The Ethanolic Extract of Polygala paniculata L. Blocks Panx1 Channels and Reduces Ischemic Brain Infarct in a Dose- and Sex-Dependent Way.
Polygala paniculata L
Neuroprotection
Pannexin-1
Photothrombotic ischemia
Journal
Molecular neurobiology
ISSN: 1559-1182
Titre abrégé: Mol Neurobiol
Pays: United States
ID NLM: 8900963
Informations de publication
Date de publication:
13 Sep 2024
13 Sep 2024
Historique:
received:
27
05
2024
accepted:
27
08
2024
medline:
14
9
2024
pubmed:
14
9
2024
entrez:
13
9
2024
Statut:
aheadofprint
Résumé
Polygala paniculata L. is a native plant from tropical America. The therapeutic potential of the hydroalcoholic extract of P. paniculata (HEPp) has been scientifically explored due to folk medicine reports on its action against several afflictions. HEPp contains several bioactive molecules with neuroprotective activities, making it a promising candidate for stroke treatment. This study used electrophysiological, biochemical, and in vivo experiments to evaluate the molecular mechanisms underlying HEPp as a neuroprotective therapy for stroke targeting Pannexin-1 (Panx1). Panx1 is a non-selective channel that opens during ischemia and contributes to neuronal death. HEPp was not toxic to cortical neurons and pre-treatment with the extract reduced neuronal death promoted by oxygen and glucose deprivation in a dose-dependent manner. Additionally, HEPp blocked Panx1 currents in a dose-dependent manner and the effect, which was shown to be partially due to rutin. Animals submitted to photothrombosis and post-treated with HEPp had reduced infarct volume, and the effective dose was lower in males (1 mg/kg) than in females (10 mg/kg). On the other hand, in Panx1 KD mice (50% Panx1 levels), the acute treatment reduced the infarct volume only in males. Upon chronic treatment with HEPp, a reduction in Panx1 protein levels was observed. The current study provides reliable evidence of the neuroprotective properties of HEPp in both in vitro and in vivo models of stroke. The underlying mechanism involves, at least in part, the inhibition of Panx1 channel function and possibly downregulation of protein levels, suppressing the secondary events that lead to apoptosis and inflammation.
Identifiants
pubmed: 39271622
doi: 10.1007/s12035-024-04453-5
pii: 10.1007/s12035-024-04453-5
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Références
Feigin VL, Stark BA, Johnson CO et al (2021) Global, regional, and national burden of stroke and its risk factors, 1990–2019: A systematic analysis for the Global Burden of Disease Study 2019. Lancet Neurol 20:1–26. https://doi.org/10.1016/S1474-4422(21)00252-0/ATTACHMENT/817F5B22-098B-42BB-AF7E-C7DAF55AAD0B/MMC1.PDF
doi: 10.1016/S1474-4422(21)00252-0/ATTACHMENT/817F5B22-098B-42BB-AF7E-C7DAF55AAD0B/MMC1.PDF
Thayabaranathan T, Kim J, Cadilhac DA et al (2022) Global stroke statistics 2022. Int J Stroke 17:946–956
doi: 10.1177/17474930221123175
pubmed: 35975986
pmcid: 9980380
Tsao CW, Aday AW, Almarzooq ZI et al (2022) Heart Disease and Stroke Statistics-2022 Update: A Report From the American Heart Association. Circulation 145:e153–e639. https://doi.org/10.1161/CIR.0000000000001052/FORMAT/EPUB
