Abstract
Background: Hypoxia and anoxia are dangerous and sometimes irreversible complications in the central nervous system (CNS), which in some cases lead to death.
Objective: The aim of this review was to investigate the neuroprotective effects of medicinal plants in cerebral hypoxia and anoxia.
Methods: The word hypox*, in combination with some herbal terms such as medicinal plant, phyto* and herb*, was used to search for relevant publications indexed in the Institute for Scientific Information (ISI) and PubMed from 2000-2019.
Results: Certain medicinal plants and herbal derivatives can exert their protective effects in several ways. The most important mechanisms are the inhibition of inducible nitric oxide synthase (iNOS), production of NO, inhibition of both hypoxia-inducible factor 1α and tumor necrosis factor-alpha activation, and reduction of extracellular glutamate, N-Methyl-D-aspartic and intracellular Ca (2+). In addition, they have an antioxidant activity and can adjust the expression of genes related to oxidant generation or antioxidant capacity. These plants can also inhibit lipid peroxidation, up-regulate superoxide dismutase activity and inhibit the content of malondialdehyde and lactate dehydrogenase. Moreover, they also have protective effects against cytotoxicity through down-regulation of the proteins that causes apoptosis, anti-excitatory activity, inhibition of apoptosis signaling pathway, reduction of pro-apoptotic proteins, and endoplasmic reticulum stress that causes apoptosis during hypoxia, increasing anti-apoptotic protein, inhibition of protein tyrosine kinase activation, decreasing proteases activity and DNA fragmentation, and upregulation of mitochondrial cytochrome oxidase.
Conclusion: The results indicated that medicinal plants and their compounds mainly exert their neuroprotective effects in hypoxia via regulating proteins that are related to antioxidant, anti-apoptosis and anti-inflammatory activities.
Keywords: Anti-hypoxic, medicinal plants, hypoxia, neuroprotective agents, brain hypoxia, cytotoxicity.
Graphical Abstract
[http://dx.doi.org/10.3389/fncel.2017.00248 ] [PMID: 28878624]
[http://dx.doi.org/10.3233/JAD-2011-110506 ] [PMID: 22085862]
[http://dx.doi.org/10.1136/jnnp.2010.235218 ] [PMID: 21239649]
[http://dx.doi.org/10.15171/jnp.2017.20 ] [PMID: 28975089]
[http://dx.doi.org/10.7860/JCDR/2018/36409.12042]
[PMID: 28516061]
[http://dx.doi.org/10.15171/npj.2017.03]
[http://dx.doi.org/10.15171/jnp.2017.41 ] [PMID: 28975109]
[http://dx.doi.org/10.15171/jrip.2017.25 ] [PMID: 28497089]
[http://dx.doi.org/10.1177/2156587217696927 ] [PMID: 28359161]
[http://dx.doi.org/10.3390/ijms18020265 ] [PMID: 28134843]
[http://dx.doi.org/10.1007/BF00504988 ] [PMID: 6493348]
[http://dx.doi.org/10.1159/000014065 ] [PMID: 9784635]
[http://dx.doi.org/10.1016/j.bbrc.2004.09.094 ] [PMID: 15474468]
[http://dx.doi.org/10.1186/1472-6882-4-11 ] [PMID: 15310392]
[http://dx.doi.org/10.1016/j.phymed.2003.04.001 ] [PMID: 15500258]
