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. 2018 Mar 14;16(3):94.
doi: 10.3390/md16030094.

Anti-BACE1 and Antimicrobial Activities of Steroidal Compounds Isolated from Marine Urechis unicinctus

Yong-Zhe Zhu  1 , Jing-Wen Liu  2 , Xue Wang  3 , In-Hong Jeong  4 , Young-Joon Ahn  5 , Chuan-Jie Zhang  6
Affiliations

Anti-BACE1 and Antimicrobial Activities of Steroidal Compounds Isolated from Marine Urechis unicinctus

Yong-Zhe Zhu et al. Mar Drugs. .

Abstract

The human β-site amyloid cleaving enzyme (BACE1) has been considered as an effective drug target for treatment of Alzheimer's disease (AD). In this study, Urechis unicinctus (U. unicinctus), which is a Far East specialty food known as innkeeper worm, ethanol extract was studied by bioassay-directed fractionation and isolation to examine its potential β-site amyloid cleaving enzyme inhibitory and antimicrobial activity. The following compounds were characterized: hecogenin, cholest-4-en-3-one, cholesta-4,6-dien-3-ol, and hurgadacin. These compounds were identified by their mass spectrometry, ¹H, and 13C NMR spectral data, comparing those data with NIST/EPA/NIH Mass spectral database (NIST11) and published values. Hecogenin and cholest-4-en-3-one showed significant inhibitory activity against BACE1 with EC50 values of 116.3 and 390.6 µM, respectively. Cholesta-4,6-dien-3-ol and hurgadacin showed broad spectrum antimicrobial activity, particularly strongly against Escherichia coli (E. coli), Salmonella enterica (S. enterica), Pasteurella multocida (P. multocida), and Physalospora piricola (P. piricola), with minimal inhibitory concentration (MIC) ranging from 0.46 to 0.94 mg/mL. This is the first report regarding those four known compounds that were isolated from U. unicinctus and their anti-BACE1 and antimicrobial activity, highlighting the fact that known natural compounds may be a critical source of new medicine leads. These findings provide scientific evidence for potential application of those bioactive compounds for the development of AD drugs and antimicrobial agents.

Keywords: Alzheimer’s disease; BACE1; Urechis unicinctus; antimicrobial activity; bioassay-directed isolation; marine bioactive.

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Conflict of interest statement

The authors declare no competing financial interest.

Figures

Figure 1
Figure 1
The chemical structures of isolated compounds from chloroform (A–C) and ethyl acetate (D) fractions of U. unicinctus.
Figure 2
Figure 2
Bioassay-directed isolation scheme of BACE1 inhibitory and antimicrobial activity compounds from U. unicinctus.
See this image and copyright information in PMC

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