d-Limonene, a cyclic terpene that is a major component of several plant essential oils, is used widely as an additive in perfumes, soaps, foods and beverages, and has also been shown to possess chemopreventative and chemotherapeutic activity. A limited number of studies have been conducted investigating the effect of d-limonene on immune system function. We show that d-limonene and its metabolites limonene-1-2-diol and perillic acid inhibit the production by CD3(+)CD4(+) T cells of IFN-γ, IL-2, TNF-α, IL-4 and IL-13, and the production by CD3(+)CD8(+) T cells of IFN-γ, IL-2, and TNF-α. Additionally, the upregulation of CD25, CD69 and CD40L by activated T lymphocytes is modulated by d-limonene, limonene-1-2-diol and perillic acid treatment. Furthermore, high concentrations of d-limonene, limonene-1-2-diol and perillic acid induce T lymphocyte cell death. These data suggest that d-limonene possesses immunomodulatory activity that must be considered when utilizing the compound for therapeutic or commercial purposes.
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Review of toxicological assessment of d-limonene, a food and cosmetics additive.
Food Chem Toxicol
October 2018
Department of Food Science and Technology, National Institute of Food Technology Entrepreneurship and Management, Sonipat, Haryana 131028, India.
R-(+)-limonene (d-limonene) is a commonly used flavor additive in food, beverages and fragrances for its pleasant lemon-like odor. Considering its increasing applications, it's necessary to understand toxicological effects and risk associated with its use. R-(+)-limonene is rapidly absorbed in experimental animals and human beings following oral administration.
View Article and Find Full Text PDFR-Limonene metabolism in humans and metabolite kinetics after oral administration.
Arch Toxicol
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Institute and Outpatient Clinic of Occupational, Social and Environmental Medicine, Friedrich-Alexander Universität Erlangen-Nürnberg, Schillerstrasse 25/29, 91054, Erlangen, Germany.
We studied the R-limonene (LMN) metabolism and elimination kinetics in a human in vivo study. Four volunteers were orally exposed to a single LMN dose of 100-130 µg kg bw. In each case, one pre-exposure and subsequently all 24 h post-exposure urine samples were collected.
View Article and Find Full Text PDFD-Limonene modulates T lymphocyte activity and viability.
Cell Immunol
September 2012
Department of Biology, Lebanon Valley College, Annville, PA 17003, United States.
d-Limonene, a cyclic terpene that is a major component of several plant essential oils, is used widely as an additive in perfumes, soaps, foods and beverages, and has also been shown to possess chemopreventative and chemotherapeutic activity. A limited number of studies have been conducted investigating the effect of d-limonene on immune system function. We show that d-limonene and its metabolites limonene-1-2-diol and perillic acid inhibit the production by CD3(+)CD4(+) T cells of IFN-γ, IL-2, TNF-α, IL-4 and IL-13, and the production by CD3(+)CD8(+) T cells of IFN-γ, IL-2, and TNF-α.
View Article and Find Full Text PDFBiotransformation of limonene by bacteria, fungi, yeasts, and plants.
Appl Microbiol Biotechnol
May 2003
Institute of Biotechnology, ETH Hönggerberg, HPT, 8093 Zürich, Switzerland.
The past 5 years have seen significant progress in the field of limonene biotransformation, especially with regard to the regiospecificity of microbial biocatalysts. Whereas earlier only regiospecific biocatalysts for the 1,2 position (limonene-1,2-diol) and the 8-position (alpha-terpineol) were available, recent reports describe microbial biocatalysts specifically hydroxylating the 3-position (isopiperitenol), 6-position (carveol and carvone), and 7-position (perillyl alcohol, perillylaaldehyde, and perillic acid). The present review also includes the considerable progress made in the characterization of plant P-450 limonene hydroxylases and the cloning of the encoding genes.
View Article and Find Full Text PDFPhase I and pharmacokinetic study of D-limonene in patients with advanced cancer. Cancer Research Campaign Phase I/II Clinical Trials Committee.
Cancer Chemother Pharmacol
July 1998
Department of Medical Oncology, Charing Cross Hospital, London, UK.
Purpose: D-Limonene is a natural monoterpene with pronounced chemotherapeutic activity and minimal toxicity in preclinical studies. A phase I clinical trial to assess toxicity, the maximum tolerated dose (MTD) and pharmacokinetics in patients with advanced cancer was followed by a limited phase II evaluation in breast cancer.
Methods: A group of 32 patients with refractory solid tumors completed 99 courses of D-limonene 0.
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