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Thiacremonone Potentiates Anti-Oxidant Effects to Improve Memory Dysfunction in an APP/PS1 Transgenic Mice Model

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Abstract

Alzheimer’s disease (AD) is pathologically characterized by excessive accumulation of amyloid-beta (Aβ) peptide. Evidence suggests that amyloid accumulation can be caused by oxidative stress and inflammatory responses. In this study, we examined neuroprotective effects of thiacremonone, an anti-oxidant and anti-inflammatory compound isolated from garlic. Treatment of thiacremonone significantly attenuated cognitive impairments in amyloid precursor protein (APP)/presenilin 1 (PS1) double-mutant transgenic mice. In addition, activation of nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) and extracellular signal-regulated kinase (ERK) pathways in the brain was potently inhibited by thiacremonone. We also observed that thiacremonone significantly inhibited activation of NF-κB and ERK pathways induced by H2O2 and Aβ1–42 in embryonic neuronal cells. Furthermore, thiacremonone augmented peroxiredoxin 6 (PRDX6) expression in vivo and in vitro associated with reduced oxidative stress of macromolecules such as protein and lipids. This study indicates that thiacremonone might exert memory improvement via stimulating anti-oxidant system. These multiple properties could attenuate Aβ accumulation and oxidative stress in Alzheimer’s brains. Thus, these results suggest that thiacremonone might be useful to intervene development or progression of neurodegeneration in AD.

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Acknowledgments

This work was supported by the National Research Foundation of Korea (NRF) grant funded by the Korean government (MSIP) (2011-0029480,2012R1A5A2051384) and by the Ministry of Trad, Industry & Energy (MOTIE, 1415139249) through the fostering project of Osong Academy-Industry Convergence (BIAO).

Conflict of Interest

The authors declare no conflicts of interest. All of the experimental procedures were approved by the Animal Care and Use Committee (IACUC) of the Chungbuk National University (approval number: CBNUA-144-1001-01).

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Authors and Affiliations

  1. Department of Maxillofacial Tissue Regeneration, School of Dentistry and Research Center for Tooth & Periodontal Regeneration (MRC), Kyung Hee University, 1 Heogi-dong, Dongdaemun-gu, Seoul, 130-701, Republic of Korea

    Hyung-Mun Yun, Kyung-Ran Park & Eun-Cheol Kim

  2. College of Pharmacy and Medical Research Center, Chungbuk National University, 12 Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, Korea

    Peng Jin, JaeRyun Hwang, Jea-Kyung Jung, Ki-Wan Oh, Bang Yeon Hwang, Sang Bae Han & Jin Tae Hong

  3. College of Agriculture, Life and Environments Sciences, Chungbuk National University, 12, Gaesin-dong, Heungduk-gu, Cheongju, Chungbuk, 361-763, Korea

    Heon-Sang Jeong

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  1. Hyung-Mun Yun
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Correspondence to Jin Tae Hong.

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Yun, HM., Jin, P., Park, KR. et al. Thiacremonone Potentiates Anti-Oxidant Effects to Improve Memory Dysfunction in an APP/PS1 Transgenic Mice Model. Mol Neurobiol 53, 2409–2420 (2016). https://doi.org/10.1007/s12035-015-9208-0

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