Dataset Information

5-Hydroxycyclopenicillone Inhibits ?-Amyloid Oligomerization and Produces Anti-?-Amyloid Neuroprotective Effects In Vitro.

ABSTRACT: The oligomer of ?-amyloid (A?) is considered the main neurotoxin in Alzheimer's disease (AD). Therefore, the inhibition of the formation of A? oligomer could be a target for AD therapy. In this study, with the help of the dot blotting assay and transmission electronic microscopy, it was have discovered that 5-hydroxycyclopenicillone, a cyclopentenone recently isolated from a sponge-associated fungus, effectively reduced the formation of A? oligomer from A? peptide in vitro. Molecular dynamics simulations suggested hydrophobic interactions between 5-hydroxycyclopenicillone and A? peptide, which might prevent the conformational transition and oligomerization of A? peptide. Moreover, A? oligomer pre-incubated with 5-hydroxycyclopenicillone was less toxic when added to neuronal SH-SY5Y cells compared to the normal A? oligomer. Although 5-hydroxycyclopenicillone is not bioavailable in the brain in its current form, further modification or encapsulation of this chemical might improve the penetration of 5-hydroxycyclopenicillone into the brain. Based on the current findings and the anti-oxidative stress properties of 5-hydroxycyclopenicillone, it is suggested that 5-hydroxycyclopenicillone may have potential therapeutic efficacy in treating AD.

SUBMITTER: Zhao J

PROVIDER: S-EPMC6151400 | biostudies-literature | 2017 Oct

REPOSITORIES: biostudies-literature

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5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro.

Zhao Jiaying J Liu Fufeng F Huang Chunhui C Shentu Jieyi J Wang Minjun M Sun Chenkai C Chen Liping L Yan Sicheng S Fang Fang F Wang Yuanyuan Y Xu Shujun S Naman C Benjamin CB Wang Qinwen Q He Shan S Cui Wei W

Molecules (Basel, Switzerland) 20171001 10

The oligomer of β-amyloid (Aβ) is considered the main neurotoxin in Alzheimer's disease (AD). Therefore, the inhibition of the formation of Aβ oligomer could be a target for AD therapy. In this study, with the help of the dot blotting assay and transmission electronic microscopy, it was have discovered that 5-hydroxycyclopenicillone, a cyclopentenone recently isolated from a sponge-associated fungus, effectively reduced the formation of Aβ oligomer from Aβ peptide in vitro. Molecular dynamics si ...[more]

PMID: 28974023

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Project description:BackgroundNeuroinflammation and the presence of amyloid beta protein (Aβ) and neurofibrillary tangles are key pathologies in Alzheimer's disease (AD). As a potent anti-amyloid and anti-inflammatory natural polyphenol, curcumin (Cur) could be potential therapies for AD. Unfortunately, poor solubility, instability in physiological fluids, and low bioavailability limit its clinical utility. Recently, different lipid modifications in the formulae of Cur have been developed that would enhance its therapeutic potential. For example, we have reported greater permeability and neuroprotection with solid lipid curcumin particles (SLCP) than with natural Cur in an in vitro model of AD. In the present study, we compared the Aβ aggregation inhibition, anti-amyloid, anti-inflammatory responses of Cur and or SLCP in both in vitro and in vivo models of AD. One-year-old 5xFAD-and age-matched wild-type mice were given intraperitoneal injections of Cur or SLCP (50 mg/kg body weight) for 2- or 5-days. Levels of Aβ aggregation, including oligomers and fibril formation, were assessed by dot blot assay, while Aβ plaque load and neuronal morphology in the pre-frontal cortex (PFC) and hippocampus were assayed by immunolabeling with Aβ-specific antibody and cresyl violet staining, respectively. In addition, neuroinflammation was assessed the immunoreactivity (IR) of activated astrocytes (GFAP) and microglia (Iba-1) in different brain areas. Finally, comparisons of solubility and permeability of Cur and SLCP were made in cultured N2a cells and in primary hippocampal neurons derived from E16 pups of 5xFAD mice.ResultsWe observed that relative to Cur, SLCP was more permeable, labeled Aβ plaques more effectively, and produced a larger decrease in Aβ plaque loads in PFC and dentate gyrus (DG) of hippocampus. Similarly, relative to Cur, SLCP produced a larger decrease of pyknotic, or tangle-like, neurons in PFC, CA1, and CA3 areas of hippocampus after 5 days of treatment. Both Cur and or SLCP significantly reduced GFAP-IR and Iba-1-IR in PFC, in the striatum as well as CA1, CA3, DG, subicular complex of hippocampus, and the entorhinal cortex in the 5xFAD mice after 5 days of treatment.ConclusionsThe use of SLCP provides more anti-amyloid, anti-inflammatory, and neuroprotective outcomes than does Cur in the 5xFAD mouse model of AD.

Dataset Information

5-Hydroxycyclopenicillone Inhibits ?-Amyloid Oligomerization and Produces Anti-?-Amyloid Neuroprotective Effects In Vitro.

Publications

5-Hydroxycyclopenicillone Inhibits β-Amyloid Oligomerization and Produces Anti-β-Amyloid Neuroprotective Effects In Vitro.

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