Planta Med 2016; 82(01/02): 121-130
DOI: 10.1055/s-0035-1557898
Pharmacokinetic Investigations
Original Papers
Georg Thieme Verlag KG Stuttgart · New York

Vitamin D Receptor-Mediated Upregulation of CYP3A4 and MDR1 by Quercetin in Caco-2 cells

Yoon-Jee Chae*
1   Chong Kun Dang Research Institute, CKD Pharmaceuticals Inc., Jung-dong, Giheung, Yongin, Gyeonggi, Republic of Korea
Kwan Hyung Cho*
2   College of Pharmacy, Inje University, Obang-dong, Gimhae, Gyeongnam, Republic of Korea
In-Soo Yoon
3   College of Pharmacy and Natural Medicine Research Institute, Mokpo National University, Muan-gun, Jeonnam, Republic of Korea
Chi-Kyoung Noh
4   College of Pharmacy, Seoul National University, Seoul, Republic of Korea
Hyo-Jong Lee
2   College of Pharmacy, Inje University, Obang-dong, Gimhae, Gyeongnam, Republic of Korea
Yohan Park
2   College of Pharmacy, Inje University, Obang-dong, Gimhae, Gyeongnam, Republic of Korea
Eunhee Ji
5   College of Pharmacy, Gachon University, Yeonsu-gu, Incheon, Republic of Korea
Min-Duk Seo
6   College of Pharmacy, Ajou University, Suwon, Kyeonggi, Republic of Korea
7   Department of Molecular Science and Technology, Ajou University, Suwon, Kyeonggi, Republic of Korea
Han-Joo Maeng
5   College of Pharmacy, Gachon University, Yeonsu-gu, Incheon, Republic of Korea
› Author Affiliations
Further Information

Publication History

received 12 May 2015
revised 22 July 2015

accepted 27 July 2015

Publication Date:
14 September 2015 (online)


To examine whether quercetin interacts with vitamin D receptor, we investigated the effects of quercetin on vitamin D receptor activity in human intestinal Caco-2 cells. The effects of quercetin on the expression of the vitamin D receptor target genes, vitamin D3 24-hydroxylase, cytochrome P450 3A4, multidrug resistance protein 1, and transient receptor potential vanilloid type 6 were measured using quantitative polymerase chain reaction. The vitamin D receptor siRNA was used to assess the involvement of the vitamin D receptor. Vitamin D receptor activation using a vitamin D responsive element-mediated cytochrome P450 3A4 reporter gene assay was investigated in Caco-2 cells transfected with human vitamin D receptor. We also studied the magnitude of the vitamin D receptor activation and/or synergism between 1α,25-dihydroxyvitamin D3 [1,25(OH)2D3] and quercetin-like flavonoids. Slight but significant increases in the mRNA expression of cytochrome P450 3A4, vitamin D3 24-hydroxylase, multidrug resistance protein 1, and transient receptor potential vanilloid type 6 were observed after 3 days of continual quercetin treatment. The silencing effect of vitamin D receptor by vitamin D receptor siRNA in Caco-2 cells significantly attenuated the induction of the vitamin D receptor target genes. Moreover, quercetin significantly enhanced cytochrome P450 3A4 reporter activity in Caco-2 cells in a dose-dependent manner, and the expression of exogenous vitamin D receptor further stimulated the vitamin D receptor activity. Quercetin-like flavonoids such as kaempferol stimulated the vitamin D receptor activity in a manner similar to that seen with quercetin. Taken together, the data indicates that quercetin upregulates cytochrome P450 3A4 and multidrug resistance protein 1 expression in Caco-2 cells likely via a vitamin D receptor-dependent pathway.

* These authors contributed equally to this work.

Supporting Information

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