Send to

Choose Destination
Sci Rep. 2018 Feb 14;8(1):3056. doi: 10.1038/s41598-018-21125-2.

Pharmacokinetic-pharmacodynamic correlations in the development of ginger extract as an anticancer agent.

Author information

Department of Biology, Georgia State University, Atlanta, GA-30303, USA.
ReaGene Biosciences Private Limited, Bengaluru, India.
Department of Biological Science and Technology, College of Biopharmaceutical and Food Sciences, China Medical University, Taichung, Taiwan, ROC.
Department of Biology, Georgia State University, Atlanta, GA-30303, USA.


Anticancer efficacy of ginger phenolics (GPs) has been demonstrated in various in vitro assays and xenograft mouse models. However, only sub-therapeutic plasma concentrations of GPs were detected in human and mouse pharmacokinetic (PK) studies. Intriguingly, a significant portion of GPs occurred as phase II metabolites (mainly glucuronide conjugates) in plasma. To evaluate the disposition of GPs and understand the real players responsible for efficacy, we performed a PK and tissue distribution study in mice. Plasma exposure of GPs was similar on day 1 and 7, suggesting no induction or inhibition of clearance pathways. Both free and conjugated GPs accumulated in all tissues including tumors. While non-cytotoxicity of 6-ginerol glucuronide precluded the role of conjugated GPs in cell death, the free forms were cytotoxic against prostate cancer cells. The efficacy of ginger was best explained by the reconversion of conjugated GPs to free forms by β-glucuronidase, which is over-expressed in the tumor tissue. This previously unrecognized two-step process suggests an instantaneous conversion of ingested free GPs into conjugated forms, followed by their subsequent absorption into systemic circulation and reconversion into free forms. This proposed model uncovers the mechanistic underpinnings of ginger's anticancer activity despite sub-therapeutic levels of free GPs in the plasma.

Supplemental Content

Full text links

Icon for Nature Publishing Group Icon for PubMed Central
Loading ...
Support Center