Dl-3-n-butylphthalide Attenuates Acute Inflammatory Activation in Rats with Spinal Cord Injury by Inhibiting Microglial TLR4/NF-κB Signalling

Overview

Journal J Cell Mol Med

Specialties Cell Biology
Molecular Biology

Date 2017 Aug 27

PMID 28842949

Citations 25

Authors

Zili He

Yulong Zhou

Li Lin

Qingqing Wang

Sinan Khor

Yuqin Mao

Jiawei Li

Zengming Zhen

Jian Chen

Zhenzhen Gao

Fenzan Wu

Xie Zhang

Hongyu Zhang

Hua-Zi Xu

Zhouguang Wang

Jian Xiao

Affiliations

Soon will be listed here.

Abstract

In this study, we examined the neuroprotective effects and anti-inflammatory properties of Dl-3-n-butylphthalide (NBP) in Sprague-Dawley (SD) rats following traumatic spinal cord injury (SCI) as well as microglia activation and inflammatory response both in vivo and in vitro. Our results showed that NBP improved the locomotor recovery of SD rats after SCI an significantly diminished the lesion cavity area of the spinal cord, apoptotic activity in neurons, and the number of TUNEL-positive cells at 7 days post-injury. NBP inhibited activation of microglia, diminished the release of inflammatory mediators, and reduced the upregulation of microglial TLR4/NF-κB expression at 1 day post-injury. In a co-culture system with BV-2 cells and PC12 cells, NBP significantly reduced the cytotoxicity of BV-2 cells following lipopolysaccharide (LPS) stimulation. In addition, NBP reduced the activation of BV-2 cells, diminished the release of inflammatory mediators, and inhibited microglial TLR4/NF-κB expression in BV-2 cells. Our findings demonstrate that NBP may have neuroprotective and anti-inflammatory properties in the treatment of SCI by inhibiting the activation of microglia via TLR4/NF-κB signalling.

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References

David S, Zarruk J, Ghasemlou N . Inflammatory pathways in spinal cord injury. Int Rev Neurobiol. 2012; 106:127-52. DOI: 10.1016/B978-0-12-407178-0.00006-5. View

Feng Z, Riopel M, Li J, Donnelly L, Wang R . Downregulation of Fas activity rescues early onset of diabetes in c-Kit(Wv/+) mice. Am J Physiol Endocrinol Metab. 2012; 304(6):E557-65. DOI: 10.1152/ajpendo.00453.2012. View

Xu H, Feng Y . Effects of 3-n-butylphthalide on production of vasoactive substances by cerebral and aortic endothelial cells. Zhongguo Yao Li Xue Bao. 2001; 20(10):929-33. View

Impellizzeri D, Ahmad A, Di Paola R, Campolo M, Navarra M, Esposito E . Role of Toll like receptor 4 signaling pathway in the secondary damage induced by experimental spinal cord injury. Immunobiology. 2015; 220(9):1039-49. DOI: 10.1016/j.imbio.2015.05.013. View

Yang L, Li J, Xu S, Cai J, Lei H, Liu D . L-3-n-butylphthalide Promotes Neurogenesis and Neuroplasticity in Cerebral Ischemic Rats. CNS Neurosci Ther. 2015; 21(9):733-41. PMC: 6493029. DOI: 10.1111/cns.12438. View

Schwab J, Brechtel K, Mueller C, Failli V, Kaps H, Tuli S . Experimental strategies to promote spinal cord regeneration--an integrative perspective. Prog Neurobiol. 2006; 78(2):91-116. DOI: 10.1016/j.pneurobio.2005.12.004. View

Qian N, Liao Y, Feng Q, Tang Y, Dou K, Tao K . Spinal toll like receptor 3 is involved in chronic pancreatitis-induced mechanical allodynia of rat. Mol Pain. 2011; 7:15. PMC: 3048572. DOI: 10.1186/1744-8069-7-15. View

Jiang Y, Sun L, Xuan X, Wang J . Impacts of N-Butylphthalide on expression of growth factors in rats with focal cerebral ischemia. Bosn J Basic Med Sci. 2016; 16(2):102-7. PMC: 4852990. DOI: 10.17305/bjbms.2016.560. View

Penas C, Guzman M, Verdu E, Fores J, Navarro X, Casas C . Spinal cord injury induces endoplasmic reticulum stress with different cell-type dependent response. J Neurochem. 2007; 102(4):1242-55. DOI: 10.1111/j.1471-4159.2007.04671.x. View

10.

