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CNS & Neurological Disorders - Drug Targets

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ISSN (Print): 1871-5273
ISSN (Online): 1996-3181

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Review Article

A Pivotal Role of the Nrf2 Signaling Pathway in Spinal Cord Injury: A Prospective Therapeutics Study

Author(s): Saeed Samarghandian, Ali Mohammad Pourbagher-Shahri, Milad Ashrafizadeh, Haroon Khan, Fatemeh Forouzanfar, Hamed Aramjoo and Tahereh Farkhondeh*

Volume 19, Issue 3, 2020

Page: [207 - 219] Pages: 13

DOI: 10.2174/1871527319666200604175118

Price: $65

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Abstract

The nuclear erythroid 2-related factor 2 (Nrf2) signaling pathway has a main role against oxidative stress and inflammation. Spinal Cord Injury (SCI) leads to the high secretion of inflammatory cytokines and reactive oxygen species, which disturbs nervous system function and regeneration. Several studies have indicated that the activation of the Nrf2 signaling pathway may be effective against inflammation after SCI. The experimental studies have indicated that many chemical and natural agents act as Nrf2 inducer, which inhibits the SCI progression. Thus, the finding of novel Nrf2- inducer anti-inflammatory agents may be a valuable approach in drug discovery. In the present review, we discussed the Nrf2 signal pathway and crosstalk with the NF-κB pathway and also the impact of this pathway on inflammation in animal models of SCI. Furthermore, we discussed the regulation of Nrf2 by several phytochemicals and drugs, as well as their effects on the SCI inhibition. Therefore, the current study presented a new hypothesis of the development of anti-inflammatory agents that mediate the Nrf2 signaling pathway for treating the SCI outcomes.

Keywords: Inflammation, nervous system, Nrf2, oxidative stress, spinal cord injury, NQO-1.

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[1]
Kang Y, et al. Epidemiology of worldwide spinal cord injury: a literature review. J Neurorestoratol 2017; 6: 1-9.
[http://dx.doi.org/10.2147/JN.S143236]
[2]
Norenberg MD, Smith J, Marcillo A. The pathology of human spinal cord injury: defining the problems. Mary Ann Liebert, Inc. 2004.
[3]
Russo MV, McGavern DB. Inflammatory neuroprotection following traumatic brain injury. Science 2016; 353(6301): 783-5.
[http://dx.doi.org/10.1126/science.aaf6260] [PMID: 27540166]
[4]
Ransohoff RM. How neuroinflammation contributes to neurodegeneration. Science 2016; 353(6301): 777-83.
[http://dx.doi.org/10.1126/science.aag2590] [PMID: 27540165]
[5]
Mortazavi MM, Verma K, Harmon OA, et al. The microanatomy of spinal cord injury: a review. Clin Anat 2015; 28(1): 27-36.
[http://dx.doi.org/10.1002/ca.22432] [PMID: 25044123]
[6]
Yang L, Blumbergs PC, Jones NR, Manavis J, Sarvestani GT, Ghabriel MN. Early expression and cellular localization of proinflammatory cytokines interleukin-1β, interleukin-6, and tumor necrosis factor-α in human traumatic spinal cord injury. Spine 2004; 29(9): 966-71.
[http://dx.doi.org/10.1097/00007632-200405010-00004] [PMID: 15105666]
[7]
Streit WJ, Semple-Rowland SL, Hurley SD, Miller RC, Popovich PG, Stokes BT. Cytokine mRNA profiles in contused spinal cord and axotomized facial nucleus suggest a beneficial role for inflammation and gliosis. Exp Neurol 1998; 152(1): 74-87.
[http://dx.doi.org/10.1006/exnr.1998.6835] [PMID: 9682014]
[8]
Pan JZ, Ni L, Sodhi A, Aguanno A, Young W, Hart RP. Cytokine activity contributes to induction of inflammatory cytokine mRNAs in spinal cord following contusion. J Neurosci Res 2002; 68(3): 315-22.
[http://dx.doi.org/10.1002/jnr.10215] [PMID: 12111861]
[9]
Rice T, Larsen J, Rivest S, Yong VW. Characterization of the early neuroinflammation after spinal cord injury in mice. J Neuropathol Exp Neurol 2007; 66(3): 184-95.
[http://dx.doi.org/10.1097/01.jnen.0000248552.07338.7f] [PMID: 17356380]
[10]
Taoka Y, Okajima K, Uchiba M, et al. Role of neutrophils in spinal cord injury in the rat. Neuroscience 1997; 79(4): 1177-82.
[http://dx.doi.org/10.1016/S0306-4522(97)00011-0] [PMID: 9219976]
[11]
Stirling DP, Yong VW. Dynamics of the inflammatory response after murine spinal cord injury revealed by flow cytometry. J Neurosci Res 2008; 86(9): 1944-58.
[http://dx.doi.org/10.1002/jnr.21659] [PMID: 18438914]
[12]
Samarghandian S, Azimi-Nezhad M, Shabestari MM, Azad FJ, Farkhondeh T, Bafandeh F. Effect of chronic exposure to cadmium on serum lipid, lipoprotein and oxidative stress indices in male rats. Interdiscip Toxicol 2015; 8(3): 151-4.
[http://dx.doi.org/10.1515/intox-2015-0023] [PMID: 27486375]
[13]
Banati RB, Gehrmann J, Schubert P, Kreutzberg GW. Cytotoxicity of microglia. Glia 1993; 7(1): 111-8.
[http://dx.doi.org/10.1002/glia.440070117] [PMID: 8423058]
[14]
Whetstone WD, Hsu JY, Eisenberg M, Werb Z, Noble-Haeusslein LJ. Blood-spinal cord barrier after spinal cord injury: relation to revascularization and wound healing. J Neurosci Res 2003; 74(2): 227-39.
[http://dx.doi.org/10.1002/jnr.10759] [PMID: 14515352]
[15]
Noble LJ, Wrathall JR. Distribution and time course of protein extravasation in the rat spinal cord after contusive injury. Brain Res 1989; 482(1): 57-66.
