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  5. Modulation of PXR Activity by Ginger and its Constituents
  1. The FDA Science Forum

2021 FDA Science Forum

Modulation of PXR Activity by Ginger and its Constituents

Download the Poster (PDF; 0.52 MB)
Authors:
Poster Author(s)
Husain, Islam, National Center for Natural Products Research, School of Pharmacy, The University of Mississippi; Ali, Zulfiqar, National Center for Natural Products Research, School of Pharmacy, The University of Mississippi; Chittiboyina, Amar G, National Center for Natural Products Research, School of Pharmacy, The University of Mississippi ; Khan, Ikhlas A, National Center for Natural Products Research and Department of Bio-Molecular Sciences, School of Pharmacy, The University of Mississippi; Noonan, Gregory O, FDA/CFSAN; Khan, Shabana I, National Center for Natural Products Research and Department of Bio-Molecular Sciences, School of Pharmacy, The University of Mississippi
Center:
Contributing Office
Center for Food Safety and Applied Nutrition

Abstract

Poster Abstract

Ginger root (Zingiber officinale) is widely used in food as a spice and flavoring agent, and it is an integral part of Southeast Asia’s traditional medicine to treat various human ailments such as the common cold, inflammation, rheumatic disorder, and gastrointestinal discomforts. A quick search in NIH’s Dietary Supplement Label Database resulted in more than 3,500 ginger-based products sold via major retailers in the US. In our pursuit to assure the quality and safety of botanical ingredients in various matrices and due to a lack of scientific data on these ingredients’ potential adverse effects, root extract of ginger and its principal components were investigated for possibility of herb-drug interactions through activating pregnane-X-receptor (PXR), which regulates the expression of drug-metabolizing enzymes and transporters (DMET). Our preliminary findings suggested that ethanolic extract of ginger at a 20 µg/mL concentration activated PXR up to 2.31 fold in LS-174T cells. Among the constituents, 6-paradoal, 6-shagoal, and dihydro-6-6-gingerdione at 30 µM activated the PXR up to 2.1, 3.4, and 2.9 fold, respectively. However, 6-gingerol and 6-gingerdiol were less potent, and fold activation was below two-fold. Gene expression analysis by RT-PCR showed increased expression of CYP3A4, CYP2C9, CYP1A2, CYP2B6, and P-gP mRNA by the extract, 6-paradoal, 6-shagoal, and dihydro-6-6-gingerdione to variable extents. These results suggest that ginger and some of its constituents may enhance DMET activity by directly increasing the transcriptional activity of PXR. Further studies are in progress to determine the effect of ginger on the activity of the functional proteins and their impact on the pharmacokinetics of concomitantly consumed drugs.

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Download the Poster (PDF; 0.52 MB)

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