Quercetin Enhances VDR Activity, Leading to Stimulation of Its Target Gene Expression in Caco-2 Cells

Abstract

Summary Vitamin D receptor (VDR) is a nuclear receptor that regulates the expression of genes involved in calcium homeostasis. Activation of VDR is thought to be a promising drug target for osteoporosis. Using a VDR-driven luciferase expression assay for screening a naturally occurring food component, we identified quercetin as a VDR activator. Quercetin also activated the GAL4 DNA-binding domain fused to the VDR ligand-binding domain. Moreover, it was confirmed that quercetin increases the mRNA level of TRPV6, which is a VDR target gene, in Caco-2 cells. These results indicate that quercetin enhances VDR activity through the alteration of cofactor recruitment, thereby stimulating its target genes while providing a new function for quercetin as the VDR activator.

Potential Antiosteoporotic Agents from Plants: A Comprehensive Review

“…These compounds can be divided into 6 categories, including flavonoids: icariin (Figure 1) [23–26], genistein (Figure 2) [29], daidzein (Figure 2) [31, 32], kaempferol (Figure 11) [72], quercetin (Figure 11) [73, 74], naringin (Figure 8) [75–77], hesperidin (Figure 11) [78], linarin (Figure 11) [79], bavachalcone (Figure 3) [36], rutin (Figure 11) [80], (+)-catechin (Figure 11) [81], nobiletin (Figure 11) [82], luteolin (Figure 11) [83], baicalein (Figure 11) [84], baicalin (Figure 1) [85], xanthohumol (Figure 11) [86]; coumarins: psoralen (Figure 3) [35], osthole (Figure 11) [87]; lignans: honokiol (Figure 11) [88, 89], isotaxiresinol (Figure 11) [90], magnolol (Figure 11) [91]; polyphenol: resveratrol (Figure 11) [92–95], curcumin (Figure 11) [96–98], tea polyphenols (including epigallocatechin-3-gallate, epigallocatechin, epi-catechin, epicatechin-3-gallate, Figure 11) [99, 100]; anthraquinones: rubiadin (Figure 10), 2-hydroxy-1-methoxy-anthraquinone (Figure 10), 1,3,8-trihydroxy-2-methoxy-anthraquinone (Figure 10) [71]; alkaloids: harmine (Figure 11) [101], coptisine (Figure 11) [102], palmatine (Figure 11) [103], berberine (Figure 11) [104, 105]; and other compounds: curculigoside (Figure 11) [106, 107], asperosaponin VI (Figure 11) [108], limonoid 7-oxo-deacetoxygeduni...…”

Inhibition of Vitamin D Receptor Translocation by Cigarette Smoking Extracts

“…Also, the action is known due to strong antioxidant. The reason of using quercetin in the study is that quercetin increases the target genome of the VDR, TRPV6 mRNA and it is because quercetin increases the VDR activation22. Unlike quercetin, n-acetylcysteine used in the study may not inhibit the VDR translocation from the CSE.…”

Effect of Quercetin Supplement on Some Bone Mineralization Biomarkers in Diabetic Type 2 Patients

“…& et al in 2012, where treatment of rats with quercetin resulted in elevation of serum calcium as compared with group with gentamicin nephrotoxicity [36]. The mechanism behind elevation of serum calcium in our study is not well understood, but may be related to potent antioxidant effect of quercetin that may correct redox status in small intestine at cellular level [37]; activation of TRPV6 gene expression and activation of vitamin D receptor in intestine [38] leading to improvement of calcium absorption [39].…”

“…Quercetin induces activation of TRPV6 gene expression, that in turn, lead to the elevate expression level of CYP27B1 and then production of 25(OH) vitamin D alpha hydroxylase; the enzyme required to conversion of 25(OH) vitamin D to more potent Vitamin D metabolite called 1,25di(OH) vitamin D [41]. Both Increment in level of 1,25di(OH) vitamin D and Quercetin mimic effect of 1,25di(OH) vitamin D on its receptor (VDR) [39], both actions lead to elevation in serum calcium, [42] and hence may reduce parathyroid hormone [42], these possible two last changes may reduce conversion of 25(OH) vitamin D to 1,25di(OH) vitamin D and then increase serum level of 25(OH) vitamin D.…”