Even though ginger has been utilized in various studies in man and animals, there is a relative dearth of information on the pharmacological properties of ginger disposition in treated subjects. At the end of bolus intravenous administration at a dose of 3 mg/kg of [6]-gingerol (1), the plasma rate of concentration–time curve was drawn by a two-compartment open model.[6]-Gingerol was quickly cleared from plasma with a terminal half-life of 7.23 min and an overall body clearance of 16.8 ml/min/kg. Serum protein binding of [6]-gingerol was 92.4% ( according to Ding et al., 1991). Identical group studied the kinetics in mice with either experimental acute hepatic or renal failure ( according to Naora et al., 1992) and  result that there was difference in either the plasma concentration–time curve or any pharmacokinetic parameters between the control and nephrectomized mice. It is described, therefore, that  the renal excretion does not contribute totally to the disappearance of [6]-gingerol from plasma in mice. On the other hand, hepatic toxicity raised the plasma concentration of [6]-gingerol at the terminal phase. Its elimination half-life increased, significantly, from 8.5 to 11.0 min, in mice with hepatic damage. The extent of [6]-gingerol bound to serum protein was  90% and more which  was affected very slightly by the toxicity. These aspects indicate that [6]-the properties of ginger is  partly eliminated by the liver.

Gingerol activity in the overall  properties of ginger

A reduction for the metabolism of S-(+)-[6]-gingerol (1) in the major pungent property of ginger, was studied in vitro with phenobarbital-induced rat liver 10,000gm supernatant having the NADPH-generating system (Surh and Lee, 1994). The reduction resulted stereo-specific power and the ethyl acetate-extractable products were separated  and two metabolites were identified as diastereomers of [6]-gingerdiol by gas chromatography/mass spectrometry. Similar authors have recently  shown that [6]-shogaol (2), a pungent principle of ginger, was minimized in rat liver in vitro. Ethyl acetate-extractable metabolites of shogaol were isolated, made  by incubation of this alpha, beta-unsaturated ketone with a rat liver cytosolic fraction fortified with either NADPH- or NADPH-generating system;  two main metabolites were identified as 1-(4- hydroxy-3-methoxyphenyl)-decan-3-one {[6]-paradol (11)} and 1-(4-hydroxy-3-methoxy)-decan-3-ol (reduced [6]-paradol). 1-(4-Hydroxy-3-methoxyphenyl)-deca-1-ene-3-one (dehydroparadol), a non-pungent analog of shogaol, formed the same metabolites, as did [6]-shogaol under the same incubation conditions. [6]-Paradol is shown to be a middle bridge in the reductive metabolism of the alpha, beta-unsaturated ketone moiety of shogaol to the corresponding saturated alcohol (Surh and Lee, 1994). The pharmacological works of these isolated metabolites have not been characterized. Recently, it has been reported that [6]-gingerol, when incubated with NADPH-fortified rat hepatic microsomes, outputs up to eight metabolites, which were tentatively known by gas chromatographic–mass spectrometric (GC–MS) analysis as two products of aromatic hydroxylation,as well as the diastereomers of two aliphatic hydroxylation products and the diastereomers of [6]-gingerdiol.

gingerol structure in the properties of ginger

Hepatic microsomes from mice and humans, fortified with  glucuronidated [6]-gingerol and UDPGA mainly at the phenolic hydroxyl group, but less amounts of a second monoglucuronide activating  the aliphatic hydroxyl group were also identified by fluid chromatography-mass spectrometry/

mass spectrometry (LC-MS/MS) analysis. Human intestinal microsomes  formed only as a phenolic glucuronide.Supersomes storing  human UGT1A1 and 1A3 uniquely  generated the phenolic glucuronide, albeit with too low activities, whereas UGT1A9 catalyzed the specific formation of the alcoholic glucuronide, and UGT2B7 the predominant generation of the phenolic glucuronide, with high activities. This research indicates a rather complex metabolism of [6]-gingerol, which, according to the authors, should be taken into consideration for the multi- biological activities of this compound (Pfeiffer et al., 2006).

The metabolic fate of [6]-gingerol was investigated in mice by Nakazawa and Ohsawa (2002). The bile of mice that had been orally administered [6]-gingerol was shown by high-power liquid chromatographic (HPLC) analysis containing a major metabolite (S)-[6]-gingerol-40 O-b-glucuronide. Although proprties of ginger from the metabolites derived from [6]-gingerol were not seen in the urine, the ethyl acetate extract of the urine, after enzymatic hydrolysis, was shown to contain six  metabolites mith minor metabolic activities  {vanillic acid, ferulic acid (S)-(+)-4-hydroxy-6-oxo-8-(4-hydroxy-3-methoxyphenyl)- 4-(4-hydroxy-3-methoxyphenyl)butanoic, octanoic acid, 9-hydroxy[6]-gingerol and (S)-(+)-[6]-gingerol}. The overall  amount of the major metabolite excreted in the bile and of the six metabolites in the urine during 60 h after the oral administration of [6]-gingerol were almost 48% and 16% of the dose, respectively. The excretion of the six minor metabolites in the urine Lowered after gut sterilization, possibly suggesting the member of gut flora in the metabolism.When we come to hydroxyl pesence, the incubation of [6]-gingerol with rat liver showed the existence  of 9-hydroxy-[6]-gingerol, gingerdiol, and (S)-[6]- gingerol-40-O-b-glucuronide. These findings suggest that the pharmacological properties of ginger both the gut flora, as well as enzymes in the liver, play y an essential  part in the metabolism of [6]-gingerol.

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