doi: 10.1161/CIR.0000000000001052/FORMAT/EPUB
pubmed: 35078371
Ma R, Xie Q, Li Y et al (2020) Animal models of cerebral ischemia: A review. Biomed Pharmacother 131:110686. https://doi.org/10.1016/J.BIOPHA.2020.110686
doi: 10.1016/J.BIOPHA.2020.110686
pubmed: 32937247
Daniele SG, Trummer G, Hossmann KA et al (2021) Brain vulnerability and viability after ischaemia. Nature Rev Neurosci 22(9):553–572. https://doi.org/10.1038/s41583-021-00488-y
doi: 10.1038/s41583-021-00488-y
Enomoto M, Endo A, Yatsushige H et al (2019) Clinical effects of early edaravone use in acute ischemic stroke patients treated by endovascular reperfusion therapy. Stroke 50:652–658. https://doi.org/10.1161/STROKEAHA.118.023815
doi: 10.1161/STROKEAHA.118.023815
pubmed: 30741623
Liebeskind DS, Derdeyn CP, Wechsler LR (2018) Emerging considerations in developing and evaluating new stroke therapies. Stroke 49:2241–2247. https://doi.org/10.1161/STROKEAHA.118.021424
doi: 10.1161/STROKEAHA.118.021424
pubmed: 30355006
Noor F, Qamar MTU, Ashfaq UA, et al (2022) Network Pharmacology Approach for Medicinal Plants: Review and Assessment. Pharmaceuticals (Basel) 15:. https://doi.org/10.3390/PH15050572
Saver JL, Albers GW, Dunn B et al (2009) Stroke therapy academic industry roundtable (STAIR) recommendations for extended window acute stroke therapy trials. Stroke 40:2594–2600. https://doi.org/10.1161/STROKEAHA.109.552554
doi: 10.1161/STROKEAHA.109.552554
pubmed: 19478212
pmcid: 2761073
Wink M (2015) Modes of Action of Herbal Medicines and Plant Secondary Metabolites. Medicines 2:251. https://doi.org/10.3390/MEDICINES2030251
doi: 10.3390/MEDICINES2030251
pubmed: 28930211
pmcid: 5456217
Wang Y, Wu H, Han Z, et al (2022) Guhong injection promotes post-stroke functional recovery via attenuating cortical inflammation and apoptosis in subacute stage of ischemic stroke. Phytomedicine 99:. https://doi.org/10.1016/J.PHYMED.2022.154034
Calixto JB (2019) The role of natural products in modern drug discovery. An Acad Bras Cienc 91. https://doi.org/10.1590/0001-3765201920190105
Dutra RC, Campos MM, Santos ARSS, Calixto JB (2016) Medicinal plants in Brazil : Pharmacological studies, drug discovery, challenges and perspectives. Pharmacol Res 112:4–29. https://doi.org/10.1016/J.PHRS.2016.01.021
doi: 10.1016/J.PHRS.2016.01.021
pubmed: 26812486
Andrae-Marobela K, Ghislain FW, Okatch H, Majinda RRT (2013) Polyphenols: A Diverse Class of Multi-Target Anti-HIV-1 Agents. Curr Drug Metab 14:392–413. https://doi.org/10.2174/13892002113149990095
doi: 10.2174/13892002113149990095
pubmed: 23330927
Fernandes F, Barroso MF, De Simone A et al (2022) Multi-target neuroprotective effects of herbal medicines for Alzheimer’s disease. J Ethnopharmacol 290:115107. https://doi.org/10.1016/J.JEP.2022.115107
doi: 10.1016/J.JEP.2022.115107
pubmed: 35176467
Shoaib S, Islam N, Yusuf N (2022) Phytocompounds from the medicinal and dietary plants: Multi-target agents for cancer prevention and therapy. Curr Med Chem 29:. https://doi.org/10.2174/0929867329666220301114251
