<i>d</i>-Limonene challenging anti-inflammatory strategies

Patrizia A d'Alessio; Marie C Béné; Chantal Menut; Patrizia A d'Alessio; Marie C Béné; Chantal Menut

doi:10.3934/molsci.2022003

AIMS Molecular Science

2022, Volume 9, Issue 2: 46-65. doi: 10.3934/molsci.2022003

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Research article

d-Limonene challenging anti-inflammatory strategies

1.
AISA Therapeutics, University Paris Sud-11 and Genopole, Evry, France
2.
Hematology Biology, CHU de Nantes & Inserm 1232 CRCINA, Nantes, France
3.
IBMM, Univ Montpellier, CNRS, ENSCM, Montpellier, France

Received: 12 November 2021 Revised: 09 January 2022 Accepted: 07 April 2022 Published: 20 April 2022

Aging and senescence seem linked by fundamental, yet still ill-understood mechanisms. For this reason, this paper expands on the background of a discovery that still has to gain acknowledgement by public policies to find its place in a market hungry for a non-toxic anti-inflammatory molecule. Reversibility of the senescent cell phenotype was the starting-point of a research that turned out to identify the monoterpenes class of molecules as able to achieve this goal. Indeed, these compounds strongly inhibit the circulation of pro-inflammatory cytokines as well as the expression of cell-anchored adhesive molecules, liable to recruit activated immune cells. Starting from cell-based studies, the pre-clinical and clinical assays reported here confirmed the capacities of these compounds, both in experimental colitis, dermatitis and stress murine models, but also in-human studies addressing the latent chronic inflammation associated with age or psoriasis. Last but not least, because of an intriguing mechanism yet not totally unraveled and most probably depending on the effect of monoterpenes on gut microbiota strains–apart from assuring a constant gut barrier repair-a consistent Quality of Life amelioration, i.e. mood modulation probably due to enhanced dopamine secretion was also demonstrated. Finally, after entering in more pharmacologic considerations on toxicity and bio-availability studies as for the safety of this class of compounds, a strategic positioning of the precious role of anti-inflammatory drugs in a market that has yet to overcome common chronic diseases because of their predisposing condition not only to cancer and neuro-degenerative diseases but now also to COVID-19 is envisioned.
- drug discovery,
- anti-inflammatory molecules,
- monoterpenes,
- d-Limonene,
- common chronic diseases,
- aging,
- cell senescence
Citation: Patrizia A d'Alessio, Marie C Béné, Chantal Menut. d-Limonene challenging anti-inflammatory strategies[J]. AIMS Molecular Science, 2022, 9(2): 46-65. doi: 10.3934/molsci.2022003

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Abstract

Aging and senescence seem linked by fundamental, yet still ill-understood mechanisms. For this reason, this paper expands on the background of a discovery that still has to gain acknowledgement by public policies to find its place in a market hungry for a non-toxic anti-inflammatory molecule. Reversibility of the senescent cell phenotype was the starting-point of a research that turned out to identify the monoterpenes class of molecules as able to achieve this goal. Indeed, these compounds strongly inhibit the circulation of pro-inflammatory cytokines as well as the expression of cell-anchored adhesive molecules, liable to recruit activated immune cells. Starting from cell-based studies, the pre-clinical and clinical assays reported here confirmed the capacities of these compounds, both in experimental colitis, dermatitis and stress murine models, but also in-human studies addressing the latent chronic inflammation associated with age or psoriasis. Last but not least, because of an intriguing mechanism yet not totally unraveled and most probably depending on the effect of monoterpenes on gut microbiota strains–apart from assuring a constant gut barrier repair-a consistent Quality of Life amelioration, i.e. mood modulation probably due to enhanced dopamine secretion was also demonstrated. Finally, after entering in more pharmacologic considerations on toxicity and bio-availability studies as for the safety of this class of compounds, a strategic positioning of the precious role of anti-inflammatory drugs in a market that has yet to overcome common chronic diseases because of their predisposing condition not only to cancer and neuro-degenerative diseases but now also to COVID-19 is envisioned.

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