Another literature has shown an increased biosynthesis of carvacrol in shoot
cultures of the Iranian plant Satureja khuzistanica by inhibiting the mevalonate
pathway (Ramak et al. 2013). The methylerythritol-4-phosphate (MEP) pathway
provides isopentenyl diphosphate (IPP) which was the precursor for the biosynthesis of 90% carvacrol. Figure 13.2 showed that carvacrol was biosynthesized
from isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMADP)
which were derived via the MEP pathway located in plastids (Rohmer et al. 1993;
Dudareva et al. 2005) of oregano and thyme. IPP is reversibly converted to
DMADP by isopentenyl diphosphate isomerase (IDI). The irreversible conversion
of 1-deoxy-D-xylulose-5-phosphate (DXP) into 2-C-methyl-D-erythritol-4- phosphate (MEP) was catalyzed by 1-deoxy-D-xylulose-5-phosphate reductoisomerase
enzyme (DXR) (Takahashi et al. 1998). The condensation of IPP and DMADP
produced geranyl diphosphate (GDP) and that was catalyzed by the geranyl
diphosphate synthase (GDS) enzyme (Lichtenthaler 1999; Burke et al. 1999; Majdi
et al. 2017). The cyclization of GDP by gamma-terpinene synthase produced
gamma-terpinene. The enzymes such as CYP71D178, CYP71D180, and
CYP71D181 of cytochrome P450 (CYP) monooxygenases converted c-terpinene to
yield carvacrol (Crocoll et al. 2010; Crocoll 2011).
13.5 Physical Properties
It is found in liquid form having molecular weight 150.22. Its boiling point is about
237− 238 °C; density is 0.967 and melting point 0 °C. Its k max value showed
277.5 nm in 95% ethanol in the UV spectrophotometer. Its pKa value is 10.9. It is
insoluble in water, soluble in 95% ethanol. Carvacrol has a pleasant pungent taste
and odor, sweet and spicy like marjoram (Ramak et al. 2013; Friedman 2014).
13.6 Metabolism and Excretion of Carvacrol
Carvacrol’s ADME process in the human body system is very rapid and it follows
two types of pathways. The major metabolic pathway of carvacrol depends on the
phase II metabolism related to the esterification of phenolic group of carvacrol by
glucuronidation and sulfation, but when used in low dose, another minor route of
carvacrol metabolism was also observed. In the minor pathway transformation of
the terminal methyl groups to primary alcohols took place (Alagawany 2015; Dong
et al. 2012).
Austgulen et al. 1987 also showed the pattern of metabolism of carvacrol
(Fig. 13.3) in male albino rats. After administration by oral route at a dose of
1 mM/kg, the major portion of metabolites was excreted through urine where seven
metabolites of carvacrol were identified, such as 2,3-dihydroxy-p-cymene, 2(3-hydroxy-4-methyl phenyl) propan-2-ol, 2-(3-hydroxy-4-methyl phenyl)
13 Carvacrol (Origanum vulgare): Therapeutic Properties …
441
cultures of the Iranian plant Satureja khuzistanica by inhibiting the mevalonate
pathway (Ramak et al. 2013). The methylerythritol-4-phosphate (MEP) pathway
provides isopentenyl diphosphate (IPP) which was the precursor for the biosynthesis of 90% carvacrol. Figure 13.2 showed that carvacrol was biosynthesized
from isopentenyl diphosphate (IPP) and dimethylallyl diphosphate (DMADP)
which were derived via the MEP pathway located in plastids (Rohmer et al. 1993;
Dudareva et al. 2005) of oregano and thyme. IPP is reversibly converted to
DMADP by isopentenyl diphosphate isomerase (IDI). The irreversible conversion
of 1-deoxy-D-xylulose-5-phosphate (DXP) into 2-C-methyl-D-erythritol-4- phosphate (MEP) was catalyzed by 1-deoxy-D-xylulose-5-phosphate reductoisomerase
enzyme (DXR) (Takahashi et al. 1998). The condensation of IPP and DMADP
produced geranyl diphosphate (GDP) and that was catalyzed by the geranyl
diphosphate synthase (GDS) enzyme (Lichtenthaler 1999; Burke et al. 1999; Majdi
et al. 2017). The cyclization of GDP by gamma-terpinene synthase produced
gamma-terpinene. The enzymes such as CYP71D178, CYP71D180, and
CYP71D181 of cytochrome P450 (CYP) monooxygenases converted c-terpinene to
yield carvacrol (Crocoll et al. 2010; Crocoll 2011).
13.5 Physical Properties
It is found in liquid form having molecular weight 150.22. Its boiling point is about
237− 238 °C; density is 0.967 and melting point 0 °C. Its k max value showed
277.5 nm in 95% ethanol in the UV spectrophotometer. Its pKa value is 10.9. It is
insoluble in water, soluble in 95% ethanol. Carvacrol has a pleasant pungent taste
and odor, sweet and spicy like marjoram (Ramak et al. 2013; Friedman 2014).
13.6 Metabolism and Excretion of Carvacrol
Carvacrol’s ADME process in the human body system is very rapid and it follows
two types of pathways. The major metabolic pathway of carvacrol depends on the
phase II metabolism related to the esterification of phenolic group of carvacrol by
glucuronidation and sulfation, but when used in low dose, another minor route of
carvacrol metabolism was also observed. In the minor pathway transformation of
the terminal methyl groups to primary alcohols took place (Alagawany 2015; Dong
et al. 2012).
Austgulen et al. 1987 also showed the pattern of metabolism of carvacrol
(Fig. 13.3) in male albino rats. After administration by oral route at a dose of
1 mM/kg, the major portion of metabolites was excreted through urine where seven
metabolites of carvacrol were identified, such as 2,3-dihydroxy-p-cymene, 2(3-hydroxy-4-methyl phenyl) propan-2-ol, 2-(3-hydroxy-4-methyl phenyl)
13 Carvacrol (Origanum vulgare): Therapeutic Properties …
441