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

Jung,Hwan  Yong; Nam,Kyong  Nyon; Woo,Byung-Choel; Kim,Kyoo-Pil; Kim,Sung-Ok; Lee,Eunjoo  H.

doi:10.3892/mmr.2012.1135

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

Authors:
- Hwan Yong Jung
- Kyong Nyon Nam
- Byung-Choel Woo
- Kyoo-Pil Kim
- Sung-Ok Kim
- Eunjoo H. Lee
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Affiliations: Department of Cardiovascular and Neurologic Diseases (Stroke Center), Hospital of Oriental Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea, Graduate School of East‑West Medical Science, Kyung Hee University, Yongin-si 446-701, Republic of Korea, Department of Cardiovascular and Neurologic Diseases (Stroke Center), Hospital of Oriental Medicine, Kyung Hee University, Seoul 130-702, Republic of Korea, Department of Herbal Pharmacology, College of Oriental Medicine, Daegu Haany University, Daegu 706-060, Republic of Korea, Graduate School of East‑West Medical Science, Kyung Hee University, Yongin-si 446-701, Republic of Korea
Published online on: October 19, 2012 https://doi.org/10.3892/mmr.2012.1135
Pages: 154-158

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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.

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