[http://dx.doi.org/10.1016/0006-8993(89)90542-8] [PMID: 2706482]
[16]
Schwab ME, Caroni P. Oligodendrocytes and CNS myelin are nonpermissive substrates for neurite growth and fibroblast spreading in vitro. J Neurosci 1988; 8(7): 2381-93.
[http://dx.doi.org/10.1523/JNEUROSCI.08-07-02381.1988] [PMID: 3074158]
[17]
David S, Bouchard C, Tsatas O, Giftochristos N. Macrophages can modify the nonpermissive nature of the adult mammalian central nervous system. Neuron 1990; 5(4): 463-9.
[http://dx.doi.org/10.1016/0896-6273(90)90085-T] [PMID: 2206534]
[18]
Kawaja MD, Gage FH. Reactive astrocytes are substrates for the growth of adult CNS axons in the presence of elevated levels of nerve growth factor. Neuron 1991; 7(6): 1019-30.
[http://dx.doi.org/10.1016/0896-6273(91)90346-2] [PMID: 1684900]
[19]
Hsu CY, Halushka PV, Hogan EL, Banik NL, Lee WA, Perot PL Jr. Alteration of thromboxane and prostacyclin levels in experimental spinal cord injury. Neurology 1985; 35(7): 1003-9.
[http://dx.doi.org/10.1212/WNL.35.7.1003] [PMID: 3892363]
[20]
Tymianski M, Tator CH. Normal and abnormal calcium homeostasis in neurons: a basis for the pathophysiology of traumatic and ischemic central nervous system injury. Neurosurgery 1996; 38(6): 1176-95.
[PMID: 8727150]
[21]
Zerangue N, Arriza JL, Amara SG, Kavanaugh MP. Differential modulation of human glutamate transporter subtypes by arachidonic acid. J Biol Chem 1995; 270(12): 6433-5.
[http://dx.doi.org/10.1074/jbc.270.12.6433] [PMID: 7896776]
[22]
Pitt D, Nagelmeier IE, Wilson HC, Raine CS. Glutamate uptake by oligodendrocytes: implications for excitotoxicity in multiple sclerosis. Neurology 2003; 61(8): 1113-20.
[http://dx.doi.org/10.1212/01.WNL.0000090564.88719.37] [PMID: 14581674]
[23]
Takahashi JL, Giuliani F, Power C, Imai Y, Yong VW. Interleukin-1β promotes oligodendrocyte death through glutamate excitotoxicity. Ann Neurol 2003; 53(5): 588-95.
[http://dx.doi.org/10.1002/ana.10519] [PMID: 12730992]
[24]
Piani D, Frei K, Pfister HW, Fontana A. Glutamate uptake by astrocytes is inhibited by reactive oxygen intermediates but not by other macrophage-derived molecules including cytokines, leukotrienes or platelet-activating factor. J Neuroimmunol 1993; 48(1): 99-104.
[http://dx.doi.org/10.1016/0165-5728(93)90063-5] [PMID: 7901235]
[25]
Samarghandian S, Azimi-Nezhad M and, Farkhondeh T. Catechin treatment ameliorates diabetes and its complications in streptozotocin-induced diabetic rats. Dose Response 2017; 15(1): 1559325817691158.
[http://dx.doi.org/10.1177/1559325817691158] [PMID: 28228702]
[26]
Kinuta Y, Kimura M, Itokawa Y, Ishikawa M, Kikuchi H. Changes in xanthine oxidase in ischemic rat brain. J Neurosurg 1989; 71(3): 417-20.
[http://dx.doi.org/10.3171/jns.1989.71.3.0417] [PMID: 2549224]
[27]
Farkhondeh T, Samarghandian S. Antidotal effects of curcumin against agents-induced cardiovascular toxicity. Cardiovasc Hematol Disord Drug Targets 2016; 16(1): 30-7.
[28]
Popovich PG, Wei P, Stokes BT. Cellular inflammatory response after spinal cord injury in Sprague-Dawley and Lewis rats. J Comp Neurol 1997; 377(3): 443-64.
[http://dx.doi.org/10.1002/(SICI)1096-9861(19970120)377:3<443::AID-CNE10>3.0.CO;2-S] [PMID: 8989657]
[29]
Kil K, Zang YC, Yang D, et al. T cell responses to myelin basic protein in patients with spinal cord injury and multiple sclerosis. J Neuroimmunol 1999; 98(2): 201-7.
[http://dx.doi.org/10.1016/S0165-5728(99)00057-0] [PMID: 10430053]
[30]
Shechter R, London A, Varol C, et al. Infiltrating blood-derived macrophages are vital cells playing an anti-inflammatory role in recovery from spinal cord injury in mice. PLoS Med 2009; 6(7): e1000113.
[http://dx.doi.org/10.1371/journal.pmed.1000113] [PMID: 19636355]
[31]
Schwartz M, Yoles E. Immune-based therapy for spinal cord repair: autologous macrophages and beyond. J Neurotrauma 2006; 23(3-4): 360-70.
[http://dx.doi.org/10.1089/neu.2006.23.360] [PMID: 16629622]
[32]
Bomstein Y, Marder JB, Vitner K, et al. Features of skin coincubated macrophages that promote recovery from spinal cord injury. J Neuroimmunol 2003; 142(1-2): 10-6.
[http://dx.doi.org/10.1016/S0165-5728(03)00260-1] [PMID: 14512160]
[33]
Kigerl KA, Gensel JC, Ankeny DP, Alexander JK, Donnelly DJ, Popovich PG. Identification of two distinct macrophage subsets with divergent effects causing either neurotoxicity or regeneration in the injured mouse spinal cord. J Neurosci 2009; 29(43): 13435-44.
[http://dx.doi.org/10.1523/JNEUROSCI.3257-09.2009] [PMID: 19864556]
[34]
Samarghandian S, Azimi-Nezhad M, Borji A, et al. Inhibitory and cytotoxic activities of chrysin on human breast adenocarcinoma cells by induction of apoptosis. Pharmacogn Mag 2016; 12(Suppl. 4): S436-40.
[http://dx.doi.org/10.4103/0973-1296.191453] [PMID: 27761071]
[35]
Samarghandian S, Azimi-Nezhad M, Farkhondeh T. Immunomodulatory and antioxidant effects of saffron aqueous extract (Crocus sativus L.) on streptozotocin-induced diabetes in rats. Indian Heart J 2017; 69(2): 151-9.