Klein LCJ, de Andrade SF, Cechinel Filho V et al (2012) A pharmacognostic approach to the polygala genus: Phytochemical and pharmacological aspects. Chem Biodivers 9:181–209. https://doi.org/10.1002/cbdv.201000319
doi: 10.1002/cbdv.201000319
pubmed: 22344900
Lacaille-Dubois M-AA, Delaude CC, Mitaine-Offer A-CC (2020) A review on the phytopharmacological studies of the genus Polygala. J Ethnopharmacol 249:112417. https://doi.org/10.1016/j.jep.2019.112417
doi: 10.1016/j.jep.2019.112417
pubmed: 31765761
Pradi L, Andrade TES, Lacerda JWF et al (2023) The Antinociceptive Effect of a Hydroalcoholic Extract of Polygala altomontana and Its Chemical Profile Using UPLC-ESI-QTOF-HR-MS. Chem Biodivers 20:e202200715. https://doi.org/10.1002/CBDV.202200715
doi: 10.1002/CBDV.202200715
pubmed: 36490384
Tizziani T, Pereira M, Venzke D et al (2018) A new xanthone as a chemical marker of four Polygala species (Polygalaceae). Biochem Syst Ecol 78:46–48. https://doi.org/10.1016/J.BSE.2018.03.007
doi: 10.1016/J.BSE.2018.03.007
Da Rocha LF, Soares KC, Rattmann YD et al (2011) Vasorelaxant and hypotensive effects of the extract and the isolated flavonoid rutin obtained from Polygala paniculata L. J Pharm Pharmacol 63:875–881
doi: 10.1111/j.2042-7158.2010.01240.x
Johann S, Mendes BG, Missau FC et al (2011) Antifungal activity of five species of Polygala. Braz J Microbiol 42:1065–1075. https://doi.org/10.1590/S1517-83822011000300027
doi: 10.1590/S1517-83822011000300027
pubmed: 24031724
pmcid: 3768791
Pizzolatti MG, Koga AH, Grisard EC, Steindel M (2003) Trypanocidal activity of extracts from Brazilian Atlantic Rain Forest plant species. Phytomedicine 10:422–426. https://doi.org/10.1078/0944-7113-00252
doi: 10.1078/0944-7113-00252
pubmed: 12834008
Tizziani T, Venzke D, Ruani AP, et al (2017) Antitumor screening of crude extracts of ten medicinal plants of Polygala genus from Southern Brazil. J Appl Pharm Sci 7,:079–083. https://doi.org/10.7324/JAPS.2017.71011
Bettio LEB, MacHado DG, Cunha MP et al (2011) Antidepressant-like effect of extract from Polygala paniculata: Involvement of the monoaminergic systems. Pharm Biol 49:1277–1285. https://doi.org/10.3109/13880209.2011.621958
doi: 10.3109/13880209.2011.621958
pubmed: 22077163
Farina M, Franco JL, Ribas CM et al (2005) Protective effects of Polygala paniculata extract against methylmercury-induced neurotoxicity in mice. J Pharm Pharmacol 57:1503–1508
doi: 10.1211/jpp.57.11.0017
pubmed: 16259784
Lapa F, Da R, Freitas CS, Baggio CH et al (2007) Gastroprotective activity of the hydroalcoholic extract obtained from Polygala paniculate L. in rats. J Pharma Pharmacol 59:1413–1419
doi: 10.1211/jpp.59.10.0012
Lapa FDR, Gadotti VM, Missau FC et al (2009) Antinociceptive properties of the hydroalcoholic extract and the flavonoid rutin obtained from Polygala paniculata L. in Mice. Basic Clin Pharmacol Toxicol 104:306–315. https://doi.org/10.1111/J.1742-7843.2008.00365.X
doi: 10.1111/J.1742-7843.2008.00365.X
pubmed: 19281602
