The Roles of Natural Compounds in Epigenetics

Yang, Yanhong; Chi, Zuo-Hua; Gao, Rui; Lei, Zili

doi:10.1177/1934578x1801300835

Cited by 2 publications

(2 citation statements)

References 75 publications

(83 reference statements)

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“…DADS decreased the proliferation and invasion of osteosarcoma cells by upregulating miR-134 expression (7) and prevented cigarette smoke-induced airway inflammation by inhibiting the phosphorylation of extracellular signal-regulated kinase and the expression of matrix metalloproteinase-9 in lung tissues (8). DADS may also exhibit epigenetic regulation by exerting histone deacetylase-inhibitory activity (9,10).…”

Section: Introductionmentioning

confidence: 99%

Fatty liver and alteration of the gut microbiome induced by diallyl disulfide

Yang

Huang

et al. 2019

Int J Mol Med

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Diallyl disulfide (DADS) is one of the primary components of garlic and it exhibits a broad range of biological activities. In the present study, the effects of DADS on lipid metabolism and its potential role in the modulation of the gut microbiome were determined. Hematoxylin and eosin and oil-red O staining were used to assess the liver and intestinal tissues of mice treated with DADS. The expression of lipid metabolism-associated genes was measured using reverse transcription-quantitative PCR (RT-qPCR). The effects of DADS on the gut microbiome were measured using 16S recombinant (r)DNA gene analysis. The results revealed that the serum non-esterified free fatty acids, high density lipopro-tein-cholesterol, low density lipoprotein-cholesterol, serum total cholesterol, liver triglyceride and total cholesterol levels of the mice fed with a low-dose of DADS was significantly higher when compared with the control. Hematoxylin and eosin and oil-red O staining demonstrated that DADS induced fatty liver in mice. The results of the RT-qPCR revealed that the expression levels of a number of lipid metabolism-associated genes were altered in the livers of mice treated with DADS.The 16S rDNA gene analysis demonstrated that the mice fed on a normal diet treated with a low-dose of DADS had decreased levels of bacteria from the Bacteroidetes phyla and increased levels of bacteria from the Firmicutes phyla. The Kyoto Encyclopedia of Genes and Genomes pathway analysis revealed the top 20 pathways enriched in the low-dose DADS group of mice fed with a normal diet. In the present study, low-dose DADS induced fatty liver and altered the gut micro-biota, similar to the phenotype induced by a high fat diet, by regulating the expression of lipid metabolism associated genes.

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Section: Introductionmentioning

confidence: 99%

Fatty liver and alteration of the gut microbiome induced by diallyl disulfide

Yang

Huang

et al. 2019

Int J Mol Med

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“…Natural compounds have always been a major source of biologically active substances, and many are known for their effect on epigenetic processes such as DNA methylation, histone marks and lncRNAs ( Yang et al, 2018 ). The KDM enzymes are no exception; for example, several natural products like resveratrol, curcumin and melatonin have been reported as inhibitors of the LSD1 enzymes ( Fang et al, 2020 ).…”

Section: Introductionmentioning

confidence: 99%

Transcriptomic and Drug Discovery Analyses Reveal Natural Compounds Targeting the KDM4 Subfamily as Promising Adjuvant Treatments in Cancer

et al. 2022

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KDM4 proteins are a subfamily of histone demethylases that target the trimethylation of lysines 9 and 36 of histone H3, which are associated with transcriptional repression and elongation respectively. Their deregulation in cancer may lead to chromatin structure alteration and transcriptional defects that could promote malignancy. Despite that KDM4 proteins are promising drug targets in cancer therapy, only a few drugs have been described as inhibitors of these enzymes, while studies on natural compounds as possible inhibitors are still needed. Natural compounds are a major source of biologically active substances and many are known to target epigenetic processes such as DNA methylation and histone deacetylation, making them a rich source for the discovery of new histone demethylase inhibitors. Here, using transcriptomic analyses we determined that the KDM4 family is deregulated and associated with a poor prognosis in multiple neoplastic tissues. Also, by molecular docking and molecular dynamics approaches, we screened the COCONUT database to search for inhibitors of natural origin compared to FDA-approved drugs and DrugBank databases. We found that molecules from natural products presented the best scores in the FRED docking analysis. Molecules with sugars, aromatic rings, and the presence of OH or O- groups favor the interaction with the active site of KDM4 subfamily proteins. Finally, we integrated a protein-protein interaction network to correlate data from transcriptomic analysis and docking screenings to propose FDA-approved drugs that could be used as multitarget therapies or in combination with the potential natural inhibitors of KDM4 enzymes. This study highlights the relevance of the KDM4 family in cancer and proposes natural compounds that could be used as potential therapies.

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The Roles of Natural Compounds in Epigenetics

Cited by 2 publications

References 75 publications

Fatty liver and alteration of the gut microbiome induced by diallyl disulfide

Fatty liver and alteration of the gut microbiome induced by diallyl disulfide

Transcriptomic and Drug Discovery Analyses Reveal Natural Compounds Targeting the KDM4 Subfamily as Promising Adjuvant Treatments in Cancer

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