Dihydroperillic acid

Limonene was extensively metabolized by a variety of mammalian species [279, 290, 292, 301]. Its principal circulating metabolites identified in the rat were perillic acid and dihydroperillic acid. These components were effective inhibitors of isoprenylation and cellular proliferation in vitro [271]. 

Limonene inhibits the isoprenylation of a class of cellular proteins of 21-26 kDa, including p21ras and possibly other small GTP-binding proteins, in a dose-dependent manner in both cell lines (Crowell et al., 1991). Such inhibitors could alter signal transduction and result in altered gene expression (Gould, 1997). The two major rat serum metabolites of limonene, perillic acid and dihydroperillic acid, were more potent than limonene in the inhibition of isoprenylation (Crowell et al., 1991). These actions could explain the chemotherapeutic acitivity of limonene oils. 

Epidemiological studies demonstrate that dietary monoterpenes may be effective in the prevention and treatment of cancer [31]. Monocyclic monoterpenes D-limonene (Fig. 86.2) and perillyl alcohol (Fig. 86.4) are shown to inhibit the development of liver, skin, mammary, colon, lung, prostate, forestomach, and pancreatic carcinomas in a dose-dependent manner [29, 31-35]. Moreover, the metabolites of D-limonene such as perillic acid, dihydroperillic acid. 

When perillic acid is dissolved in five times its weight of amyl alcohol and is reduced by sodium at the boiling temperature, dihydro-perillic acid, CjoH Oj, is obtained. This acid melts at 107° to 109° C. By the reduction of its methyl ester by means of sodium, dihydroperillic alcohol is fornned, which is a liquid with a rose odour and having the following characters —... 

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