[http://dx.doi.org/10.1016/j.ihj.2016.09.008] [PMID: 28460761]
[36]
Kotlo KU, Yehiely F, Efimova E, et al. Nrf2 is an inhibitor of the Fas pathway as identified by Achilles’ Heel Method, a new function-based approach to gene identification in human cells. Oncogene 2003; 22(6): 797-806.
[http://dx.doi.org/10.1038/sj.onc.1206077] [PMID: 12584558]
[37]
Shao Z, Lv G, Wen P, et al. Silencing of PHLPP1 promotes neuronal apoptosis and inhibits functional recovery after spinal cord injury in mice. Life Sci 2018; 209: 291-9.
[http://dx.doi.org/10.1016/j.lfs.2018.08.030] [PMID: 30114409]
[38]
Arts RJ, Joosten LA, Dinarello CA, Kullberg BJ, van der Meer JW, Netea MG. TREM-1 interaction with the LPS/TLR4 receptor complex. Eur Cytokine Netw 2011; 22(1): 11-4.
[http://dx.doi.org/10.1684/ecn.2011.0274] [PMID: 21393102]
[39]
Ubagai T, Nakano R, Kikuchi H, Ono Y. Gene expression analysis of TREM1 and GRK2 in polymorphonuclear leukocytes as the surrogate biomarkers of acute bacterial infections. Int J Med Sci 2014; 11(2): 215-21.
[http://dx.doi.org/10.7150/ijms.7231] [PMID: 24465168]
[40]
Li Z, Wu F, Xu D, Zhi Z, Xu G. Inhibition of TREM1 reduces inflammation and oxidative stress after spinal cord injury (SCI) associated with HO-1 expressions. Biomed Pharmacother 2019; 109: 2014-21.
[http://dx.doi.org/10.1016/j.biopha.2018.08.159] [PMID: 30551457]
[41]
Mao L, Wang HD, Wang XL, Tian L, Xu JY. Disruption of Nrf2 exacerbated the damage after spinal cord injury in mice. J Trauma Acute Care Surg 2012; 72(1): 189-98.
[http://dx.doi.org/10.1097/TA.0b013e31821bf541] [PMID: 21926641]
[42]
Mao L, Wang H, Wang X, Liao H, Zhao X. Transcription factor Nrf2 protects the spinal cord from inflammation produced by spinal cord injury. J Surg Res 2011; 170(1): e105-15.
[http://dx.doi.org/10.1016/j.jss.2011.05.049] [PMID: 21764072]
[43]
Li W-C, Jiang DM, Hu N, Qi XT, Qiao B, Luo XJ. Lipopolysaccharide preconditioning attenuates neuroapoptosis and improves functional recovery through activation of Nrf2 in traumatic spinal cord injury rats. Int J Neurosci 2013; 123(4): 240-7.
[http://dx.doi.org/10.3109/00207454.2012.755181] [PMID: 23215850]
[44]
Li W, Jiang D, Li Q, et al. Lipopolysaccharide-induced preconditioning protects against traumatic spinal cord injury by upregulating Nrf2 expression in rats. Life Sci 2016; 162: 14-20.
[http://dx.doi.org/10.1016/j.lfs.2016.08.008] [PMID: 27515502]
[45]
Zhu Q, et al. Low-dose lipopolysaccharide mediated up-regulation of Nrf2 attenuates inflammatory response in rats with spinal cord njury Xi bao yu fen zi mian yi xue za zhi= Chinese journal of cellular and molecular immunology 2015; 31(4): 437-2.
[46]
Mao L, et al. Disruption of Nrf2 enhances the upregulation of nuclear factor-kappaB activity, tumor necrosis factor-α, and matrix metalloproteinase-9 after spinal cord injury in mice. Mediators Inflamm 2010; 2010: 238321.
[47]
Guo Y, Liu Y, Xu L, Wu D, Wu H, Li CY. Reduced Nrf2 and Phase II enzymes expression in immune-mediated spinal cord motor neuron injury. Neurol Res 2010; 32(5): 460-5.
[http://dx.doi.org/10.1179/174313209X385563] [PMID: 19589199]
[48]
Xu J, Huang G, Zhang K, et al. Nrf2 activation in astrocytes contributes to spinal cord ischemic tolerance induced by hyperbaric oxygen preconditioning. J Neurotrauma 2014; 31(15): 1343-53.
[http://dx.doi.org/10.1089/neu.2013.3222] [PMID: 24716787]
[49]
Li Q, Li J, Zhang L, Wang B, Xiong L. Preconditioning with hyperbaric oxygen induces tolerance against oxidative injury via increased expression of heme oxygenase-1 in primary cultured spinal cord neurons. Life Sci 2007; 80(12): 1087-93.
[http://dx.doi.org/10.1016/j.lfs.2006.11.043] [PMID: 17291539]
[50]
Nie H, Xiong L, Lao N, Chen S, Xu N, Zhu Z. Hyperbaric oxygen preconditioning induces tolerance against spinal cord ischemia by upregulation of antioxidant enzymes in rabbits. J Cereb Blood Flow Metab 2006; 26(5): 666-74.
[http://dx.doi.org/10.1038/sj.jcbfm.9600221] [PMID: 16136055]
[51]
Pomeshchik Y, et al. Does Nrf2 gene transfer facilitate recovery after contusion spinal cord injury? Antioxid Redox Signal 2014; 20(8): 1313-23.
[http://dx.doi.org/10.1089/ars.2013.5453]]
[52]
Srinivas G, Babykutty S, Sathiadevan PP, Srinivas P. Molecular mechanism of emodin action: transition from laxative ingredient to an antitumor agent. Med Res Rev 2007; 27(5): 591-608.
[http://dx.doi.org/10.1002/med.20095] [PMID: 17019678]
[53]
Alisi A, Pastore A, Ceccarelli S, et al. Emodin prevents intrahepatic fat accumulation, inflammation and redox status imbalance during diet-induced hepatosteatosis in rats. Int J Mol Sci 2012; 13(2): 2276-89.
