Effects of curcuminoids identified in rhizomes of Curcuma longa on BACE-1 inhibitory and behavioral activity and lifespan of Alzheimer’s disease Drosophila models

BMC Complementary and Alternative Medicine

Young-Joon Ahn⁴  Hyung-Wook Kwon⁴  Moon Young Jung⁴  Young-Joon Kim²  Seong-Baek Lee³  Jun-Ran Kim⁴  Xue Wang¹ 

[1] Entomology Major, Department of Agriculture Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea;School of Life Sciences, Gwangju Insititute of Science and Technology, Gwangju 500-712, Republic of Korea;Cellumed Co. Ltd, Geumocheon-gu, Seoul 153-782, Republic of Korea;WCU Biomodulation Major, Department of Agricultural Biotechnology, Seoul National University, Seoul 151-921, Republic of Korea

关键词: Structure–activity relationship;    BACE-1;    Curcuminoids;    Curcuma longa;    Drosophila melanogaster;    Alzheimer’s disease;   

Others  :  1220235
DOI  :  10.1186/1472-6882-14-88

 received in 2013-08-14, accepted in 2014-02-25,  发布年份 2014

【 摘 要 】

Background

Alzheimer’s disease (AD) is the most common type of presenile and senile dementia. The human β-amyloid precursor cleavage enzyme (BACE-1) is a key enzyme responsible for amyloid plaque production, which implicates the progress and symptoms of AD. Here we assessed the anti-BACE-1 and behavioral activities of curcuminoids from rhizomes of Curcuma longa (Zingiberaceae), diarylalkyls curcumin (CCN), demethoxycurcumin (DMCCN), and bisdemethoxycurcumin (BDMCCN) against AD Drosophila melanogaster models.

Methods

Neuro-protective ability of the curcuminoids was assessed using Drosophila melanogaster model system overexpressing BACE-1 and its substrate APP in compound eyes and entire neurons. Feeding and climbing activity, lifespan, and morphostructural changes in fly eyes also were evaluated.

Results

BDMCCN has the strongest inhibitory activity toward BACE-1 with 17 μM IC₅₀, which was 20 and 13 times lower than those of CCN and DMCCN respectively. Overexpression of APP/BACE-1 resulted in the progressive and measurable defects in morphology of eyes and locomotion. Remarkably, supplementing diet with either 1 mM BDMCCN or 1 mM CCN rescued APP/BACE1-expressing flies and kept them from developing both morphological and behavioral defects. Our results suggest that structural characteristics, such as degrees of saturation, types of carbon skeleton and functional group, and hydrophobicity appear to play a role in determining inhibitory potency of curcuminoids on BACE-1.

Conclusion

Further studies will warrant possible applications of curcuminoids as therapeutic BACE-1 blockers.

【 授权许可】

   
2014 Wang et al.; licensee BioMed Central Ltd.

【 图 表 】

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