Hexane extract from Uncaria sinensis exhibits anti-apoptotic properties against glutamate-induced neurotoxicity in primary cultured cortical neurons

Jang,Ji-Yeon; Kim,Ha-Neui; Kim,Yu-Ri; Hong,Jin-Woo; Choi,Young-Whan; Choi,Yung-Hyun; Shin,Hwa-Kyoung; Choi,Byung-Tae

doi:10.3892/ijmm.2012.1134

Hexane extract from Uncaria sinensis exhibits anti-apoptotic properties against glutamate-induced neurotoxicity in primary cultured cortical neurons

Authors:
- Ji-Yeon Jang
- Ha-Neui Kim
- Yu-Ri Kim
- Jin-Woo Hong
- Young-Whan Choi
- Yung-Hyun Choi
- Hwa-Kyoung Shin
- Byung-Tae Choi
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Affiliations: Division of Meridian and Structural Medicine, Pusan National University, Yangsan 626-870, Republic of Korea, Division of Clinical Medicine I, School of Korean Medicine, Pusan National University, Yangsan 626-870, Republic of Korea, Department of Horticultural Bioscience, College of Natural Resources and Life Science, Pusan National University, Miryang 626-706, Republic of Korea, Department of Biochemistry, College of Oriental Medicine, Dongeui University, Busan 614-052, Republic of Korea
Published online on: September 19, 2012 https://doi.org/10.3892/ijmm.2012.1134
Pages: 1465-1472

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Abstract

We explored the neuroprotective effects of a hexane extract from Uncaria sinensis (HEUS) against glutamate-induced toxicity focusing on its anti-apoptotic mechanism in primary cultured cortical neurons. Pretreatment with HEUS resulted in significantly reduced glutamate-induced toxicity in a dose-dependent manner with a decrease in the release of lactate dehydrogenase. Morphological assay and flow cytometry were performed for determination of the type of cell death; according to the results, treatment with HEUS resulted in a significant reduction of glutamate-induced apoptotic cell death. We examined the anti-apoptotic mechanism of HEUS; treatment with HEUS resulted in markedly decreased expression of death receptor (DR)4, which was induced by glutamate stimulation. In contrast, treatment with HEUS resulted in significantly enhanced levels of expression of glutamate-attenuated XIAP and Bcl-2, as well as marked blockade of glutamate-induced Bid cleavage, which inhibits both extrinsic and intrinsic apoptosis pathways. In addition, pretreatment with HEUS resulted in almost complete blockade of glutamate-induced activation of caspases-8, -9 and -3, as well as cleavage of poly (ADP-ribose) polymerase. These findings suggest that the neuroprotective effects of HEUS against glutamate-induced toxicity occur via inhibition of DR4 and expression of anti-apoptotic proteins XIAP and Bcl-2 resulting in effective abrogation of the activation of caspase cascades and promotion of cell survival.

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