[http://dx.doi.org/10.3390/ijms13022276] [PMID: 22408453]
[54]
Zeng HH, Huang YR, Li ZJ, Wang Y, Zhang S. Effects of emodin on oxidative stress and inflammatory response in rats with acute spinal cord injury. Zhongguo Zhongyao Zazhi 2018; 43(9): 1886-93.
[PMID: 29902901]
[55]
Park S, Kim DS, Kang S. Gastrodia elata Blume water extracts improve insulin resistance by decreasing body fat in diet-induced obese rats: vanillin and 4-hydroxybenzaldehyde are the bioactive candidates. Eur J Nutr 2011; 50(2): 107-18.
[http://dx.doi.org/10.1007/s00394-010-0120-0] [PMID: 20577883]
[56]
Dai J-N, Zong Y, Zhong LM, et al. Gastrodin inhibits expression of inducible NO synthase, cyclooxygenase-2 and proinflammatory cytokines in cultured LPS-stimulated microglia via MAPK pathways. PLoS One 2011; 6(7): e21891.
[http://dx.doi.org/10.1371/journal.pone.0021891] [PMID: 21765922]
[57]
Song C, Fang S, Lv G, Mei X. Gastrodin promotes the secretion of brain-derived neurotrophic factor in the injured spinal cord. Neural Regen Res 2013; 8(15): 1383-9.
[PMID: 25206433]
[58]
Du F, Wang X, Shang B, et al. Gastrodin ameliorates spinal cord injury via antioxidant and anti-inflammatory effects. Acta Biochim Pol 2016; 63(3): 589-93.
[http://dx.doi.org/10.18388/abp.2016_1272] [PMID: 27474401]
[59]
Farombi EO, Shrotriya S, Na HK, Kim SH, Surh YJ. Curcumin attenuates dimethylnitrosamine-induced liver injury in rats through Nrf2-mediated induction of heme oxygenase-1. Food Chem Toxicol 2008; 46(4): 1279-87.
[http://dx.doi.org/10.1016/j.fct.2007.09.095] [PMID: 18006204]
[60]
Yang C, Zhang X, Fan H, Liu Y. Curcumin upregulates transcription factor Nrf2, HO-1 expression and protects rat brains against focal ischemia. Brain Res 2009; 1282: 133-41.
[http://dx.doi.org/10.1016/j.brainres.2009.05.009] [PMID: 19445907]
[61]
Jin W, Wang J, Zhu T, et al. Anti-inflammatory effects of curcumin in experimental spinal cord injury in rats. Inflamm Res 2014; 63(5): 381-7.
[http://dx.doi.org/10.1007/s00011-014-0710-z] [PMID: 24468890]
[62]
Hunter R, Caira M, Stellenboom N. Thiolsulfinate allicin from garlic: inspiration for a new antimicrobial agent. Ann N Y Acad Sci 2005; 1056(1): 234-41.
[http://dx.doi.org/10.1196/annals.1352.011] [PMID: 16387691]
[63]
Bayan L, Koulivand PH, Gorji A. Garlic: a review of potential therapeutic effects. Avicenna J Phytomed 2014; 4(1): 1-14.
[PMID: 25050296]
[64]
Zhou YF, Li WT, Han HC, et al. Allicin protects rat cortical neurons against mechanical trauma injury by regulating nitric oxide synthase pathways. Brain Res Bull 2014; 100: 14-21.
[http://dx.doi.org/10.1016/j.brainresbull.2013.10.013] [PMID: 24184006]
[65]
Chen W, Qi J, Feng F, et al. Neuroprotective effect of allicin against traumatic brain injury via Akt/endothelial nitric oxide synthase pathway-mediated anti-inflammatory and anti-oxidative activities. Neurochem Int 2014; 68: 28-37.
[http://dx.doi.org/10.1016/j.neuint.2014.01.015] [PMID: 24530793]
[66]
Lv R, Mao N, Wu J, et al. Neuroprotective effect of allicin in a rat model of acute spinal cord injury. Life Sci 2015; 143: 114-23.
[http://dx.doi.org/10.1016/j.lfs.2015.11.001] [PMID: 26546416]
[67]
Brasnyó P, Molnár GA, Mohás M, et al. Resveratrol improves insulin sensitivity, reduces oxidative stress and activates the Akt pathway in type 2 diabetic patients. Br J Nutr 2011; 106(3): 383-9.
[http://dx.doi.org/10.1017/S0007114511000316] [PMID: 21385509]
[68]
Ara C, Kirimlioglu H, Karabulut AB, et al. Protective effect of resveratrol against oxidative stress in cholestasis. J Surg Res 2005; 127(2): 112-7.
[http://dx.doi.org/10.1016/j.jss.2005.01.024] [PMID: 16083749]
[69]
Kesherwani V, Atif F, Yousuf S, Agrawal SK. Resveratrol protects spinal cord dorsal column from hypoxic injury by activating Nrf-2. Neuroscience 2013; 241: 80-8.
[http://dx.doi.org/10.1016/j.neuroscience.2013.03.015] [PMID: 23523995]
[70]
Du H, Ma L, Chen G, Li S. The effects of oxyresveratrol abrogates inflammation and oxidative stress in rat model of spinal cord injury. Mol Med Rep 2018; 17(3): 4067-73.
[PMID: 29257323]
[71]
Dong M, Ding W, Liao Y, et al. Polydatin prevents hypertrophy in phenylephrine induced neonatal mouse cardiomyocytes and pressure-overload mouse models. Eur J Pharmacol 2015; 746: 186-97.
[http://dx.doi.org/10.1016/j.ejphar.2014.11.012] [PMID: 25449040]
[72]
Lv R, Du L, Zhang L, Zhang Z. Polydatin attenuates spinal cord injury in rats by inhibiting oxidative stress and microglia apoptosis via Nrf2/HO-1 pathway. Life Sci 2019; 217: 119-27.
[http://dx.doi.org/10.1016/j.lfs.2018.11.053] [PMID: 30481506]
[73]
Chang C-H, Chyau CC, Hsieh CL, et al. Relevance of phenolic diterpene constituents to antioxidant activity of supercritical CO(2) extract from the leaves of rosemary. Nat Prod Res 2008; 22(1): 76-90.
