nach oben

Neurological Sciences

Erschienen in:

01.10.2012 | Original Article

Ginsenoside-Rd attenuates TRPM7 and ASIC1a but promotes ASIC2a expression in rats after focal cerebral ischemia

verfasst von: Yunxia Zhang, Linfu Zhou, Xiao Zhang, Jiuxu Bai, Ming Shi, Gang Zhao

Erschienen in: Neurological Sciences | Ausgabe 5/2012

Einloggen, um Zugang zu erhalten

Abstract

Our previous studies have showed that ginsenoside (GS)-Rd, a mono-compound isolated from traditional Chinese herb panax ginseng, has the neuroprotective effects following ischemic stroke. However, the underlying mechanisms are still largely unknown. Our latest study showed that GS-Rd could block calcium influx in cultured cortical neurons after excitotoxic injury, indicating that GS-Rd may act on cation channels. To explore this possibility, in this study, we used a rat middle cerebral artery occlusion (MCAO) model to examine the effects of GS-Rd on the expression of non-selective cation channels, including transient receptor potential melastatin (TRPM) and acid sensing ion channels (ASIC), and cation channels, including N-methyl-d-aspartate (NMDA) receptors, which all play essential roles in ischemic stroke. Our results showed that both TRPM and ASIC channels were expressed in the brain. At 24 h following MCAO insult, mRNA and protein expression levels of TRPM7, ASIC1a and ASIC2a were significantly increased. Pretreatment of 10 mg/kg GS-Rd attenuated MCAO-induced expression of TRPM7 and ASIC1a but promoted that of ASIC2a. In contrast, GS-Rd had no significant effects on the expression of NMDA receptors. Thus, our results suggest that GS-Rd neuroprotection following cerebral ischemia may be at least due to its effects on the expression of TRPM7, ASIC1a and ASIC2a.

Yokozawa T, Dong E (2001) Role of ginsenoside-Rd in cisplatin-induced renal injury: special reference to DNA fragmentation. Nephron 89(4):433–438. doi:10.1159/000046116 PubMedCrossRef

Yokozawa T, Liu ZW, Dong E (1998) A study of ginsenoside-Rd in a renal ischemia-reperfusion model. Nephron 78(2):201–206. doi:10.1159/000044911 PubMedCrossRef

Yokozawa T, Satoh A, Cho EJ (2004) Ginsenoside-Rd attenuates oxidative damage related to aging in senescence-accelerated mice. J Pharm Pharmacol 56(1):107–113. doi:10.1211/0022357022449 PubMedCrossRef

Ye R, Han J, Kong X, Zhao L, Cao R, Rao Z, Zhao G (2008) Protective effects of ginsenoside Rd on PC12 cells against hydrogen peroxide. Biol Pharm Bull 31(10):1923–1927. doi:10.1248/bpb.31.1923 PubMedCrossRef

Ye R, Li N, Han J, Kong X, Cao R, Rao Z, Zhao G (2009) Neuroprotective effects of ginsenoside Rd against oxygen-glucose deprivation in cultured hippocampal neurons. Neurosci Res 64(3):306–310. doi:10.1016/j.neures.2009.03.016 PubMedCrossRef

Li N, Liu B, Dluzen DE, Jin Y (2007) Protective effects of ginsenoside Rg2 against glutamate-induced neurotoxicity in PC12 cells. J Ethnopharmacol 111(3):458–463. doi:10.1016/j.jep.2006.12.015 PubMedCrossRef

Wu J, Jeong HK, Bulin SE, Kwon SW, Park JH, Bezprozvanny I (2009) Ginsenosides protect striatal neurons in a cellular model of Huntington’s disease. J Neurosci Res 87(8):1904–1912. doi:10.1002/jnr.22017 PubMedCrossRef

Ye R, Zhang X, Kong X, Han J, Yang Q, Zhang Y, Chen Y, Li P, Liu J, Shi M, Xiong L, Zhao G (2011) Ginsenoside Rd attenuates mitochondrial dysfunction and sequential apoptosis after transient focal ischemia. Neuroscience 178:169–180. doi:10.1016/j.neuroscience.2011.01.007 PubMedCrossRef

Ye R, Yang Q, Kong X, Han J, Zhang X, Zhang Y, Li P, Liu J, Shi M, Xiong L, Zhao G (2011) Ginsenoside Rd attenuates early oxidative damage and sequential inflammatory response after transient focal ischemia in rats. Neurochem Int 58(3):391–398. doi:10.1016/j.neuint.2010.12.015 PubMedCrossRef

10.

