Pharmacokinetics of 10-gingerol and 6-shogaol in the plasma of healthy subjects treated with red ginger (Zingiber officinale var. Rubrum) suspension

Abstract

Red ginger (Zingiber officinale var. Rubrum) is among the most widely consumed medicinal herbs in Indonesia. Ginger rhizome contains phenol compounds including gingerol and shogaol. 10-gingerol has been reported to exhibit the greatest anti-inflammatory and anti-oxidant activities compared with those of other gingerols. Pharmacokinetic studies on ginger have been reported, but there is a lack of such study on red ginger. The present work studied the pharmacokinetics of 10-gingerol and 6-shogaol in the plasma of healthy subjects treated with a single dose of red ginger suspension. Healthy subjects (n=19) were given a single dose of red ginger suspension (2 g/15 ml), and blood samples were taken at baseline (0 min), 30, 60, 90, 120, and 180 min. Analysis of 10-gingerol and 6-shogaol was performed by dissolving 200 µl of the subjects' plasma in 800 µl acetonitrile. The mixture was vortexed and centrifuged at 20,440 × g for 15 min at room temperature. The supernatant was filtered using Millipore membrane (pore size 0.2 µm) and injected into an RP-C18 column for liquid chromatography-mass spectrometry. A mixture of 0.1% (v/v) formic acid in water and acetonitrile (38:62) was used as the mobile phase. The maximum plasma concentration (Cmax) and time to reach Cmax of 10-gingerol and 6-shogaol were 160.49 ng/ml (38 min) and 453.40 ng/ml (30 min), respectively. The elimination half-lives were 336 and 149 min for 10-gingerol and 6-shogaol, respectively. Thus, 10-gingerol and 6-shogaol were absorbed after per oral single dose of red ginger suspension and could be quantified in the plasma of the healthy subjects. Additionally, the red ginger analytes exhibited relatively slow elimination half-lives.

Keywords: Zingiber officinale var. Rubrum; Zingiberaceae; antiinflammation; gingerol; oleoresins; phenols; shogaol.

Figure 1.

Chemical structure of (A) 10-gingerol and (B) 6-shogaol, downloaded from http://www.chemspider.com/Chemical-Structure.147055.html?rid=a2e8c30f-67ff-43bb-9b9d-b526a54aae92&page_num=0 for 10-gingerol and http://www.chemspider.com/Chemical-Structure.4445106.html?rid=aff2295b-35aa-43d5-807a-8b26311f4469 for 6-shogaol and redrawn using ChemDraw Professional 15.0.0.106 (PerkenElmer, Waltham, MA, USA; licensed to Padjadjaran University, West Java, Indonesia, no. 623018920).

Figure 2.

Ultraviolet spectra of 10-gingerol standard (λmax=284 nm; A=0.0315); 6-shogaol standard (λmax=282 nm; A=0.1834); red ginger suspension (λmax=286 nm; A=0.4203). λmax, maximum wavelength; A, absorbance.

Figure 3.

Representative chromatogram of human plasma spiked with 6-shogaol standard (retention time=6.70 min) (upper panel); and the mass spectrum of 6-shogaol [M+1] (m/z=277.3869; MW 6-shogaol=276.376) (lower panel).

Figure 4.

Representative chromatogram of human plasma spiked with 10-gingerol standard (retention time=8.26 min) (upper panel); and the mass spectrum of 10-gingerol [M+1] (m/z=351.2959; MW 10-gingerol=350.4923) (lower panel).

Figure 5.

Chromatograms of human plasma spiked with various concentrations of 6-shogaol standard (retention time=6.70 min).

Figure 6.

Chromatograms of 10-gingerol (blue rectangle; t_R=8.0 min) and 6-shogaol (red rectangle; t_R=6.80 min) in the plasma of 19 subjects after 30 min treatment with red ginger suspension. A mixture of 0.1% (v/v) formic acid in water and acetonitrile (38:62) was used asthe mobile phase. t_R, retention time.