[http://dx.doi.org/10.1080/14786410701591754] [PMID: 17999341]
[74]
Yesil-Celiktas O, Nartop P, Gurel A, Bedir E, Vardar-Sukan F. Determination of phenolic content and antioxidant activity of extracts obtained from Rosmarinus officinalis’ calli. J Plant Physiol 2007; 164(11): 1536-42.
[http://dx.doi.org/10.1016/j.jplph.2007.05.013] [PMID: 17913287]
[75]
Johnson JJ, Syed DN, Heren CR, Suh Y, Adhami VM, Mukhtar H. Carnosol, a dietary diterpene, displays growth inhibitory effects in human prostate cancer PC3 cells leading to G2-phase cell cycle arrest and targets the 5′-AMP-activated protein kinase (AMPK) pathway. Pharm Res 2008; 25(9): 2125-34.
[http://dx.doi.org/10.1007/s11095-008-9552-0] [PMID: 18286356]
[76]
Chen CC, Chen HL, Hsieh CW, Yang YL, Wung BS. Upregulation of NF-E2-related factor-2-dependent glutathione by carnosol provokes a cytoprotective response and enhances cell survival. Acta Pharmacol Sin 2011; 32(1): 62-9.
[http://dx.doi.org/10.1038/aps.2010.181] [PMID: 21151161]
[77]
Martin D, Rojo AI, Salinas M, et al. Regulation of heme oxygenase-1 expression through the phosphatidylinositol 3-kinase/Akt pathway and the Nrf2 transcription factor in response to the antioxidant phytochemical carnosol. J Biol Chem 2004; 279(10): 8919-29.
[http://dx.doi.org/10.1074/jbc.M309660200] [PMID: 14688281]
[78]
Wang Z-H, Xie YX, Zhang JW, et al. Carnosol protects against spinal cord injury through Nrf-2 upregulation. J Recept Signal Transduct Res 2016; 36(1): 72-8.
[http://dx.doi.org/10.3109/10799893.2015.1049358] [PMID: 26791582]
[79]
Shang AJ, Yang Y, Wang HY, et al. Spinal cord injury effectively ameliorated by neuroprotective effects of rosmarinic acid. Nutr Neurosci 2017; 20(3): 172-9.
[http://dx.doi.org/10.1080/1028415X.2015.1103460] [PMID: 26796989]
[80]
Qin T, Du R, Huang F, et al. Sinomenine activation of Nrf2 signaling prevents hyperactive inflammation and kidney injury in a mouse model of obstructive nephropathy. Free Radic Biol Med 2016; 92: 90-9.
[http://dx.doi.org/10.1016/j.freeradbiomed.2016.01.011] [PMID: 26795599]
[81]
Wu WN, Wu PF, Chen XL, et al. Sinomenine protects against ischaemic brain injury: involvement of co-inhibition of acid sensing ion channel 1a and L-type calcium channels. Br J Pharmacol 2011; 164(5): 1445-59.
[http://dx.doi.org/10.1111/j.1476-5381.2011.01487.x] [PMID: 21585344]
[82]
Yang Z, Liu Y, Yuan F, et al. Sinomenine inhibits microglia activation and attenuates brain injury in intracerebral hemorrhage. Mol Immunol 2014; 60(2): 109-14.
[http://dx.doi.org/10.1016/j.molimm.2014.03.005] [PMID: 24815539]
[83]
Zhang L, Zhang W, Zheng B, Tian N. Sinomenine Attenuates Traumatic Spinal Cord Injury by Suppressing Oxidative Stress and Inflammation via Nrf2 Pathway. Neurochem Res 2019; 44(4): 763-75.
[http://dx.doi.org/10.1007/s11064-018-02706-z] [PMID: 30603983]
[84]
Kwan CY, Daniel EE, Chen MC. Inhibition of vasoconstriction by tetramethylpyrazine: does it act by blocking the voltage-dependent Ca channel? J Cardiovasc Pharmacol 1990; 15(1): 157-62.
[http://dx.doi.org/10.1097/00005344-199001000-00025] [PMID: 1688974]
[85]
Wu W, Yu X, Luo XP, Yang SH, Zheng D. Tetramethylpyrazine protects against scopolamine-induced memory impairments in rats by reversing the cAMP/PKA/CREB pathway. Behav Brain Res 2013; 253: 212-6.
[http://dx.doi.org/10.1016/j.bbr.2013.07.052] [PMID: 23916742]
[86]
Wang C, Wang P, Zeng W, Li W. Tetramethylpyrazine improves the recovery of spinal cord injury via Akt/Nrf2/HO-1 pathway. Bioorg Med Chem Lett 2016; 26(4): 1287-91.
[http://dx.doi.org/10.1016/j.bmcl.2016.01.015] [PMID: 26786697]
[87]
Zeng M, Pan L, Qi S, et al. Systematic review of recent advances in pharmacokinetics of four classical Chinese medicines used for the treatment of cerebrovascular disease. Fitoterapia 2013; 88: 50-75.
[http://dx.doi.org/10.1016/j.fitote.2013.04.006] [PMID: 23602902]
[88]
Lin LL, Wang W, Cheng MH, Liu AJ. Protection of different components of Danshen in cerebral infarction in mice. CNS Neurosci Ther 2012; 18(6): 511-2.
[http://dx.doi.org/10.1111/j.1755-5949.2012.00331.x] [PMID: 22672306]
[89]
Sun Y, Zhu H, Wang J, Liu Z, Bi J. Isolation and purification of salvianolic acid A and salvianolic acid B from Salvia miltiorrhiza by high-speed counter-current chromatography and comparison of their antioxidant activity. J Chromatogr B Analyt Technol Biomed Life Sci 2009; 877(8-9): 733-7.
[http://dx.doi.org/10.1016/j.jchromb.2009.02.013] [PMID: 19237321]
[90]
Wang H, Li X, Zhang W, et al. Mechanism-based pharmacokinetic-pharmacodynamic modeling of salvianolic acid A effects on plasma xanthine oxidase activity and uric acid levels in acute myocardial infarction rats. Xenobiotica 2017; 47(3): 208-16.
[http://dx.doi.org/10.1080/00498254.2016.1180440] [PMID: 27165094]
[91]
Xie P, Duan Y, Guo X, Hu L, Yu M. SalA attenuates hypoxia induced endothelial endoplasmic reticulum stress and apoptosis via down-regulation of VLDL receptor expression. Cell Physiol Biochem 2015; 35(1): 17-28.