Liu X, Xia J, Wang L, Song Y, Yang J, Yan Y, Ren H, Zhao G (2009) Efficacy and safety of ginsenoside-Rd for acute ischaemic stroke: a randomized, double-blind, placebo-controlled, phase II multicenter trial. Eur J Neurol 16(5):569–575. doi:10.1111/j.1468-1331.2009.02534.x PubMedCrossRef

11.

Zhang C, Du F, Shi M, Ye R, Cheng H, Han J, Ma L, Cao R, Rao Z, Zhao G (2011) Ginsenoside Rd protects neurons against glutamate-induced excitotoxicity by inhibiting Ca(2+) influx. Cell Mol Neurobiol. doi:10.1007/s10571-011-9742-x

12.

Davis SM, Albers GW, Diener HC, Lees KR, Norris J (1997) Termination of acute stroke studies involving selfotel treatment. Lancet 349(9044):32. doi:10.1016/S0140-6736(05)62166-6 PubMedCrossRef

13.

Davis SM, Lees KR, Albers GW, Diener HC, Markabi S, Karlsson G, Norris J (2000) Selfotel in acute ischemic stroke: possible neurotoxic effects of an NMDA antagonist. Stroke 31(2):347–354. doi:10.1161/01.STR.31.2.347 PubMedCrossRef

14.

Lees KR, Asplund K, Carolei A, Davis SM, Diener HC, Kaste M, Orgogozo JM, Whitehead J (2000) Glycine antagonist (gavestinel) in neuroprotection (GAIN International) in patients with acute stroke: a randomised controlled trial. Lancet 355(9219):1949–1954. doi:10.1016/S0140-6736(00)02326-6 PubMedCrossRef

15.

Aarts M, Iihara K, Wei WL, Xiong ZG, Arundine M, Cerwinski W, MacDonald JF, Tymianski M (2003) A key role for TRPM7 channels in anoxic neuronal death. Cell 115(7):863–877. doi:10.1016/S0092-8674(03)01017-1 PubMedCrossRef

16.

Sun HS, Jackson MF, Martin LJ, Jansen K, Teves L, Cui H, Kiyonaka S, Mori Y, Jones M, Forder JP, Golde TE, Orser BA, Macdonald JF, Tymianski M (2009) Suppression of hippocampal TRPM7 protein prevents delayed neuronal death in brain ischemia. Nat Neurosci 12(10):1300–1307. doi:10.1038/nn.2395 PubMedCrossRef

17.

Fonfria E, Marshall IC, Benham CD, Boyfield I, Brown JD, Hill K, Hughes JP, Skaper SD, McNulty S (2004) TRPM2 channel opening in response to oxidative stress is dependent on activation of poly(ADP-ribose) polymerase. Br J Pharmacol 143(1):186–192. doi:10.1038/sj.bjp.0705914 PubMedCrossRef

18.

Hara Y, Wakamori M, Ishii M, Maeno E, Nishida M, Yoshida T, Yamada H, Shimizu S, Mori E, Kudoh J, Shimizu N, Kurose H, Okada Y, Imoto K, Mori Y (2002) LTRPC2 Ca²⁺-permeable channel activated by changes in redox status confers susceptibility to cell death. Mol Cell 9(1):163–173. doi:10.1016/S1097-2765(01)00438-5 PubMedCrossRef

19.

Xiong ZG, Chu XP, Simon RP (2006) Ca²⁺-permeable acid-sensing ion channels and ischemic brain injury. J Membr Biol 209(1):59–68. doi:10.1007/s00232-005-0840-x PubMedCrossRef

20.

