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Anti-stress effects of d-Limonene and its metabolite perillyl alcohol

d'Alessio PA - Bisson JF - Bene MC - 2013 Rejuvenation Res
University Paris Sud 11, Cell Biology, Biopark CAmpus CAncer, Villejuif, France, 94807, AISA Therapeutics, Genopole, 4, rue Pierre Fontaine, EVRY, France, 91058 ; endocell@wanadoo.fr.

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, liable to disrupt the ortho / parasympathetic balance essential for a harmonious life. Proper nutrition and adequate physical activity, by limiting the harmful influence of stress, play important roles to avoid developing disease and to promote healthy aging. d-Limonene, a monoterpene shown to reduce inflammatory parameters in several pre-clinical and clinical models, could also develop 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, submitting animals to non-pathological stress. d-Limonene or its metabolite perillyl alcohol (POH) were administered per os at a dose of 10mg/kg. FOB tests were performed one hour before gavage then at 60, 120 and 180 minutes. 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 sings 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 for d-Limonene as diet supplement could thus be claimed as an anti-stress substance.

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