[http://dx.doi.org/10.1159/000369671] [PMID: 25547648]
[92]
Yu DS, Wang YS, Bi YL, et al. Salvianolic acid A ameliorates the integrity of blood-spinal cord barrier via miR-101/Cul3/Nrf2/HO-1 signaling pathway. Brain Res 2017; 1657: 279-87.
[http://dx.doi.org/10.1016/j.brainres.2016.12.007] [PMID: 28011395]
[93]
Zhang Z, Jin J, Shi L. Antioxidant properties of ethanolic extract from Ramulus mori (Sangzhi). Food Sci Technol Int 2009; 15(5): 435-44.
[http://dx.doi.org/10.1177/1082013209350277]
[94]
Xia P, Gao X, Duan L, Zhang W, Sun YF. Mulberrin (Mul) reduces spinal cord injury (SCI)-induced apoptosis, inflammation and oxidative stress in rats via miroRNA-337 by targeting Nrf-2. Biomed Pharmacother 2018; 107: 1480-7.
[http://dx.doi.org/10.1016/j.biopha.2018.07.082] [PMID: 30257365]
[95]
Tsao SM, Yin MC. Antioxidative and antiinflammatory activities of asiatic acid, glycyrrhizic acid, and oleanolic acid in human bronchial epithelial cells. J Agric Food Chem 2015; 63(12): 3196-204.
[http://dx.doi.org/10.1021/acs.jafc.5b00102] [PMID: 25779760]
[96]
Pakdeechote P, Bunbupha S, Kukongviriyapan U, Prachaney P, Khrisanapant W, Kukongviriyapan V. Asiatic acid alleviates hemodynamic and metabolic alterations via restoring eNOS/iNOS expression, oxidative stress, and inflammation in diet-induced metabolic syndrome rats. Nutrients 2014; 6(1): 355-70.
[http://dx.doi.org/10.3390/nu6010355] [PMID: 24441717]
[97]
Jiang W, Li M, He F, et al. Neuroprotective effect of asiatic acid against spinal cord injury in rats. Life Sci 2016; 157: 45-51.
[http://dx.doi.org/10.1016/j.lfs.2016.05.004] [PMID: 27153777]
[98]
Bendich A. β-carotene and the immune response. Proc Nutr Soc 1991; 50(2): 263-74.
[http://dx.doi.org/10.1079/PNS19910036] [PMID: 1836267]
[99]
Yamagata K, Nakayama C, Suzuki K. Dietary β-carotene regulates interleukin-1β-induced expression of apolipoprotein E in astrocytes isolated from stroke-prone spontaneously hypertensive rats. Neurochem Int 2013; 62(1): 43-9.
[http://dx.doi.org/10.1016/j.neuint.2012.11.001] [PMID: 23147682]
[100]
Mayne ST. Beta-carotene, carotenoids, and disease prevention in humans. FASEB J 1996; 10(7): 690-701.
[http://dx.doi.org/10.1096/fasebj.10.7.8635686] [PMID: 8635686]
[101]
Palozza P, Serini S, Torsello A, et al. β-carotene regulates NF kappaB DNA-binding activity by a redox mechanism in human leukemia and colon adenocarcinoma cells. J Nutr 2003; 133(2): 381-8.
[http://dx.doi.org/10.1093/jn/133.2.381] [PMID: 12566471]
[102]
Aksak Karamese S, Toktay E, Unal D, Selli J, Karamese M, Malkoc I. The protective effects of beta-carotene against ischemia/reperfusion injury in rat ovarian tissue. Acta Histochem 2015; 117(8): 790-7.
[http://dx.doi.org/10.1016/j.acthis.2015.07.006] [PMID: 26254843]
[103]
Di Tomo P, Canali R, Ciavardelli D, et al. β-Carotene and lycopene affect endothelial response to TNF-α reducing nitro-oxidative stress and interaction with monocytes. Mol Nutr Food Res 2012; 56(2): 217-27.
[http://dx.doi.org/10.1002/mnfr.201100500] [PMID: 22162208]
[104]
Zhou L, Ouyang L, Lin S, et al. Protective role of β-carotene against oxidative stress and neuroinflammation in a rat model of spinal cord injury. Int Immunopharmacol 2018; 61: 92-9.
[http://dx.doi.org/10.1016/j.intimp.2018.05.022] [PMID: 29857242]
[105]
Prasad VS, Devi PU, Rao BS, Kamath R. Radiosensitizing effect of plumbagin on mouse melanoma cells grown in vitro. Indian J Exp Biol 1996; 34(9): 857-8.
[PMID: 9014520]
[106]
Singh UV, Udupa N. Reduced toxicity and enhanced antitumor efficacy of betacyclodextrin plumbagin inclusion complex in mice bearing Ehrlich ascites carcinoma. Indian J Physiol Pharmacol 1997; 41(2): 171-5.
[PMID: 9142565]
[107]
Devi PU, Rao BS, Solomon FE. Effect of plumbagin on the radiation induced cytogenetic and cell cycle changes in mouse Ehrlich ascites carcinoma in vivo. Indian J Exp Biol 1998; 36(9): 891-5.
[PMID: 9854429]
[108]
Sugie S, Okamoto K, Rahman KM, et al. Inhibitory effects of plumbagin and juglone on azoxymethane-induced intestinal carcinogenesis in rats. Cancer Lett 1998; 127(1-2): 177-83.
[http://dx.doi.org/10.1016/S0304-3835(98)00035-4] [PMID: 9619875]
[109]
Wang CC, Chiang YM, Sung SC, Hsu YL, Chang JK, Kuo PL. Plumbagin induces cell cycle arrest and apoptosis through reactive oxygen species/c-Jun N-terminal kinase pathways in human melanoma A375.S2 cells. Cancer Lett 2008; 259(1): 82-98.
[http://dx.doi.org/10.1016/j.canlet.2007.10.005] [PMID: 18023967]
[110]
Zhang W, Cheng L, Hou Y, Si M, Zhao YP, Nie L. Plumbagin protects against spinal cord injury-induced oxidative stress and inflammation in wistar rats through Nrf-2 upregulation. Drug Res (Stuttg) 2015; 65(9): 495-9.