Xiong ZG, Zhu XM, Chu XP, Minami M, Hey J, Wei WL, MacDonald JF, Wemmie JA, Price MP, Welsh MJ, Simon RP (2004) Neuroprotection in ischemia: blocking calcium-permeable acid-sensing ion channels. Cell 118(6):687–698. doi:10.1016/j.cell.2004.08.026 PubMedCrossRef

21.

Johnson MB, Jin K, Minami M, Chen D, Simon RP (2001) Global ischemia induces expression of acid-sensing ion channel 2a in rat brain. J Cereb Blood Flow Metab 21(6):734–740. doi:10.1097/00004647-200106000-00011 PubMedCrossRef

22.

Morin C, Zini R, Simon N, Tillement JP (2002) Dehydroepiandrosterone and alpha-estradiol limit the functional alterations of rat brain mitochondria submitted to different experimental stresses. Neuroscience 115(2):415–424. doi:10.1016/S0306-4522(02)00416-5 PubMedCrossRef

23.

Sutherland BA, Shaw OM, Clarkson AN, Jackson DN, Sammut IA, Appleton I (2005) Neuroprotective effects of (−)-epigallocatechin gallate following hypoxia-ischemia-induced brain damage: novel mechanisms of action. FASEB J 19(2):258–260. doi:10.1096/fj.04-2806fje PubMed

24.

Ye R, Kong X, Yang Q, Zhang Y, Han J, Li P, Xiong L, Zhao G (2011) Ginsenoside Rd in experimental stroke: superior neuroprotective efficacy with a wide therapeutic window. Neurotherapeutics 8(3):515–525. doi:10.1007/s13311-011-0051-3 PubMedCrossRef

25.

Xiong ZG, Pignataro G, Li M, Chang SY, Simon RP (2008) Acid-sensing ion channels (ASICs) as pharmacological targets for neurodegenerative diseases. Curr Opin Pharmacol 8(1):25–32. doi:10.1016/j.coph.2007.09.001 PubMedCrossRef

26.

Besancon E, Guo S, Lok J, Tymianski M, Lo EH (2008) Beyond NMDA and AMPA glutamate receptors: emerging mechanisms for ionic imbalance and cell death in stroke. Trends Pharmacol Sci 29(5):268–275. doi:10.1016/j.tips.2008.02.003 PubMedCrossRef

27.

Simard JM, Tarasov KV, Gerzanich V (2007) Non-selective cation channels, transient receptor potential channels and ischemic stroke. Biochim Biophys Acta 1772(8):947–957. doi:10.1016/j.bbadis.2007.03.004 PubMedCrossRef

28.

Jiang H, Tian SL, Zeng Y, Li LL, Shi J (2008) TrkA pathway(s) is involved in regulation of TRPM7 expression in hippocampal neurons subjected to ischemic-reperfusion and oxygen-glucose deprivation. Brain Res Bull 76(1–2):124–130. doi:10.1016/j.brainresbull.2008.01.013 PubMedCrossRef

29.

Fonfria E, Murdock PR, Cusdin FS, Benham CD, Kelsell RE, McNulty S (2006) Tissue distribution profiles of the human TRPM cation channel family. J Recept Signal Transduct Res 26(3):159–178. doi:10.1080/10799890600637506 PubMedCrossRef

30.

Fonfria E, Mattei C, Hill K, Brown JT, Randall A, Benham CD, Skaper SD, Campbell CA, Crook B, Murdock PR, Wilson JM, Maurio FP, Owen DE, Tilling PL, McNulty S (2006) TRPM2 is elevated in the tMCAO stroke model, transcriptionally regulated, and functionally expressed in C13 microglia. J Recept Signal Transduct Res 26(3):179–198. doi:10.1080/10799890600637522 PubMedCrossRef

31.

Waldmann R, Champigny G, Bassilana F, Heurteaux C, Lazdunski M (1997) A proton-gated cation channel involved in acid-sensing. Nature 386(6621):173–177. doi:10.1038/386173a0 PubMedCrossRef

32.

Shen L, Han JZ, Li C, Yue SJ, Liu Y, Qin XQ, Liu HJ, Luo ZQ (2007) Protective effect of ginsenoside Rg1 on glutamate-induced lung injury. Acta Pharmacol Sin 28(3):392–397. doi:10.1111/j.1745-7254.2007.00511.x PubMedCrossRef

33.