Franco JL, Braga HC, Stringari J et al (2007) Mercurial-induced hydrogen peroxide generation in mouse brain mitochondria: Protective effects of quercetin. Chem Res Toxicol 20:1919–1926. https://doi.org/10.1021/TX7002323
doi: 10.1021/TX7002323
pubmed: 17944542
Zhou Q, Sheng M (2013) NMDA receptors in nervous system diseases. Neuropharmacology 74:69–75. https://doi.org/10.1016/J.NEUROPHARM.2013.03.030
doi: 10.1016/J.NEUROPHARM.2013.03.030
pubmed: 23583930
Thompson RJ, Zhou N, MacVicar BA (2006) Ischemia opens neuronal gap junction hemichannels. Science (1979) 312:. https://doi.org/10.1126/science.1126241
Bravo D, Maturana CJ, Pelissier T et al (2015) Interactions of pannexin 1 with NMDA and P2X7 receptors in central nervous system pathologies: Possible role on chronic pain. Pharmacol Res 101:86–93. https://doi.org/10.1016/J.PHRS.2015.07.016
doi: 10.1016/J.PHRS.2015.07.016
pubmed: 26211949
Yeung AK, Patil CS, Jackson MF (2020) Pannexin-1 in the CNS: Emerging concepts in health and disease. J Neurochem 154:468–485
doi: 10.1111/jnc.15004
pubmed: 32162337
Sosinsky GE, Boassa D, Dermietzel R, et al (2011) Pannexin channels are not gap junction hemichannels. Channels (Austin) 5:. https://doi.org/10.4161/CHAN.5.3.15765
Bruzzone R, Hormuzdi SG, Barbe MT et al (2003) Pannexins, a family of gap junction proteins expressed in brain. Proc Natl Acad Sci U S A 100:13644–13649. https://doi.org/10.1073/PNAS.2233464100/SUPPL_FILE/3464FIG6LEGEND.HTML
doi: 10.1073/PNAS.2233464100/SUPPL_FILE/3464FIG6LEGEND.HTML
pubmed: 14597722
pmcid: 263867
Ray A, Zoidl G, Weickert S et al (2005) Site-specific and developmental expression of pannexin1 in the mouse nervous system. Eur J Neurosci 21:3277–3290. https://doi.org/10.1111/J.1460-9568.2005.04139.X
doi: 10.1111/J.1460-9568.2005.04139.X
pubmed: 16026466
Zoidl G, Petrasch-Parwez E, Ray A et al (2007) Localization of the pannexin1 protein at postsynaptic sites in the cerebral cortex and hippocampus. Neuroscience 146:9–16. https://doi.org/10.1016/J.NEUROSCIENCE.2007.01.061
doi: 10.1016/J.NEUROSCIENCE.2007.01.061
pubmed: 17379420
Bravo D, Zepeda-Morales K, Maturana CJ, et al (2022) NMDA and P2X7 Receptors Require Pannexin 1 Activation to Initiate and Maintain Nociceptive Signaling in the Spinal Cord of Neuropathic Rats. Int J Molecul Sci 23:6705 23:6705. https://doi.org/10.3390/IJMS23126705
Li S, Bjelobaba I, Stojilkovic SS (2018) Interactions of Pannexin1 channels with purinergic and NMDA receptor channels. Biochimica et Biophysica Acta (BBA) - Biomembranes 1860:166–173. https://doi.org/10.1016/J.BBAMEM.2017.03.025
Li YL, Liu F, Zhang YY et al (2021) NMDAR1-Src-Pannexin1 Signal Pathway in the Trigeminal Ganglion Contributed to Orofacial Ectopic Pain Following Inferior Alveolar Nerve Transection. Neuroscience 466:77–86. https://doi.org/10.1016/J.NEUROSCIENCE.2021.04.032
doi: 10.1016/J.NEUROSCIENCE.2021.04.032
pubmed: 33965504
Bialecki J, Werner A, Weilinger NL et al (2020) Suppression of Presynaptic Glutamate Release by Postsynaptic Metabotropic NMDA Receptor Signalling to Pannexin-1. J Neurosci 40:729–742. https://doi.org/10.1523/JNEUROSCI.0257-19.2019