[PMID: 25243650]
[111]
Vartiainen N, Keksa-Goldsteine V, Goldsteins G, Koistinaho J. Aspirin provides cyclin-dependent kinase 5-dependent protection against subsequent hypoxia/reoxygenation damage in culture. J Neurochem 2002; 82(2): 329-35.
[http://dx.doi.org/10.1046/j.1471-4159.2002.00959.x] [PMID: 12124433]
[112]
Berg K, Langaas M, Ericsson M, et al. Acetylsalicylic acid treatment until surgery reduces oxidative stress and inflammation in patients undergoing coronary artery bypass grafting. Eur J Cardiothorac Surg 2013; 43(6): 1154-63.
[http://dx.doi.org/10.1093/ejcts/ezs591] [PMID: 23209276]
[113]
Wu R, Lamontagne D, de Champlain J. Antioxidative properties of acetylsalicylic Acid on vascular tissues from normotensive and spontaneously hypertensive rats. Circulation 2002; 105(3): 387-92.
[http://dx.doi.org/10.1161/hc0302.102609] [PMID: 11804997]
[114]
Zhang Y, Gordon GB. A strategy for cancer prevention: stimulation of the Nrf2-ARE signaling pathway. Mol Cancer Ther 2004; 3(7): 885-93.
[PMID: 15252150]
[115]
Kwak M-K, Itoh K, Yamamoto M, Kensler TW. Enhanced expression of the transcription factor Nrf2 by cancer chemopreventive agents: role of antioxidant response element-like sequences in the nrf2 promoter. Mol Cell Biol 2002; 22(9): 2883-92.
[http://dx.doi.org/10.1128/MCB.22.9.2883-2892.2002] [PMID: 11940647]
[116]
Rushmore TH, Morton MR, Pickett CB. The antioxidant responsive element. Activation by oxidative stress and identification of the DNA consensus sequence required for functional activity. J Biol Chem 1991; 266(18): 11632-9.
[PMID: 1646813]
[117]
Liu X-Y, Li CY, Bu H, et al. The neuroprotective potential of phase II enzyme inducer on motor neuron survival in traumatic spinal cord injury in vitro. Cell Mol Neurobiol 2008; 28(5): 769-79.
[http://dx.doi.org/10.1007/s10571-007-9219-0] [PMID: 17912625]
[118]
Koh K, Cha Y, Kim S, Kim J. tBHQ inhibits LPS-induced microglial activation via Nrf2-mediated suppression of p38 phosphorylation. Biochem Biophys Res Commun 2009; 380(3): 449-53.
[http://dx.doi.org/10.1016/j.bbrc.2009.01.082] [PMID: 19174151]
[119]
Nishizono S, Hayami T, Ikeda I, Imaizumi K. Protection against the diabetogenic effect of feeding tert-butylhydroquinone to rats prior to the administration of streptozotocin. Biosci Biotechnol Biochem 2000; 64(6): 1153-8.
[http://dx.doi.org/10.1271/bbb.64.1153] [PMID: 10923784]
[120]
Jin W, Ni H, Hou X, et al. Tert-butylhydroquinone protects the spinal cord against inflammatory response produced by spinal cord injury. Ann Clin Lab Sci 2014; 44(2): 151-7.
[PMID: 24795053]
[121]
De Sarno P, Li X, Jope RS. Regulation of Akt and glycogen synthase kinase-3 β phosphorylation by sodium valproate and lithium. Neuropharmacology 2002; 43(7): 1158-64.
[http://dx.doi.org/10.1016/S0028-3908(02)00215-0] [PMID: 12504922]
[122]
Fang X-Y, Zhang WM, Zhang CF, et al. Lithium accelerates functional motor recovery by improving remyelination of regenerating axons following ventral root avulsion and reimplantation. Neuroscience 2016; 329: 213-25.
[http://dx.doi.org/10.1016/j.neuroscience.2016.05.010] [PMID: 27185485]
[123]
Young W. Review of lithium effects on brain and blood. Cell Transplant 2009; 18(9): 951-75.
[http://dx.doi.org/10.3727/096368909X471251] [PMID: 19523343]
[124]
Kim Y, Kim J, Ahn M, Shin T. Lithium ameliorates rat spinal cord injury by suppressing glycogen synthase kinase-3β and activating heme oxygenase-1. Anat Cell Biol 2017; 50(3): 207-13.
[http://dx.doi.org/10.5115/acb.2017.50.3.207] [PMID: 29043099]
[125]
Ozturk E, Demirbilek S, Kadir But A, et al. Antioxidant properties of propofol and erythropoietin after closed head injury in rats. Prog Neuropsychopharmacol Biol Psychiatry 2005; 29(6): 922-7.
[http://dx.doi.org/10.1016/j.pnpbp.2005.04.028] [PMID: 15972243]
[126]
Chen G, Shi JX, Hang CH, Xie W, Liu J, Liu X. Inhibitory effect on cerebral inflammatory agents that accompany traumatic brain injury in a rat model: a potential neuroprotective mechanism of recombinant human erythropoietin (rhEPO). Neurosci Lett 2007; 425(3): 177-82.
[http://dx.doi.org/10.1016/j.neulet.2007.08.022] [PMID: 17825990]
[127]
Brines ML, Ghezzi P, Keenan S, et al. Erythropoietin crosses the blood-brain barrier to protect against experimental brain injury. Proc Natl Acad Sci USA 2000; 97(19): 10526-31.
[http://dx.doi.org/10.1073/pnas.97.19.10526] [PMID: 10984541]
[128]
Lu D, Mahmood A, Qu C, Goussev A, Schallert T, Chopp M. Erythropoietin enhances neurogenesis and restores spatial memory in rats after traumatic brain injury. J Neurotrauma 2005; 22(9): 1011-7.
[http://dx.doi.org/10.1089/neu.2005.22.1011] [PMID: 16156716]
[129]
Celik M, Gökmen N, Erbayraktar S, et al. Erythropoietin prevents motor neuron apoptosis and neurologic disability in experimental spinal cord ischemic injury. Proc Natl Acad Sci USA 2002; 99(4): 2258-63.