Kim S, Ahn K, Oh TH, Nah SY, Rhim H (2002) Inhibitory effect of ginsenosides on NMDA receptor-mediated signals in rat hippocampal neurons. Biochem Biophys Res Commun 296(2):247–254. doi:10.1016/S0006-291X(02)00870-7 PubMedCrossRef

34.

Kim S, Kim T, Ahn K, Park WK, Nah SY, Rhim H (2004) Ginsenoside Rg3 antagonizes NMDA receptors through a glycine modulatory site in rat cultured hippocampal neurons. Biochem Biophys Res Commun 323(2):416–424. doi:10.1016/j.bbrc.2004.08.106 PubMedCrossRef

35.

Lee E, Kim S, Chung KC, Choo MK, Kim DH, Nam G, Rhim H (2006) 20(S)-ginsenoside Rh2, a newly identified active ingredient of ginseng, inhibits NMDA receptors in cultured rat hippocampal neurons. Eur J Pharmacol 536(1–2):69–77. doi:10.1016/j.ejphar.2006.02.038 PubMedCrossRef

Titel: Ginsenoside-Rd attenuates TRPM7 and ASIC1a but promotes ASIC2a expression in rats after focal cerebral ischemia
verfasst von: Yunxia Zhang
Linfu Zhou
Xiao Zhang
Jiuxu Bai
Ming Shi
Gang Zhao
Publikationsdatum: 01.10.2012
Verlag: Springer Milan
Erschienen in: Neurological Sciences / Ausgabe 5/2012
Print ISSN: 1590-1874
Elektronische ISSN: 1590-3478
DOI: https://doi.org/10.1007/s10072-011-0916-6

Leitlinien kompakt für die Neurologie

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Neurologie

Nicht Creutzfeldt Jakob, sondern Abführtee-Vergiftung

29.05.2024 Hyponatriämie Nachrichten

Eine ältere Frau trinkt regelmäßig Sennesblättertee gegen ihre Verstopfung. Der scheint plötzlich gut zu wirken. Auf Durchfall und Erbrechen folgt allerdings eine Hyponatriämie. Nach deren Korrektur kommt es plötzlich zu progredienten Kognitions- und Verhaltensstörungen.

Schutz der Synapsen bei Alzheimer

29.05.2024 Morbus Alzheimer Nachrichten

Mit einem Neurotrophin-Rezeptor-Modulator lässt sich möglicherweise eine bestehende Alzheimerdemenz etwas abschwächen: Erste Phase-2-Daten deuten auf einen verbesserten Synapsenschutz.

Sozialer Aufstieg verringert Demenzgefahr

24.05.2024 Demenz Nachrichten

Ein hohes soziales Niveau ist mit die beste Versicherung gegen eine Demenz. Noch geringer ist das Demenzrisiko für Menschen, die sozial aufsteigen: Sie gewinnen fast zwei demenzfreie Lebensjahre. Umgekehrt steigt die Demenzgefahr beim sozialen Abstieg.

Hirnblutung unter DOAK und VKA ähnlich bedrohlich

17.05.2024 Direkte orale Antikoagulanzien Nachrichten

Kommt es zu einer nichttraumatischen Hirnblutung, spielt es keine große Rolle, ob die Betroffenen zuvor direkt wirksame orale Antikoagulanzien oder Marcumar bekommen haben: Die Prognose ist ähnlich schlecht.

Update Neurologie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Live-Webinar "Urologie und Sexualmedizin in der Praxis"

Springer Medizin

Abstract

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 5/2012

Association of estrogen receptor β gene polymorphisms with vascular dementia in women

Unilateral headache with bilateral internal ophthalmoplegia

Do ACE (rs4646994) and αADDUCIN (rs4961) gene polymorphisms predict the recurrence of hypertensive intracerebral hemorrhage?

CSF metabolites in the differential diagnosis of Alzheimer’s disease from frontal variant of frontotemporal dementia

Apogeotropic central positional nystagmus as a sole sign of nodular infarction