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Liuwei Dihuang (LWDH), a traditional Chinese medicinal formula, protects against ?-amyloid toxicity in transgenic Caenorhabditis elegans.

ABSTRACT: 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.

SUBMITTER: Sangha JS

PROVIDER: S-EPMC3431378 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Liuwei Dihuang (LWDH), a traditional Chinese medicinal formula, protects against β-amyloid toxicity in transgenic Caenorhabditis elegans.

Sangha Jatinder S JS Sun Xiaoli X Wally Owen S D OS Zhang Kaibin K Ji Xiuhong X Wang Zhimin Z Wang Yanwen Y Zidichouski Jeffrey J Prithiviraj Balakrishnan B Zhang Junzeng J

PloS one 20120830 8

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 β-amyloid (Aβ) induced paralysis in Caenorhabditis elegans using ethanol extract (LWDH-EE) and water extract (LWDH-WE). Chemical profiling and quantitative analysis revealed the presence of dif ...[more]

PMID: 22952840

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Project description:BackgroundVitiligo stands as a challenging skin disorder with limited treatment options available. LiuWei DiHuang formula (LDF), a renowned Traditional Chinese medicine, has exhibited promising results in treating vitiligo over an extended period. However, the precise underlying mechanism of its action remains elusive.MethodsEmploying a comprehensive network pharmacology approach, this study identified active compounds and their corresponding targets within LDF, while also pinpointing vitiligo-associated targets sourced from the TCMSP database, OMIM, DisGenNET, and Genecards. A network was established to illustrate the connections between active compounds and targets, alongside a protein-protein interaction network. Further analyses, encompassing Gene Ontology (GO) function and KEGG pathway enrichment, were conducted using the DAVID platform. Molecular docking simulations were performed utilizing AutoDockTools and AutoDockVina software. To validate the outcomes of the systematic pharmacological investigation, experiments were conducted using juvenile zebrafish.ResultsThe collective effort of the network pharmacology approach yielded a compilation of 41 compounds and 192 targets. Molecular docking simulations notably revealed the lowest binding energies for CAT-quercetin and CAT-Kaempferol interactions. The utilization of juvenile zebrafish experiments highlighted a significant increase in melanocyte count following methoxsalen and LDF treatment. Notably, LDF prominently augmented the expression levels of proteins related to melanogenesis. Additionally, LDF showcased the capacity to enhance CAT and SOD levels while concurrently reducing ROS and MDA activity. In contrast to the model group, substantial increases in protein and mRNA levels of Nrf2 and HO-1 were observed in response to LDF treatment (P < 0.05).ConclusionThrough a meticulous network pharmacology approach, this study successfully predicted active components and potential targets associated with LDF's application in vitiligo treatment. The therapeutic effectiveness of LDF against vitiligo is postulated to stem from its regulation of oxidative stress factors and the Nrf2/HO-1 pathway.

Dataset Information

Liuwei Dihuang (LWDH), a traditional Chinese medicinal formula, protects against ?-amyloid toxicity in transgenic Caenorhabditis elegans.

Publications

Liuwei Dihuang (LWDH), a traditional Chinese medicinal formula, protects against β-amyloid toxicity in transgenic Caenorhabditis elegans.

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