Feng X, Peng Y, Liu M, Cui L . DL-3-n-butylphthalide extends survival by attenuating glial activation in a mouse model of amyotrophic lateral sclerosis. Neuropharmacology. 2011; 62(2):1004-10. DOI: 10.1016/j.neuropharm.2011.10.009. View

11.

Allison D, Ditor D . Immune dysfunction and chronic inflammation following spinal cord injury. Spinal Cord. 2014; 53(1):14-8. DOI: 10.1038/sc.2014.184. View

12.

Choi J, Diao H, Feng Z, Lau A, Wang R, Jevnikar A . A fusion protein derived from plants holds promising potential as a new oral therapy for type 2 diabetes. Plant Biotechnol J. 2013; 12(4):425-35. DOI: 10.1111/pbi.12149. View

13.

Liu K, Huang J, Chen R, Zhang T, Shen L, Yang J . Protection against neurotoxicity by an autophagic mechanism. Braz J Med Biol Res. 2012; 45(5):401-7. PMC: 3854284. DOI: 10.1590/s0100-879x2012007500039. View

14.

Zhao C, Lei H, Zhang Y, Li L, Xu S, Cai J . L-3-n-Butylphthalide attenuates neuroinflammatory responses by downregulating JNK activation and upregulating Heme oxygenase-1 in lipopolysaccharide-treated mice. J Asian Nat Prod Res. 2015; 18(3):289-302. DOI: 10.1080/10286020.2015.1099524. View

15.

Li X, Lv H, Tan W, Fang B, Wang H, Ma H . Role of the TLR4 pathway in blood-spinal cord barrier dysfunction during the bimodal stage after ischemia/reperfusion injury in rats. J Neuroinflammation. 2014; 11:62. PMC: 3977699. DOI: 10.1186/1742-2094-11-62. View

16.

Carpentier P, Duncan D, Miller S . Glial toll-like receptor signaling in central nervous system infection and autoimmunity. Brain Behav Immun. 2007; 22(2):140-7. PMC: 2231624. DOI: 10.1016/j.bbi.2007.08.011. View

17.

Li J, Li Y, Ogle M, Zhou X, Song M, Song M . DL-3-n-butylphthalide prevents neuronal cell death after focal cerebral ischemia in mice via the JNK pathway. Brain Res. 2010; 1359:216-26. PMC: 3099257. DOI: 10.1016/j.brainres.2010.08.061. View

18.

Li J, Feng Z, Yeung F, Wong M, Oakie A, Fellows G . Aldehyde dehydrogenase 1 activity in the developing human pancreas modulates retinoic acid signalling in mediating islet differentiation and survival. Diabetologia. 2013; 57(4):754-64. DOI: 10.1007/s00125-013-3147-y. View

19.

Zhou K, Zhou Y, Wu K, Tian N, Wu Y, Wang Y . Stimulation of autophagy promotes functional recovery in diabetic rats with spinal cord injury. Sci Rep. 2015; 5:17130. PMC: 4657088. DOI: 10.1038/srep17130. View

20.

Casula M, Iyer A, Spliet W, Anink J, Steentjes K, Sta M . Toll-like receptor signaling in amyotrophic lateral sclerosis spinal cord tissue. Neuroscience. 2011; 179:233-43. DOI: 10.1016/j.neuroscience.2011.02.001. View