doi: 10.1523/JNEUROSCI.0257-19.2019
pubmed: 31818976
pmcid: 6975291
Crocetti L, Guerrini G, Puglioli S et al (2021) Design and synthesis of the first indole-based blockers of Panx-1 channel. Eur J Med Chem 223:113650. https://doi.org/10.1016/J.EJMECH.2021.113650
doi: 10.1016/J.EJMECH.2021.113650
pubmed: 34174741
Wei R, Bao W, He F et al (2020) Pannexin1 Channel Inhibitor (10panx) Protects Against Transient Focal Cerebral Ischemic Injury by Inhibiting RIP3 Expression and Inflammatory Response in Rats. Neuroscience 437:23–33. https://doi.org/10.1016/J.NEUROSCIENCE.2020.02.042
doi: 10.1016/J.NEUROSCIENCE.2020.02.042
pubmed: 32173418
Tizziani T, Venzke D, Ruani AP et al (2020) Dihydrostyryl-2-pyrone as a chemical marker of three non-xanthone-producing Polygala species (Polygalaceae). Biochem Syst Ecol 90:104034. https://doi.org/10.1016/J.BSE.2020.104034
doi: 10.1016/J.BSE.2020.104034
Tizziani T, Venzke D, Ruani AP et al (2018) Phytochemical and chemotaxonomic study of Polygala altomontana (Polygalaceae). Biochem Syst Ecol 77:1–3. https://doi.org/10.1016/J.BSE.2017.12.003
doi: 10.1016/J.BSE.2017.12.003
Cregan SP, Fortin A, MacLaurin JG et al (2002) Apoptosis-inducing factor is involved in the regulation of caspase-independent neuronal cell death. J Cell Biol 158:507–517. https://doi.org/10.1083/JCB.200202130
doi: 10.1083/JCB.200202130
pubmed: 12147675
pmcid: 2173837
Ciccarelli R, D’Alimonte I, Ballerini P et al (2007) Molecular Signalling Mediating the Protective Effect of A1 Adenosine and mGlu3 Metabotropic Glutamate Receptor Activation against Apoptosis by Oxygen/Glucose Deprivation in Cultured Astrocytes. Mol Pharmacol 71:1369–1380. https://doi.org/10.1124/MOL.106.031617
doi: 10.1124/MOL.106.031617
pubmed: 17293559
Sandilos JK, Chiu YH, Chekeni FB et al (2012) Pannexin 1, an ATP release channel, is activated by caspase cleavage of its pore-associated C-terminal autoinhibitory region. J Biol Chem 287:11303–11311. https://doi.org/10.1074/jbc.M111.323378
doi: 10.1074/jbc.M111.323378
pubmed: 22311983
pmcid: 3322839
Nomura T, Taruno A, Shiraishi M, et al (2017) Current-direction/amplitude-dependent single channel gating kinetics of mouse pannexin 1 channel: a new concept for gating kinetics. Scientific Reports 2017 7:1 7:1–13. https://doi.org/10.1038/s41598-017-10921-x
Boyce AKJ, Fouad Y, Gom RC, et al (2023) Unilateral hippocampal stroke in freely behaving mice reveals sex differences in contralesional spreading depolarization and associated behavior. bioRxiv 2023.08.31.555814. https://doi.org/10.1101/2023.08.31.555814
Watson BD, Dietrich WD, Busto R et al (1985) Induction of reproducible brain infarction by photochemically initiated thrombosis. Ann Neurol 17:497–504. https://doi.org/10.1002/ANA.410170513
doi: 10.1002/ANA.410170513
pubmed: 4004172
Labat-gest V, Tomasi S (2013) Photothrombotic ischemia: a minimally invasive and reproducible photochemical cortical lesion model for mouse stroke studies. J Vis Exp. https://doi.org/10.3791/50370
doi: 10.3791/50370
pubmed: 23770844
pmcid: 3727176
