac A, Erickson MA and Banks WA: Brain microvascular pericytes are immunoactive in culture: Cytokine, chemokine, nitric oxide and LRP-1 expression in response to lipopolysaccharide. J Neuroinflammation. 8:1392011. View Article : Google Scholar : PubMed/NCBI
8	Livak KJ and Schmittgen TD: Analysis of relative gene expression data using real-time quantitative PCR and the 2(−Delta Delta C(T)) Method. Methods. 25:402–408. 2001. View Article : Google Scholar : PubMed/NCBI
9	Egger T, Schuligoi R, Wintersperger A, Amann R, Malle E and Sattler W: Vitamin E (alpha-tocopherol) attenuates cyclo-oxygenase 2 transcription and synthesis in immortalized murine BV-2 microglia. Biochem J. 370:459–467. 2003. View Article : Google Scholar : PubMed/NCBI
10	Glezer I, Simard AR and Rivest S: Neuroprotective role of the innate immune system by microglia. Neuroscience. 29:867–883. 2007. View Article : Google Scholar
11	Perry VH, Nicoll JA and Holmes C: Microglia in neurodegenerative disease. Nat Rev Neurol. 6:193–201. 2010. View Article : Google Scholar : PubMed/NCBI
12	Rock RB and Peterson PK: Microglia as a pharmacological target in infectious and inflammatory diseases of the brain. J Neuroimmune Pharmacol. 1:117–126. 2006. View Article : Google Scholar : PubMed/NCBI
13	Minghetti L: Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol. 63:901–910. 2004. View Article : Google Scholar : PubMed/NCBI
14	Griffiths MR, Gasque P and Neal JW: The multiple roles of the innate immune system in the regulation of apoptosis and inflammation in the brain. J Neuropathol Exp Neurol. 68:217–226. 2009. View Article : Google Scholar : PubMed/NCBI
15	Amor S, Puentes F, Baker D and van der Valk P: Inflammation in neurodegenerative diseases. Immunology. 129:154–169. 2010. View Article : Google Scholar : PubMed/NCBI
16	Lo JY, Kamarudin MN, Hamdi OA, Awang K and Kadir HA: Curcumenol isolated from Curcuma zedoaria suppresses Akt-mediated NF-κB activation and p38 MAPK signaling pathway in LPS-stimulated BV-2 microglial cells. Food Funct. 6:3550–3559. 2015. View Article : Google Scholar : PubMed/NCBI
17	Banati RB, Gehrmann J, Schubert P and Kreutzberg GW: Cytotoxicity of microglia. Glia. 7:111–118. 1993. View Article : Google Scholar : PubMed/NCBI
18	Rock RB and Peterson PK: Microglia as a pharmacological target in infectious and inflammatory diseases of the brain. J Neuroimmune Pharmacol. 1:117–126. 2006. View Article : Google Scholar : PubMed/NCBI
19	Abramson SB, Amin AR, Clancy RM and Attur M: The role of nitric oxide in tissue destruction. Best Pract Res Clin Rheumatol. 15:831–845. 2001. View Article : Google Scholar : PubMed/NCBI
20	Boje KM: Nitric oxide neurotoxicity in neurodegenerative diseases. Front Biosci. 9:763–776. 2004. View Article : Google Scholar : PubMed/NCBI
21	Minghetti L: Cyclooxygenase-2 (COX-2) in inflammatory and degenerative brain diseases. J Neuropathol Exp Neurol. 63:901–910. 2004. View Article : Google Scholar : PubMed/NCBI
22	Harari OA and Liao JK: NF-kB and innate immunity in ischemic stroke. Ann N Y Acad Sci. 1207:32–40. 2010. View Article : Google Scholar : PubMed/NCBI
23	Baldwin AS Jr: The NF-kappa B and I kappa B proteins: New discoveries and insights. Annu Rev Immunol. 14:649–683. 1996. View Article : Google Scholar : PubMed/NCBI
24	Lee AK, Sung SH, Kim YC and Kim SG: Inhibition of lipopolysaccharide-inducible nitric oxide synthase, TNF-alpha and COX-2 expression by sauchinone effects on I-kappaBalpha phosphorylation, C/EBP and AP-1 activation. Br J Pharmacol. 139:11–20. 2003. View Article : Google Scholar : PubMed/NCBI
25	Baeuerle PA and Henkel T: Function and activation of NF-kappa B in the immune system. Annu Rev Immunol. 12:141–179. 1994. View Article : Google Scholar : PubMed/NCBI
26	Kim YJ, Hwang SY, Oh ES, Oh S and Han IO: IL-1beta, an immediate early protein secreted by activated microglia, induces iNOS/NO in C6 astrocytoma cells through p38 MAPK and NF-kappaB pathways. J Neurosci Res. 84:1037–1046. 2006. View Article : Google Scholar : PubMed/NCBI
27	Zhang L and Ai H: Effects of Gua Lou Gui Zhi decoction on c-fos and c-jun on epileptic Rats. Sichuan Journal of Traditional Chinese Medicine. 23:21–22. 2005.
28	Yang C, Chen L and Tao J: New usage of a classical formula-Gua Lou Gui Zhi Decoction. Liaoning Journal of Traditional Chinese Medicine. 8:166–167. 2012.