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Oregonin from Alnus incana bark affects DNA methyltransferases expression and mitochondrial DNA copies in mouse embryonic fibroblasts.

ABSTRACT: Oregonin is an open-chain diarylheptanoid isolated from Alnus incana bark that possesses remarkable antioxidant and anti-inflammatory properties, inhibits adipogenesis, and can be used in the prevention of obesity and related metabolic disorders. Here, we aimed to investigate the effects of oregonin on the epigenetic regulation in cells as well as its ability to modulate DNA methylating enzymes expression and mitochondrial DNA (mtDNA) copies. Our results show that oregonin altered the expression of DNA methyltransferases and mtDNA copy numbers in dependency on concentration and specificity of cells genotype. A close correlation between mtDNA copy numbers and mRNA expression of the mtDnmt1 and Dnmt3b was established. Moreover, molecular modeling suggested that oregonin fits the catalytic site of DNMT1 and partially overlaps with binding of the cofactor. These findings further extend the knowledge on oregonin, and elucidate for the first time its potential to affect the key players of the DNA methylation process, namely DNMTs transcripts and mtDNA.

SUBMITTER: Krasilnikova J

PROVIDER: S-EPMC6010114 | biostudies-literature | 2018 Dec

REPOSITORIES: biostudies-literature

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Oregonin from Alnus incana bark affects DNA methyltransferases expression and mitochondrial DNA copies in mouse embryonic fibroblasts.

Krasilnikova Jelena J Lauberte Liga L Stoyanova Elena E Abadjieva Desislava D Chervenkov Mihail M Mori Mattia M De Paolis Elisa E Mladenova Vanya V Telysheva Galina G Botta Bruno B Kistanova Elena E

Journal of enzyme inhibition and medicinal chemistry 20181201 1

Oregonin is an open-chain diarylheptanoid isolated from Alnus incana bark that possesses remarkable antioxidant and anti-inflammatory properties, inhibits adipogenesis, and can be used in the prevention of obesity and related metabolic disorders. Here, we aimed to investigate the effects of oregonin on the epigenetic regulation in cells as well as its ability to modulate DNA methylating enzymes expression and mitochondrial DNA (mtDNA) copies. Our results show that oregonin altered the expression ...[more]

PMID: 29877148

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Project description:Iron overload causes multiorgan dysfunction and serious damage. Alnus incana from the family Betulaceae, widely distributed in North America, is used for treating diseases. In this study, we investigated the iron chelating, antioxidant, anti-inflammatory, and antiapoptotic activities of the total and butanol extract from Alnus incana in iron-overloaded rats and identified the bioactive components in both extracts using liquid chromatography-mass spectrometry. We induced iron overload in the rats via six intramuscular injections of 12.5 mg iron dextran/100 g body weight for 30 days. The rats were then administered 60 mg ferrous sulfate /kg body weight once daily using a gastric tube. The total and butanol extracts were given orally, and the reference drug (deferoxamine) was administered subcutaneously for another month. After two months, we evaluated the biochemical, histopathological, histochemical, and immunohistochemical parameters. Iron overload significantly increased the serum iron level, liver biomarker activities, hepatic iron content, malondialdehyde, tumor necrosis factor-alpha, and caspase-3 levels. It also substantially (P < 0.05) reduced serum albumin, total protein, and total bilirubin content, and hepatic reduced glutathione levels. It caused severe histopathological alterations compared to the control rats, which were markedly (P < 0.05) ameliorated after treatment. The total extract exhibited significantly higher anti-inflammatory and antiapoptotic activities but lower antioxidant and iron-chelating activities than the butanol extract. Several polyphenolic compounds, including flavonoids and phenolic acids, were detected by ultraperformance liquid chromatography-electrospray ionization-quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) analysis. Our findings suggest that both extracts might alleviate iron overload-induced hepatoxicity and other pathological conditions characterized by hepatic iron overload, including thalassemia and sickle-cell anemia.

Dataset Information

Oregonin from Alnus incana bark affects DNA methyltransferases expression and mitochondrial DNA copies in mouse embryonic fibroblasts.

Publications

Oregonin from Alnus incana bark affects DNA methyltransferases expression and mitochondrial DNA copies in mouse embryonic fibroblasts.

Similar Datasets

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