Goncalves LV, Herlinger ALAL, Ferreira TAATAA et al (2018) Environmental enrichment cognitive neuroprotection in an experimental model of cerebral ischemia: biochemical and molecular aspects. Behav Brain Res 348:171–183. https://doi.org/10.1016/j.bbr.2018.04.023
doi: 10.1016/j.bbr.2018.04.023
pubmed: 29684474
Weilinger NL, Tang PL, Thompson RJ (2012) Anoxia-Induced NMDA Receptor Activation Opens Pannexin Channels via Src Family Kinases. J Neurosci 32:12579–12588. https://doi.org/10.1523/JNEUROSCI.1267-12.2012
doi: 10.1523/JNEUROSCI.1267-12.2012
pubmed: 22956847
pmcid: 6621249
Thompson RJ, Jackson MF, Olah ME, et al (2008) Activation of pannexin-1 hemichannels augments aberrant bursting in the hippocampus. Science (1979) 322:. https://doi.org/10.1126/science.1165209
Weilinger NL, Lohman AW, Rakai BD, et al (2016) Metabotropic NMDA receptor signaling couples Src family kinases to pannexin-1 during excitotoxicity. Nat Neurosci 19:. https://doi.org/10.1038/nn.4236
Jiang N, Wei S, Zhang Y et al (2021) Protective Effects and Mechanism of Radix Polygalae Against Neurological Diseases as Well as Effective Substance. Front Psychiatry 12:1837. https://doi.org/10.3389/FPSYT.2021.688703/BIBTEX
doi: 10.3389/FPSYT.2021.688703/BIBTEX
Lee HJ, Yeon Ban J, Koh SB et al (2004) Polygalae Radix Extract Protects Cultured Rat Granule Cells Against Damage Induced by NMDA. Am J Chin Med (Gard City N Y) 32:599–610. https://doi.org/10.1142/S0192415X04002235
doi: 10.1142/S0192415X04002235
Zhang L, Yong YY, Deng L et al (2023) Therapeutic potential of Polygala saponins in neurological diseases. Phytomedicine 108:154483. https://doi.org/10.1016/J.PHYMED.2022.154483
doi: 10.1016/J.PHYMED.2022.154483
pubmed: 36260972
Xie W, Wulin H, Shao G et al (2020) Polygalasaponin F inhibits neuronal apoptosis induced by oxygen-glucose deprivation and reoxygenation through the PI3K/Akt pathway. Basic Clin Pharmacol Toxicol 127:196–204. https://doi.org/10.1111/BCPT.13408
doi: 10.1111/BCPT.13408
pubmed: 32237267
Shin IJ, Son SU, Park H et al (2014) Preclinical Evidence of Rapid-Onset Antidepressant-Like Effect in Radix Polygalae Extract. PLoS ONE 9:e88617. https://doi.org/10.1371/JOURNAL.PONE.0088617
doi: 10.1371/JOURNAL.PONE.0088617
pubmed: 24520403
pmcid: 3919798
Sun C, Cao XC, Liu ZY et al (2022) Polygalasaponin F protects hippocampal neurons against glutamate-induced cytotoxicity. Neural Regen Res 17:178. https://doi.org/10.4103/1673-5374.314321
doi: 10.4103/1673-5374.314321
pubmed: 34100454
Swan JH, Meldrum BS (2016) Protection by NMDA Antagonists against Selective Cell Loss following Transient Ischaemia. https://doi.org/10.1038/jcbfm.1990.63
Diener H-C, Alkhedr A, Busse O, et al (2014) Treatment of acute ischaemic stroke with the low-affinity, use-dependent NMDA antagonist AR-R15896AR. J Neurol 2002 249:5 249:561–568. https://doi.org/10.1007/S004150200065
Ikonomidou C, Turski L (2002) Why did NMDA receptor antagonists fail clinical trials for stroke and traumatic brain injury? Lancet Neurol 1:383–386. https://doi.org/10.1016/S1474-4422(02)00164-3
doi: 10.1016/S1474-4422(02)00164-3
pubmed: 12849400
