Dataset Information

A Chinese Herbal Formula, Gengnianchun, Ameliorates ?-Amyloid Peptide Toxicity in a Caenorhabditis elegans Model of Alzheimer's Disease.

ABSTRACT: Alzheimer's disease (AD) is an age-related neurodegenerative disorder, and the few drugs that are currently available only treat the symptoms. Traditional medicine or phytotherapy has been shown to protect against AD. In our previous studies, Gengnianchun (GNC), a traditional Chinese medicine formula with a prolongevity effect, protected against A?-induced cytotoxicity in pheochromocytoma cells (PC-12 cells) and hippocampal cells. Here, we investigated the effects and possible mechanisms by which GNC protected against A? toxicity using transgenic Caenorhabditis elegans CL4176. Our results showed that GNC effectively delayed the A? toxicity-triggered body paralysis of CL4176 worms. GNC decreased A? by reducing A? mRNA levels. Moreover, GNC significantly reduced reactive oxygen species in the AD model worms compared with the controls. In addition, GNC upregulated the daf-16, sod-3, hsp-16.2 genes, and enhanced DAF-16 translocation from the cytoplasm to the nuclei under oxidative stress conditions. GNC treatment of C. elegans strains lacking DAF-16 did not affect the paralysis phenotype. Taken together, these findings suggest that GNC could protect against A?-induced toxicity via the DAF-16 pathway in C. elegans. Further studies are required to analyze its effectiveness in more complex animals.

SUBMITTER: Meng F

PROVIDER: S-EPMC5660795 | biostudies-literature | 2017

REPOSITORIES: biostudies-literature

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Publications

A Chinese Herbal Formula, Gengnianchun, Ameliorates β-Amyloid Peptide Toxicity in a Caenorhabditis elegans Model of Alzheimer's Disease.

Meng Fanhui F Li Jun J Rao Yanqiu Y Wang Wenjun W Fu Yan Y

Evidence-based complementary and alternative medicine : eCAM 20171011

Alzheimer's disease (AD) is an age-related neurodegenerative disorder, and the few drugs that are currently available only treat the symptoms. Traditional medicine or phytotherapy has been shown to protect against AD. In our previous studies, Gengnianchun (GNC), a traditional Chinese medicine formula with a prolongevity effect, protected against Aβ-induced cytotoxicity in pheochromocytoma cells (PC-12 cells) and hippocampal cells. Here, we investigated the effects and possible mechanisms ...[more]

PMID: 29234427

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Project description:Liuwei Dihuang (LWDH), a classic Chinese medicinal formula, has been used to improve or restore declined functions related to aging and geriatric diseases, such as impaired mobility, vision, hearing, cognition and memory. Here, we report on the effect and possible mechanisms of LWDH mediated protection of ?-amyloid (A?) induced paralysis in Caenorhabditis elegans using ethanol extract (LWDH-EE) and water extract (LWDH-WE). Chemical profiling and quantitative analysis revealed the presence of different levels of bioactive components in these extracts. LWDH-WE was rich in polar components such as monosaccharide dimers and trimers, whereas LWDH-EE was enriched in terms of phenolic compounds such as gallic acid and paeonol. In vitro studies revealed higher DPPH radical scavenging activity for LWDH-EE as compared to that found for LWDH-WE. Neither LWDH-EE nor LWDH-WE were effective in inhibiting aggregation of A? in vitro. By contrast, LWDH-EE effectively delayed A? induced paralysis in the transgenic C. elegans (CL4176) model which expresses human A?1-42. Western blot revealed no treatment induced reduction in A? accumulation in CL4176 although a significant reduction was observed at an early stage with respect to ?-amyloid deposition in C. elegans strain CL2006 which constitutively expresses human A?1-42. In addition, LWDH-EE reduced in vivo reactive oxygen species (ROS) in C. elegans (CL4176) that correlated with increased survival of LWDH-EE treated N2 worms under juglone-induced oxidative stress. Analysis with GFP reporter strain TJ375 revealed increased expression of hsp16.2::GFP after thermal stress whereas a minute induction was observed for sod3::GFP. Quantitative gene expression analysis revealed that LWDH-EE repressed the expression of amy1 in CL4176 while up-regulating hsp16.2 induced by elevating temperature. Taken together, these results suggest that LWDH extracts, particularly LWDH-EE, alleviated ?-amyloid induced toxicity, in part, through up-regulation of heat shock protein, antioxidant activity and reduced ROS in C. elegans.

Dataset Information

A Chinese Herbal Formula, Gengnianchun, Ameliorates ?-Amyloid Peptide Toxicity in a Caenorhabditis elegans Model of Alzheimer's Disease.

Publications

A Chinese Herbal Formula, Gengnianchun, Ameliorates <i>β</i>-Amyloid Peptide Toxicity in a <i>Caenorhabditis elegans</i> Model of Alzheimer's Disease.

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