title: Anti-stress effects of d-limonene and its metabolite perillyl alcohol.
abstract: Stress is closely linked by its biological mechanisms to inflammation and by its consequences to accelerated aging. Stress triggers a hormonal response along the hypothalamus-pituitary-adrenal (HPA) axis, which can disrupt the ortho/parasympathetic balance essential for a harmonious life. Proper nutrition, adequate physical activity, and limiting the harmful influence of stress play important roles in avoiding the development of disease and promoting healthy aging. d-Limonene, a monoterpene shown to reduce inflammatory parameters in several pre-clinical and clinical models, could also produce an anti-stress action by altering ortho/parasympathetic parameters as well as central neurotransmitter functions. Here we report on a rat model, where a functional observational battery (FOB) was performed by submitting animals to non-pathological stress. d-Limonene or its metabolite perillyl alcohol (POH) were administered per os at a dose of 10 mg/kg. FOB tests were performed 1 hr before gavage and then at 60, 120, and 180 min. These tests confirmed the stressed status of control rats fed vehicle. Conversely, a series of parameters were significantly less disturbed in treated rats, who retained a better activity and displayed less signs of stress. These effects were more pronounced and sustained after ingestion of d-limonene than POH, suggesting the role of endogeneous metabolization of the terpene. These studies show that d-limonene exerts, through its metabolite POH, a significant anti-stress action measurable by behavioral and physiologic parameters under the influence of the nervous system. In addition to its anti-inflammatory effects, a beneficial role as an anti-stress substance could thus be claimed for d-limonene used as a dietary supplement.
authors.affiliation: 1 Biopark Cancer Campus, University Paris Sud-11 , Villejuif, France .
authors.forename: Patrizia A
authors.initials: PA
authors.lastname: d'Alessio
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Bisson
authors.forename: Marie C
authors.initials: MC
authors.lastname: Béné
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D053138:Cyclohexenes / Q000494:pharmacology*; D005247:Feeding Behavior / Q000187:drug effects; D005260:Female; D000077222:Limonene; D039821:Monoterpenes / Q000378:metabolism* / Q000494:pharmacology*; D017208:Rats, Wistar; D013312:Stress, Physiological / Q000187:drug effects*; D013729:Terpenes / Q000494:pharmacology*; D013997:Time Factors
chemical_list: D053138:Cyclohexenes; D039821:Monoterpenes; D013729:Terpenes; C032208:perillyl alcohol; D000077222:Limonene