Bu F, Nie L, Quinn JP, Wang M (2020) Sarcoma Family Kinase-Dependent Pannexin-1 Activation after Cortical Spreading Depression Is Mediated by NR2A-Containing Receptors. Int J Mol Sci 21:. https://doi.org/10.3390/IJMS21041269
Beyer EC, Berthoud VM (2018) Gap junction gene and protein families: Connexins, innexins, and pannexins. Biochim Biophys Acta Biomembr 1860:5–8. https://doi.org/10.1016/J.BBAMEM.2017.05.016
doi: 10.1016/J.BBAMEM.2017.05.016
pubmed: 28559187
Jordan K, Chodock R, Hand AR, Laird DW (2001) The origin of annular junctions: a mechanism of gap junction internalization. J Cell Sci 114:763–773. https://doi.org/10.1242/JCS.114.4.763
doi: 10.1242/JCS.114.4.763
pubmed: 11171382
Penuela S, Bhalla R, Gong XQ et al (2007) Pannexin 1 and pannexin 3 are glycoproteins that exhibit many distinct characteristics from the connexin family of gap junction proteins. J Cell Sci 120:3772–3783. https://doi.org/10.1242/JCS.009514
doi: 10.1242/JCS.009514
pubmed: 17925379
Boyce AKJ, Kim MS, Wicki-Stordeur LE, Swayne LA (2015) ATP stimulates pannexin 1 internalization to endosomal compartments. Biochemical Journal 470:319–330. https://doi.org/10.1042/BJ20141551
doi: 10.1042/BJ20141551
pubmed: 26195825
Boyce AKJ, Swayne LA (2017) P2X7 receptor cross-talk regulates ATP-induced pannexin 1 internalization. Biochemical J 474:2133–2144. https://doi.org/10.1042/BCJ20170257
doi: 10.1042/BCJ20170257
Crocetti L, Guerrini G, Giovannoni MP, et al (2022) New Panx-1 Blockers: Synthesis, Biological Evaluation and Molecular Dynamic Studies. Int J Molecul Sci 2022, Vol 23, Page 4827 23:4827. https://doi.org/10.3390/IJMS23094827
Chang A, Chang Y, Wang SJ (2022) Rutin prevents seizures in kainic acid-treated rats: evidence of glutamate levels, inflammation and neuronal loss modulation. Food Funct 13:10401–10414. https://doi.org/10.1039/D2FO01490D
doi: 10.1039/D2FO01490D
pubmed: 36148811
Sun XY, Li LJ, Dong QX et al (2021) Rutin prevents tau pathology and neuroinflammation in a mouse model of Alzheimer’s disease. J Neuroinflam 18:1–14. https://doi.org/10.1186/S12974-021-02182-3/FIGURES/7
doi: 10.1186/S12974-021-02182-3/FIGURES/7
Elmazoglu Z, Galván-Arzate S, Aschner M et al (2021) Redox-active phytoconstituents ameliorate cell damage and inflammation in rat hippocampal neurons exposed to hyperglycemia+Aβ1-42 peptide. Neurochem Int 145:104993. https://doi.org/10.1016/J.NEUINT.2021.104993
doi: 10.1016/J.NEUINT.2021.104993
pubmed: 33610590
Ouyang Q, Liu K, Zhu Q et al (2022) Brain-Penetration and Neuron-Targeting DNA Nanoflowers Co-Delivering miR-124 and Rutin for Synergistic Therapy of Alzheimer’s Disease. Small 18:2107534. https://doi.org/10.1002/SMLL.202107534
doi: 10.1002/SMLL.202107534
Campanile M, Cuomo O, Brancaccio P et al (2022) Ruta graveolens water extract (RGWE) ameliorates ischemic damage and improves neurological deficits in a rat model of transient focal brain ischemia. Biomed Pharmacother 154:113587. https://doi.org/10.1016/J.BIOPHA.2022.113587
doi: 10.1016/J.BIOPHA.2022.113587
pubmed: 36029540
