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Mol Med Rep. 2013 Jan;7(1):154-8. doi: 10.3892/mmr.2012.1135. Epub 2012 Oct 19.

Hirsutine, an indole alkaloid of Uncaria rhynchophylla, inhibits inflammation-mediated neurotoxicity and microglial activation.

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1
Department of Cardiovascular and Neurologic Diseases (Stroke Center), Hospital of Oriental Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea.

Abstract

Chronic microglial activation endangers neuronal survival through the release of various pro-inflammatory and neurotoxic factors. As such, negative regulators of microglial activation have been considered as potential therapeutic candidates to reduce the risk of neurodegeneration associated with inflammation. Uncaria rhynchophylla (U. rhynchophylla) is a traditional oriental herb that has been used for treatment of disorders of the cardiovascular and central nervous systems. Hirsutine (HS), one of the major indole alkaloids of U. rhynchophylla, has demonstrated neuroprotective potential. The aim of the present study was to examine the efficacy of HS in the repression of inflammation-induced neurotoxicity and microglial cell activation. In organotypic hippocampal slice cultures, HS blocked lipopolysaccharide (LPS)-related hippocampal cell death and production of nitric oxide (NO), prostaglandin (PG) E2 and interleukin-1β. HS was demonstrated to effectively inhibit LPS-induced NO release from cultured rat brain microglia. The compound reduced the LPS-stimulated production of PGE2 and intracellular reactive oxygen species. HS significantly decreased LPS-induced phosphorylation of the mitogen-activated protein kinases and Akt signaling proteins. In conclusion, HS reduces the production of various neurotoxic factors in activated microglial cells and possesses neuroprotective activity in a model of inflammation-induced neurotoxicity.

PMID:
23117160
DOI:
10.3892/mmr.2012.1135
[Indexed for MEDLINE]

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