Plumbagin, a novel Nrf2/ARE activator, protects against cerebral ischemia

Tae Gen Son, Simonetta Camandola, Thiruma V. Arumugam, Roy G. Cutler, Richard S. Telljohann, Mohamed R. Mughal, Tyson A. Moore, Weiming Luo, Qian Sheng Yu, Delinda A. Johnson, Jeffrey A. Johnson, Nigel H. Greig, Mark P. Mattson

Research output: Contribution to journalArticle

Abstract

Many phytochemicals function as noxious agents that protect plants against insects and other damaging organisms. However, at subtoxic doses, the same phytochemicals may activate adaptive cellular stress response pathways that can protect cells against a variety of adverse conditions. We screened a panel of botanical pesticides using cultured human and rodent neuronal cell models, and identified plumbagin as a novel potent activator of the nuclear factor E2-related factor 2 (Nrf2)/antioxidant response element (ARE) pathway. In vitro, plumbagin increases nuclear localization and transcriptional activity of Nrf2, and induces the expression of the Nrf2/ARE-dependent genes, such as heme oxygenase 1 in human neuroblastoma cells. Plumbagin specifically activates the Nrf2/ARE pathway in primary mixed cultures from ARE-human placental alkaline phosphatase reporter mice. Exposure of neuroblastoma cells and primary cortical neurons to plumbagin provides protection against subsequent oxidative and metabolic insults. The neuroprotective effects of plumbagin are abolished by RNA interference-mediated knockdown of Nrf2 expression. In vivo, administration of plumbagin significantly reduces the amount of brain damage and ameliorates-associated neurological deficits in a mouse model of focal ischemic stroke. Our findings establish precedence for the identification and characterization of neuroprotective phytochemicals based upon their ability to activate adaptive cellular stress response pathways.

Original languageEnglish (US)
Pages (from-to)1316-1326
Number of pages11
JournalJournal of Neurochemistry
Volume112
Issue number5
DOIs
StatePublished - Mar 2010

Fingerprint

NF-E2-Related Factor 2
Antioxidant Response Elements
Brain Ischemia
Phytochemicals
Neuroblastoma
Heme Oxygenase-1
Neuroprotective Agents
RNA Interference
Pesticides
Neurons
Insects
plumbagin
Rodentia
Brain
Genes
Stroke
RNA

Keywords

  • Neuroprotection
  • Nrf2/ARE
  • Phytochemicals
  • Stroke

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Son, T. G., Camandola, S., Arumugam, T. V., Cutler, R. G., Telljohann, R. S., Mughal, M. R., ... Mattson, M. P. (2010). Plumbagin, a novel Nrf2/ARE activator, protects against cerebral ischemia. Journal of Neurochemistry, 112(5), 1316-1326. https://doi.org/10.1111/j.1471-4159.2009.06552.x

Plumbagin, a novel Nrf2/ARE activator, protects against cerebral ischemia. / Son, Tae Gen; Camandola, Simonetta; Arumugam, Thiruma V.; Cutler, Roy G.; Telljohann, Richard S.; Mughal, Mohamed R.; Moore, Tyson A.; Luo, Weiming; Yu, Qian Sheng; Johnson, Delinda A.; Johnson, Jeffrey A.; Greig, Nigel H.; Mattson, Mark P.

In: Journal of Neurochemistry, Vol. 112, No. 5, 03.2010, p. 1316-1326.

Research output: Contribution to journalArticle

Son, TG, Camandola, S, Arumugam, TV, Cutler, RG, Telljohann, RS, Mughal, MR, Moore, TA, Luo, W, Yu, QS, Johnson, DA, Johnson, JA, Greig, NH & Mattson, MP 2010, 'Plumbagin, a novel Nrf2/ARE activator, protects against cerebral ischemia', Journal of Neurochemistry, vol. 112, no. 5, pp. 1316-1326. https://doi.org/10.1111/j.1471-4159.2009.06552.x
Son TG, Camandola S, Arumugam TV, Cutler RG, Telljohann RS, Mughal MR et al. Plumbagin, a novel Nrf2/ARE activator, protects against cerebral ischemia. Journal of Neurochemistry. 2010 Mar;112(5):1316-1326. https://doi.org/10.1111/j.1471-4159.2009.06552.x
Son, Tae Gen ; Camandola, Simonetta ; Arumugam, Thiruma V. ; Cutler, Roy G. ; Telljohann, Richard S. ; Mughal, Mohamed R. ; Moore, Tyson A. ; Luo, Weiming ; Yu, Qian Sheng ; Johnson, Delinda A. ; Johnson, Jeffrey A. ; Greig, Nigel H. ; Mattson, Mark P. / Plumbagin, a novel Nrf2/ARE activator, protects against cerebral ischemia. In: Journal of Neurochemistry. 2010 ; Vol. 112, No. 5. pp. 1316-1326.
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