[http://dx.doi.org/10.1073/pnas.042693799] [PMID: 11854521]
[130]
Sirén A-L, Fratelli M, Brines M, et al. Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proc Natl Acad Sci USA 2001; 98(7): 4044-9.
[http://dx.doi.org/10.1073/pnas.051606598] [PMID: 11259643]
[131]
Harari & Liao. NF-κB and innate immunity in ischemic stroke. Ann N Y Acad Sci 2010; 1207: 32-40.
[132]
Digicaylioglu M, Lipton SA. Erythropoietin-mediated neuroprotection involves cross-talk between Jak2 and NF-kappaB signalling cascades. Nature 2001; 412(6847): 641-7.
[http://dx.doi.org/10.1038/35088074] [PMID: 11493922]
[133]
Kilic E, Kilic U, Soliz J, Bassetti CL, Gassmann M, Hermann DM. Brain-derived erythropoietin protects from focal cerebral ischemia by dual activation of ERK-1/-2 and Akt pathways. FASEB J 2005; 19(14): 2026-8.
[http://dx.doi.org/10.1096/fj.05-3941fje] [PMID: 16207820]
[134]
Jin W, Ming X, Hou X, et al. Protective effects of erythropoietin in traumatic spinal cord injury by inducing the Nrf2 signaling pathway activation. J Trauma Acute Care Surg 2014; 76(5): 1228-34.
[http://dx.doi.org/10.1097/TA.0000000000000211] [PMID: 24747453]
[135]
Kimura Y, et al. Hydrogen sulfide protects HT22 neuronal cells from oxidative stress. Antioxid Redox Signal 2006; 8(3-4): 661-70.
[http://dx.doi.org/10.1089/ars.2006.8.661]
[136]
Kimura Y, Kimura H. Hydrogen sulfide protects neurons from oxidative stress. FASEB J 2004; 18(10): 1165-7.
[http://dx.doi.org/10.1096/fj.04-1815fje] [PMID: 15155563]
[137]
Kesherwani V, Nelson KS, Agrawal SK. Effect of sodium hydrosulphide after acute compression injury of spinal cord. Brain Res 2013; 1527: 222-9.
[http://dx.doi.org/10.1016/j.brainres.2013.06.023] [PMID: 23806779]
[138]
Walker J, Dichter E, Lacorte G, et al. Lipoxin a4 increases survival by decreasing systemic inflammation and bacterial load in sepsis. Shock 2011; 36(4): 410-6.
[http://dx.doi.org/10.1097/SHK.0b013e31822798c1] [PMID: 21701419]
[139]
Serhan CN. Lipoxins and aspirin-triggered 15-epi-lipoxins are the first lipid mediators of endogenous anti-inflammation and resolution. Prostaglandins Leukot Essent Fatty Acids 2005; 73(3-4): 141-62.
[http://dx.doi.org/10.1016/j.plefa.2005.05.002] [PMID: 16005201]
[140]
Wu S-H, Liao PY, Dong L, Chen ZQ. Signal pathway involved in inhibition by lipoxin A(4) of production of interleukins induced in endothelial cells by lipopolysaccharide. Inflamm Res 2008; 57(9): 430-7.
[http://dx.doi.org/10.1007/s00011-008-7147-1] [PMID: 18777114]
[141]
Liu Z-Q, Zhang HB, Wang J, Xia LJ, Zhang W. Lipoxin A4 ameliorates ischemia/reperfusion induced spinal cord injury in rabbit model. Int J Clin Exp Med 2015; 8(8): 12826-33.
[PMID: 26550197]
[142]
Zhang Y, Talalay P, Cho CG, Posner GH. A major inducer of anticarcinogenic protective enzymes from broccoli: isolation and elucidation of structure. Proc Natl Acad Sci USA 1992; 89(6): 2399-403.
[http://dx.doi.org/10.1073/pnas.89.6.2399] [PMID: 1549603]
[143]
Calabrese V, et al. Cellular stress responses, the hormesis paradigm, and vitagenes: novel targets for therapeutic intervention in neurodegenerative disorders. Antioxid Redox Signal 2010; 13(11): 1763-811.
[http://dx.doi.org/10.1089/ars.2009.3074]
[144]
Ghosh N, Ghosh R, Mandal SC. Antioxidant protection: A promising therapeutic intervention in neurodegenerative disease. Free Radic Res 2011; 45(8): 888-905.
[http://dx.doi.org/10.3109/10715762.2011.574290] [PMID: 21615270]
[145]
Elbarbry F, Elrody N. Potential health benefits of sulforaphane: a review of the experimental, clinical and epidemiological evidences and underlying mechanisms. J Med Plants Res 2011; 5(4): 473-84.
[146]
Benedict AL, Mountney A, Hurtado A, et al. Neuroprotective effects of sulforaphane after contusive spinal cord injury. J Neurotrauma 2012; 29(16): 2576-86.
[http://dx.doi.org/10.1089/neu.2012.2474] [PMID: 22853439]
[147]
Wang X, de Rivero Vaccari JP, Wang H, et al. Activation of the nuclear factor E2-related factor 2/antioxidant response element pathway is neuroprotective after spinal cord injury. J Neurotrauma 2012; 29(5): 936-45.
[http://dx.doi.org/10.1089/neu.2011.1922] [PMID: 21806470]
[148]
Paoli A, Rubini A, Volek JS, Grimaldi KA. Beyond weight loss: a review of the therapeutic uses of very-low-carbohydrate (ketogenic) diets. Eur J Clin Nutr 2013; 67(8): 789-96.
[http://dx.doi.org/10.1038/ejcn.2013.116] [PMID: 23801097]
[149]
Streijger F, Plunet WT, Lee JH, et al. Ketogenic diet improves forelimb motor function after spinal cord injury in rodents. PLoS One 2013; 8(11): e78765.
[http://dx.doi.org/10.1371/journal.pone.0078765] [PMID: 24223849]
[150]
Lu Y, Yang YY, Zhou MW, et al. Ketogenic diet attenuates oxidative stress and inflammation after spinal cord injury by activating Nrf2 and suppressing the NF-κB signaling pathways. Neurosci Lett 2018; 683: 13-8.
[http://dx.doi.org/10.1016/j.neulet.2018.06.016] [PMID: 29894768]

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