Abstract
Vitamin D plays an important role in every tissue due to its differentiating properties and the control of calcium homeostasis. The reversion of the epigenetic repression of the vitamin D receptor (VDR) could lead to an increased sensitivity of the cells to the beneficial activity of the hormone and could be exploited in many vitamin D-resistant diseases. In this study we analyzed the effects of three natural epigenetic modulators: sulforaphane, curcumin, and the products of the fermentative activity of probiotics. Sulforaphane and curcumin are inhibitors of the DNA methyltransferases (DNMT) and of the histone deacetylases (HDAC); it has been demonstrated that sulforaphane and curcumin increase VDR expression in intestinal epithelial cells and in a human liver cancer cell line, respectively. The anti-inflammatory properties associated with the probiotic administration in vivo can be linked to the increased activity of intestinal VDR. Butyrate, an inhibitor of HDAC and a known modulator of VDR expression, is the candidate byproduct of fermentation by gut microbiome that could mediate the enhanced expression of VDR triggered by probiotics in vivo. Many other natural compounds wait to be investigated and recognized as epigenetic modulators of VDR, thus opening promising therapeutic avenues for many diseases by natural means.
Highlights
The scientific community has shown an ever growing interest towards natural epigenetic modulators; among them, natural molecules as curcumin, sulforaphane, resveratrol, genistein, and polyphenols have proved to be able to act as epigenetic modulators, influencing the activity of chromatin modifiers and transcriptional factors [1]
Given the central role of vitamin D receptor (VDR) in healthy tissues and considering its frequent silencing, due to a faulty epigenetic remodeling occurring during differentiation, or to the epigenetic defects accumulated during neoplastic transformation, the ability to restore VDR expression and activity could be crucial in many conditions
The resistance to vitamin D could be overcome by altering the epigenetic control of VDR
Summary
The scientific community has shown an ever growing interest towards natural epigenetic modulators; among them, natural molecules as curcumin, sulforaphane, resveratrol, genistein, and polyphenols have proved to be able to act as epigenetic modulators, influencing the activity of chromatin modifiers and transcriptional factors [1] The effects of these molecules have been exploited for therapeutic purposes and these compounds have been employed to increase the sensitivity of cancer cells to conventional chemotherapeutic agents [2]. Dietary supplementation of sulforaphane ameliorates liver function and insulin resistance in diabetes II patients [18,19] Because of their high efficacy and safety, at the moment there are 64 ongoing clinical trials on curcumin and 19 on sulforaphane (https://clinicaltrials.gov/). This review is aimed at illustrating the ability of three nutraceuticals to modulate the expression of vitamin D receptor and their beneficial effects on health due to the enhanced ubiquitous actions exerted by vitamin D; this collection of initial observations is meant to stimulate the search for other natural compounds with similar activity
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