Anti-inflammatory effect of visnagin in lipopolysaccharide-stimulated BV-2 microglial cells

Lee, Jin-Koo; Jung, Jun‐Sub; Park, Sanghee; Park, Soo-Hyun; Sim, Yun-Beom; Kim, Seon-Mi; Ha, T. Van; Suh, Hwal

doi:10.1007/s12272-010-1117-1

Cited by 47 publications

(27 citation statements)

References 34 publications

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“…Khellin is a vasodilator and bronchodilator [12]. It has been implicated, along with its chemical relative visnagin, in the inhibition of nuclear factor κB [13]. It is an anti-inflammatory agent, and its mechanism of action is blocking the calcium channel in cells [11].…”

Section: Resultsmentioning

confidence: 99%

Morphological Effects of Natural Products on Schizosaccharomyces pombe Measured by Imaging Flow Cytometry

Heisler

Elvir

Barnouti

et al. 2014

Nat. Prod. Bioprospect.

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Gaining a full understanding of the mechanisms of action of natural products as therapeutic agents includes observing the effects of natural products on cellular morphology, because abnormal cellular morphology is an important aspect of cellular transformations that occur as part of disease states. In this study a set of natural products was examined in search of small molecules that influence the cylindrical morphology of fission yeast Schizosaccharomyces pombe. Imaging flow cytometry of large populations of S. pombe exposed to natural products captured cell images and revealed changes in mean length and aspect ratio of cells. Several natural products were found to alter S. pombe’s morphology relative to control, in terms of elongating cells, shrinking them, or making them more round. These results may facilitate future investigations into methods by which cells establish and maintain specific shapes.Graphical AbstractGaining a full understanding of the mechanisms of action of natural products as therapeutic agents includes observing the effects of natural products on cellular morphology, because abnormal cellular morphology is an important aspect of cellular transformations that occur as part of disease states. In this study a set of natural products was examined in search of small molecules that influence the cylindrical morphology of fission yeast Schizosaccharomyces pombe. Imaging flow cytometry of large populations of S. pombe exposed to natural products captured cell images and revealed changes in mean length and aspect ratio of cells. Several natural products were found to alter S. pombe’s morphology relative to control, in terms of elongating cells, shrinking them, or making them more round. These results may facilitate future investigations into methods by which cells establish and maintain specific shapes.

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Section: Resultsmentioning

confidence: 99%

Morphological Effects of Natural Products on Schizosaccharomyces pombe Measured by Imaging Flow Cytometry

Heisler

Elvir

Barnouti

et al. 2014

Nat. Prod. Bioprospect.

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“…It has been reported that VIS can protect kidney epithelial cells from damage by oxalate and protect neurons from kainic acid-induced apoptosis (22, 23). Furthermore, VIS has been shown to inhibit LPS-stimulated inflammation in a microglial cell line (24). Very little is known about the biological function and target of DPU.…”

Section: Discussionmentioning

confidence: 99%

Visnagin protects against doxorubicin-induced cardiomyopathy through modulation of mitochondrial malate dehydrogenase

et al. 2014

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Doxorubicin is a highly effective anti-cancer chemotherapy agent, but its usage is limited by its cardiotoxicity. To develop a drug that prevents the cardiac toxicity of doxorubicin while preserving its anti-tumor potency, we established a doxorubicin-induced cardiomyopathy model in zebrafish that recapitulated the cardiomyocyte apoptosis and contractility decline observed in patients. Using this model, we screened 3000 compounds and discovered that visnagin (VIS) and diphenylurea (DPU) rescue cardiac performance and circulatory defects caused by doxorubicin treatment in zebrafish. VIS and DPU reduced doxorubicin-induced apoptosis in cultured cardiomyocytes and in vivo in zebrafish and mouse hearts. Furthermore, VIS treatment improved cardiac contractility in doxorubicin-treated mice. Importantly, VIS and DPU caused no reduction in the chemotherapeutic efficacy of doxorubicin in several cultured tumor lines or in zebrafish and mouse xenograft models. Using affinity chromatography, we discovered that VIS binds to mitochondrial malate dehydrogenase (MDH2), one of the key enzymes in the tricarboxylic acid cycle. As with VIS, treatment with the MDH2 inhibitors mebendazole, thyroxine, and iodine prevented doxorubicin cardiotoxicity, as did treatment with malate itself, suggesting that modulation of MDH2 activity is responsible for VIS’s cardioprotective effects. Taken together, this study identified VIS and DPU as potent cardioprotective compounds and implicates MDH2 as a previously undescribed, druggable target for doxorubicin-induced cardiomyopathy.

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“…Both compounds exhibit vasodilatory activities due to their calcium channel blocking properties [15,16] and act in an anti-inflammatory manner by inhibiting AP-1 and NF-κB signaling [17]. Khellin has been extensively used by the pharmaceutical industry as basic raw material for the development of drugs such as the anti-asthmatic agent sodium cromoglycate or the widely used anti-arrhythmic drug amiodarone [18].…”

Section: Introductionmentioning

confidence: 99%

Khellin and Visnagin Differentially Modulate AHR Signaling and Downstream CYP1A Activity in Human Liver Cells

et al. 2013

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Khellin and visnagin are two furanochromones that can be frequently found in ethnomedical formulations in Asia and the Middle East. Both compounds possess anti-inflammatory and analgesic properties, therefore modern medicine uses these compounds or structurally related derivatives for treatment of vitiligo, bronchial asthma and renal colics. Despite their frequent usage, the potential toxic properties of visnagin and khellin are not well characterized up-to-now. Many natural compounds modulate the expression and activity of cytochrome P450 1A1 (CYP1A1), which is well-known to bioactivate pro-carcinogens. The expression of this enzyme is controlled by the aryl hydrocarbon receptor (AHR), a ligand-activated transcription factor and regulator of drug metabolism. Here, we investigated the influence of both furanochromones on AHR signaling in human HepG2 hepatocarcinoma cells and primary human hepatocytes. Both compounds transactivated xenobiotic response element (XRE)-driven reporter gene activity in a dose-dependent manner and induced CYP1A1 transcription in HepG2 cells and primary hepatocytes. The latter was abolished in presence of a specific AHR antagonist. CYP1A enzyme activity assays done in HepG2 cells and primary hepatocytes revealed an inhibition of enzyme activity by both furanochromones, which may become relevant regarding the metabolism of xenobiotics and co-administered therapeutic drugs. The observed induction of several other members of the AHR gene battery, whose gene products are involved in regulation of cell growth, differentiation and migration, indicates that a further toxicological characterization of visnagin and khelllin is urgently required in order to minimize potential drug-drug interactions and other toxic side-effects that may occur during therapeutic usage of these furanochromones.

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Anti-inflammatory effect of visnagin in lipopolysaccharide-stimulated BV-2 microglial cells

Cited by 47 publications

References 34 publications

Morphological Effects of Natural Products on Schizosaccharomyces pombe Measured by Imaging Flow Cytometry

Morphological Effects of Natural Products on Schizosaccharomyces pombe Measured by Imaging Flow Cytometry

Visnagin protects against doxorubicin-induced cardiomyopathy through modulation of mitochondrial malate dehydrogenase

Khellin and Visnagin Differentially Modulate AHR Signaling and Downstream CYP1A Activity in Human Liver Cells

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