Sanchez-Arias JC, van der Slagt E, Vecchiarelli HA et al (2021) Purinergic signaling in nervous system health and disease: Focus on pannexin 1. Pharmacol Ther 225:107840. https://doi.org/10.1016/J.PHARMTHERA.2021.107840
doi: 10.1016/J.PHARMTHERA.2021.107840
pubmed: 33753132
Ardiles AO, Flores-Muñoz C, Toro-Ayala G et al (2014) Pannexin 1 regulates bidirectional hippocampal synaptic plasticity in adult mice. Front Cell Neurosci 8:326. https://doi.org/10.3389/FNCEL.2014.00326/BIBTEX
doi: 10.3389/FNCEL.2014.00326/BIBTEX
pubmed: 25360084
pmcid: 4197765
Prochnow N, Abdulazim A, Kurtenbach S et al (2012) Pannexin1 Stabilizes Synaptic Plasticity and Is Needed for Learning. PLoS ONE 7:51767. https://doi.org/10.1371/JOURNAL.PONE.0051767
doi: 10.1371/JOURNAL.PONE.0051767
Novielli-Kuntz NM, Jelen M, Barr K, et al (2019) Ablation of both Cx40 and Panx1 results in similar cardiovascular phenotypes exhibited in Cx40 knockout mice. Biosci Rep 39:. https://doi.org/10.1042/BSR20182350/110936
Scemes E, Velíšková J (2019) Exciting and not so exciting roles of pannexins. Neurosci Lett 695:25. https://doi.org/10.1016/J.NEULET.2017.03.010
doi: 10.1016/J.NEULET.2017.03.010
pubmed: 28284836
Freitas-Andrade M, Bechberger JF, MacVicar BA, et al (2017) Pannexin 1 knockout and blockade reduces ischemic stroke injury in female but not in male mice. Oncotarget 8:36973–36983. https://doi.org/10.18632/ONCOTARGET.16937
Li S, Zang Z, He J, et al (2016) Expression of pannexin 1 and 2 in cortical lesions from intractable epilepsy patients with focal cortical dysplasia. Oncotarget 8:6883–6895. https://doi.org/10.18632/ONCOTARGET.14317
Yin F, Zheng P qing, Zhao L qi, et al (2021) Caspase-11 promotes NLRP3 inflammasome activation via the cleavage of pannexin1 in acute kidney disease. Acta Pharmacologica Sinica 2021 43:1 43:86–95. https://doi.org/10.1038/s41401-021-00619-2
Chen KW, Demarco B, Broz P (2020) Pannexin-1 promotes NLRP3 activation during apoptosis but is dispensable for canonical or noncanonical inflammasome activation. Eur J Immunol 50:170–177. https://doi.org/10.1002/EJI.201948254
doi: 10.1002/EJI.201948254
pubmed: 31411729
Makarenkova HP, Shestopalov VI (2014) The role of pannexin hemichannels in inflammation and regeneration. Front Physiol 5 FEB: https://doi.org/10.3389/FPHYS.2014.00063
Silverman WR, de Rivero Vaccari JP, Locovei S et al (2009) The Pannexin 1 Channel Activates the Inflammasome in Neurons and Astrocytes. J Biol Chem 284:18143. https://doi.org/10.1074/JBC.M109.004804
doi: 10.1074/JBC.M109.004804
pubmed: 19416975
pmcid: 2709345
Südkamp N, Shchyglo O, Manahan-Vaughan D (2021) Absence of Pannexin 1 Stabilizes Hippocampal Excitability After Intracerebral Treatment With Aβ (1–42) and Prevents LTP Deficits in Middle-Aged Mice. Front Aging Neurosci 13:100. https://doi.org/10.3389/FNAGI.2021.591735/BIBTEX
doi: 10.3389/FNAGI.2021.591735/BIBTEX
Stewart MKG, Plante I, Penuela S, Laird DW (2016) Loss of Panx1 Impairs Mammary Gland Development at Lactation: Implications for Breast Tumorigenesis. PLoS ONE 11:e0154162. https://doi.org/10.1371/JOURNAL.PONE.0154162
doi: 10.1371/JOURNAL.PONE.0154162
pubmed: 27099931
pmcid: 4839729