Fruit Extract, Rich in Polyphenols and Flavonoids, Modifies the Expression of DNMT and HDAC Genes Involved in Epigenetic Processes

Abstract

Recently, the field of epigenetics has been intensively studied in relation to nutrition. In our study, the gene expression patterns of histone deacetylases (HDACs), which regulate the stability of histone proteins, and DNA methyltransferases (DNMTs), which regulate DNA methylation, were determined in mice. The animals were fed a human-equivalent dose of the aqueous extract of fruit seeds and peels, which is rich in flavonoids and polyphenols, for 28 days and then exposed to the carcinogen 7,12-dimethylbenz(a)anthracene (DMBA). The concentrations of trans-resveratrol and trans-piceid were determined in the consumed extract by HPLC and were 1.74 mg/L (SD 0.13 mg/L) and 2.37 mg/L (SD 0.32 mg/L), respectively, which corresponds to the consumption of 0.2–1 L of red wine, the main dietary source of resveratrol, in humans daily. Subsequently, 24 h after DMBA exposure, the expression patterns of the HDAC and DNMT genes in the liver and kidneys were determined by qRT-PCR. The DMBA-induced expression of the tested genes HDAC1, HDAC2, DNMT1, DNMT3A and DNMT3B was reduced in most cases by the extract. It has already been shown that inhibition of the DNMT and HDAC genes may delay cancer development and tumour progression. We hypothesise that the extract studied may exert chemopreventive effects.

Efficacy and safety of Abelmoschus manihot capsule combined with ACEI/ARB on diabetic kidney disease: a systematic review and meta analysis

“…Additionally, TFA can also inhibit histone acetyltransferase p300 (HAT p300), reducing the degree of acetylation of histone H3, thereby alleviating the undesirable "metabolic memory" effect. Subsequently, this mechanism can inhibit the transcriptional activity of the components of the extracellular matrix and downregulate the expression of the linker proteins fibronectin, laminin, and collagen, thereby reducing renal inflammation and fibrosis (Ramaiah et al, 2021;Nowrasteh et al, 2023). At the translational level, TFA can directly inhibit the activity of the renal fibrosis-promoting histone deacetylase 3 (HDAC3) and activate the action of the renal fibrosis-inhibiting SIRT1, thereby negatively regulating the process of renal fibrosis, slowing down the onset and development of DKD (Huang et al, 2016;Liu et al, 2020).…”

Garlic‐derived compounds: Epigenetic modulators and their antitumor effects

“…Recent studies have demonstrated that plant‐derived natural products have great potential in the treatment of epigenetic characteristics of cancer (Fang et al, 2020; D. Huang et al, 2019). Plant‐derived natural products are considered to promise epigenetic drugs for tumor prevention and treatment in the future, such as protoberberine alkaloids, flavones, polyphenols, and cyclic peptides, which have been evaluated in clinical trials (Fang et al, 2020; Karaman Mayack et al, 2020; Ming et al, 2022; Nowrasteh et al, 2023; Pontes et al, 2023). Up to now, natural products are increasingly becoming the focus of research in the field of tumor therapy and new drug discovery.…”

Phytochemicals in Chronic Disease Prevention

“…A mixture of aqueous extracts derived from red grape, blackcurrant, redcurrant, rosehip, and black cherry was characterized by the presence of 1.74 mg/L trans-resveratrol and 2.37 mg/L trans-piceid. This mixture exhibited anticancer effects by inhibiting the expression levels of DNA methyltransferases (DNMT1, DNMT3A, and DNMT3B) and histone deacetylases (HDAC2 and HDAC3) in a mouse model exposed to the carcinogen 7,12dimethylbenz(a)anthracene [19]. Recently, fruit juice consumption has become more popular than the consumption of fresh fruits.…”