[PMID: 17392109]
[http://dx.doi.org/10.1016/j.phymed.2009.03.006 ] [PMID: 19406629]
[http://dx.doi.org/10.1186/1744-9081-6-61 ] [PMID: 20955613]
[http://dx.doi.org/10.3390/molecules16086322 ] [PMID: 21792150]
[http://dx.doi.org/10.1186/2008-2231-20-42 ] [PMID: 23351182]
[http://dx.doi.org/10.3109/13880209.2014.908395 ] [PMID: 25026346]
[http://dx.doi.org/10.1016/j.hermed.2014.04.005]
[PMID: 25730808]
[http://dx.doi.org/10.4103/0253-7613.150372 ] [PMID: 25821320]
[http://dx.doi.org/10.1007/s12017-016-8401-2 ] [PMID: 27165113]
[http://dx.doi.org/10.1007/s12035-017-0776-z ] [PMID: 28942553]
[http://dx.doi.org/10.18805/lr.v0iOF.3544]
[http://dx.doi.org/10.1142/S0192415X17500914 ] [PMID: 29121798]
[http://dx.doi.org/10.1007/s11064-017-2395-5 ] [PMID: 28861754]
[http://dx.doi.org/10.1016/0378-8741(93)90069-H ] [PMID: 8145576]
[http://dx.doi.org/10.1254/jjp.64.171 ] [PMID: 8022119]
[http://dx.doi.org/10.1055/s-2000-11128 ] [PMID: 10763582]
[http://dx.doi.org/10.1016/j.jep.2004.12.001 ] [PMID: 15740883]
[http://dx.doi.org/10.1007/s11655-009-0128-6 ] [PMID: 19407951]
[http://dx.doi.org/10.1016/j.jep.2011.01.033 ] [PMID: 21315142]
[http://dx.doi.org/10.1016/j.neuropharm.2012.05.035 ] [PMID: 22659084]
[http://dx.doi.org/10.1248/bpb.35.355 ] [PMID: 22382321]
[http://dx.doi.org/10.1016/j.jep.2014.04.022 ] [PMID: 24751364]
[http://dx.doi.org/10.1007/s11655-013-1657-6 ] [PMID: 24307315]
[http://dx.doi.org/10.1016/j.jep.2012.10.046 ] [PMID: 23127652]
[http://dx.doi.org/10.1371/journal.pone.0078281 ] [PMID: 24205180]
[PMID: 25206471]
[PMID: 26770451]
[http://dx.doi.org/10.3892/etm.2017.4286 ] [PMID: 28565820]
[http://dx.doi.org/10.1007/s11094-017-1673-5]
[http://dx.doi.org/10.1155/2017/3209219 ] [PMID: 29234383]
[http://dx.doi.org/10.1016/j.jphs.2017.11.005 ] [PMID: 29336875]
[http://dx.doi.org/10.1016/j.phymed.2018.04.025 ] [PMID: 29895489]
[http://dx.doi.org/10.1248/bpb.27.1081 ] [PMID: 15256744]
[PMID: 15274758]
[http://dx.doi.org/10.1203/01.PDR.0000180550.99162.BC ] [PMID: 16189210]
[http://dx.doi.org/10.1055/s-2006-951709 ] [PMID: 17089323]
[http://dx.doi.org/10.1055/s-2007-981523 ] [PMID: 17583824]
[http://dx.doi.org/10.1080/13880200701538666]
[http://dx.doi.org/10.1248/bpb.30.189 ] [PMID: 17202685]
[http://dx.doi.org/10.1021/np0605182 ] [PMID: 17381154]
[http://dx.doi.org/10.1179/016164107X229894 ] [PMID: 17716390]
[http://dx.doi.org/10.1016/j.neulet.2008.09.064 ] [PMID: 18838103]
[http://dx.doi.org/10.1556/APhysiol.99.2012.3.8 ] [PMID: 22982719]
[PMID: 25317299]
[http://dx.doi.org/10.1016/j.brainres.2014.02.021 ] [PMID: 24560603]
[http://dx.doi.org/10.1556/APhysiol.96.2009.2.6 ] [PMID: 19457765]
[http://dx.doi.org/10.1016/j.jep.2009.07.034 ] [PMID: 19665536]
[http://dx.doi.org/10.1186/1423-0127-16-9 ] [PMID: 19272172]
[http://dx.doi.org/10.1016/j.neuroscience.2008.10.003 ] [PMID: 18976694]
[http://dx.doi.org/10.1007/s10571-016-0372-1 ] [PMID: 27059741]
[http://dx.doi.org/10.1016/j.etap.2017.01.022 ] [PMID: 28192752]
[PMID: 22229507]
[PMID: 28392899]
[http://dx.doi.org/10.1016/j.jep.2013.08.011 ] [PMID: 24012966]
[http://dx.doi.org/10.1002/ptr.3500 ] [PMID: 21538624]
[http://dx.doi.org/10.1159/000325202 ] [PMID: 21325818]
[http://dx.doi.org/10.1016/j.lfs.2014.07.020 ] [PMID: 25064828]
[PMID: 23983340]
[http://dx.doi.org/10.1007/s12272-012-0620-y ] [PMID: 22870822]
[http://dx.doi.org/10.1016/j.jep.2012.03.042 ] [PMID: 22472112]
[PMID: 25558222]
[http://dx.doi.org/10.1016/j.jep.2011.08.063 ] [PMID: 21920425]
[http://dx.doi.org/10.3923/pjbs.2013.1687.1697 ] [PMID: 24506035]
[http://dx.doi.org/10.1016/j.autneu.2012.11.004 ] [PMID: 23218834]
[http://dx.doi.org/10.12659/MSM.898921 ] [PMID: 28009855]
[http://dx.doi.org/10.1016/j.biopha.2016.10.007 ] [PMID: 27764754]
[http://dx.doi.org/10.1007/s10072-013-1288-x ] [PMID: 23344742]
[http://dx.doi.org/10.1007/s10072-014-1718-4 ] [PMID: 24651933]
[http://dx.doi.org/10.1016/j.ejphar.2016.11.038 ] [PMID: 27889433]
[http://dx.doi.org/10.3892/mmr.2014.2577 ] [PMID: 25241777]
[http://dx.doi.org/10.1007/s00210-014-1006-0 ] [PMID: 24947869]
[http://dx.doi.org/10.1016/j.neuropharm.2015.07.007 ] [PMID: 26187393]
[http://dx.doi.org/10.1371/journal.pone.0109923 ] [PMID: 25334016]
[http://dx.doi.org/10.1007/s12035-014-8948-6 ] [PMID: 25367882]
[http://dx.doi.org/10.1016/j.ejphar.2015.09.042 ] [PMID: 26420356]
[http://dx.doi.org/10.1038/srep14507 ] [PMID: 26419512]
[http://dx.doi.org/10.1016/j.neuint.2015.06.008 ] [PMID: 26120022]
[http://dx.doi.org/10.1016/j.jns.2015.12.026 ] [PMID: 26810525]
[http://dx.doi.org/10.1007/s10571-016-0398-4 ] [PMID: 27380043]
[http://dx.doi.org/10.12659/MSM.897640 ] [PMID: 27794583]
[http://dx.doi.org/10.1016/j.jep.2016.06.017 ] [PMID: 27288754]
[http://dx.doi.org/10.3390/nu8010041 ] [PMID: 26771636]
[http://dx.doi.org/10.1124/jpet.115.230359 ] [PMID: 26892460]
[http://dx.doi.org/10.1007/s11064-018-2538-3 ] [PMID: 29696512]
[http://dx.doi.org/10.1016/j.pnpbp.2016.11.005 ] [PMID: 27889412]
[PMID: 29513961]
[http://dx.doi.org/10.1016/j.brainres.2016.12.007 ] [PMID: 28011395]
[http://dx.doi.org/10.5742/MEWFM.2017.93162]
[http://dx.doi.org/10.1016/j.abb.2015.01.029 ] [PMID: 25841340]
[http://dx.doi.org/10.1016/S0166-2236(96)10074-6 ] [PMID: 9061868]
[http://dx.doi.org/10.1152/physrev.00029.2006 ] [PMID: 17237348]
[http://dx.doi.org/10.5114/ceji.2015.56973 ] [PMID: 27095931]
[http://dx.doi.org/10.4103/ATMPH.ATMPH_174_17]
[http://dx.doi.org/10.1002/ptr.5837 ] [PMID: 28568565]
[http://dx.doi.org/10.12991/marupj.311815]
[http://dx.doi.org/10.15419/bmrat.v5i1.408]
[http://dx.doi.org/10.1186/s40199-015-0115-8 ] [PMID: 26063234]
[http://dx.doi.org/10.4155/fsoa-2018-0096 ] [PMID: 30906567]
[http://dx.doi.org/10.3389/fphar.2012.00060 ] [PMID: 22518104]
[http://dx.doi.org/10.3390/brainsci6010006 ] [PMID: 26901230]
[http://dx.doi.org/10.3892/mmr.2017.6277 ] [PMID: 28259912]
[http://dx.doi.org/10.1016/S0166-2236(00)01746-X ] [PMID: 11250007]
[http://dx.doi.org/10.1124/dmd.117.078436 ] [PMID: 29061584]
[PMID: 28521703 ]