AISA can control the inflammatory facet of SASP
Patrizia A d’Alessio, Jean-François Bisson, Valeria M Ursini, Marie C Béné
Pr Dr Patrizia D'ALESSIO MD PhD University Paris Sud-11 and Biopark Cancer Campus 1, mail Pr Georges Mathé 94807 Villejuif France
Background
Senescence is a natural phenomenon, inducing the arrest of cell proliferation after reaching specific checkpoints, which controls the programmed number of divisions inherent to each cell-type. Accelerated by various types of stress, senescence is associated to inflammation and more specifically chronic inflammation. Moreover, senescent cells themselves develop a specific secretion profile promoting inflammation (SASP). Sustained inflammation, intrinsically deleterious on the microenvironment, moreover can induce modifications of stem cells and their niches, leading to a decreased potential of tissue regeneration. Both stress and inflammation are involved in the generation of cell senescence in vitro and in vivo. This translates, among other effects, in an increased expression of adhesion molecules, notably on endothelial cells, thereby increasing diapedesis and maintaining chronic
inflammation. Concomitantly, stressed/senescent cells display an increased actin polymerization limiting their plasticity.
Methods and Results
Monoterpenes have long been shown to display relaxing and antitumoral effects, thus limiting stress and thereby the risk to develop cancer. We have demonstrated that Anti-Inflammatory Senescence Actives (AISA) of natural origin, and notably d-Limonene present at high concentration in orange peel extracts, exert significant anti-stress and anti-inflammatory properties. Indeed, in animal and human models, this monoterpen decreases systemic levels of such pro-inflammatory cytokines as TNF-alpha and IL-6. In vitro, these cytokines activate the NF-κB pathway, which can therefore be inhibited by d-Limonene. In view of the large
implication of this pathway in major cellular activities, it is likely that AISA may display a wide range of beneficial effects in the field of chronic inflammation. Indeed, both in vitro and in vivo, d-Limonene has been demonstrated to inhibit the NF-κB dependent expression of adhesion molecules on endothelial cells. Furthermore, d-Limonene significantly interferes with actin polymerization leading to reverse F-actin fibers into G-actin monomers.
Conclusion
From these studies, it appears that AISA, and especially d-Limonene, a non-toxic monoterpene with anti-inflammatory and anti-tumoral properties, are able to control a number of related cell-mechanisms involved in cell senescence, including a reduction of SASP production.
References
Oral administration of d-Limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet
supplementation in humans. PA. d'Alessio, R Ostan, J-F Bisson, JD. Schulzke, MV. Ursini, MC. Béné, Life Sciences, 92 :1151-
56, 2013.
Skin repair properties of Perillyl Alcohol in murine models. PA. d'Alessio, M Mirshahi, J-F Bisson, MC. Béné, Anti-Inflammatory
& Anti-Allergy Agents in Medicinal Chemistry, (1) : 29-35, 2014.
Impact of diet and nutraceutical supplementation on inflammation in elderly people. Results from the RISTOMED study, an
open-label randomized control trial. Ostan R, Béné MC, Spazzafumo L, Pinto A, Donini L, Pyren F, Charrouf Z, Valentin L,
Lochs H, Bourdel-Marchasson I, Blanc-Bisson C, Buccolini F, Brigidi P, d’Alessio PA. Clin Nutr. 35 (4) : 812-8, 2016.
Pr Dr Patrizia D'ALESSIO MD PhD University Paris Sud-11 and Biopark Cancer Campus 1, mail Pr Georges Mathé 94807 Villejuif France
Background
Senescence is a natural phenomenon, inducing the arrest of cell proliferation after reaching specific checkpoints, which controls the programmed number of divisions inherent to each cell-type. Accelerated by various types of stress, senescence is associated to inflammation and more specifically chronic inflammation. Moreover, senescent cells themselves develop a specific secretion profile promoting inflammation (SASP). Sustained inflammation, intrinsically deleterious on the microenvironment, moreover can induce modifications of stem cells and their niches, leading to a decreased potential of tissue regeneration. Both stress and inflammation are involved in the generation of cell senescence in vitro and in vivo. This translates, among other effects, in an increased expression of adhesion molecules, notably on endothelial cells, thereby increasing diapedesis and maintaining chronic
inflammation. Concomitantly, stressed/senescent cells display an increased actin polymerization limiting their plasticity.
Methods and Results
Monoterpenes have long been shown to display relaxing and antitumoral effects, thus limiting stress and thereby the risk to develop cancer. We have demonstrated that Anti-Inflammatory Senescence Actives (AISA) of natural origin, and notably d-Limonene present at high concentration in orange peel extracts, exert significant anti-stress and anti-inflammatory properties. Indeed, in animal and human models, this monoterpen decreases systemic levels of such pro-inflammatory cytokines as TNF-alpha and IL-6. In vitro, these cytokines activate the NF-κB pathway, which can therefore be inhibited by d-Limonene. In view of the large
implication of this pathway in major cellular activities, it is likely that AISA may display a wide range of beneficial effects in the field of chronic inflammation. Indeed, both in vitro and in vivo, d-Limonene has been demonstrated to inhibit the NF-κB dependent expression of adhesion molecules on endothelial cells. Furthermore, d-Limonene significantly interferes with actin polymerization leading to reverse F-actin fibers into G-actin monomers.
Conclusion
From these studies, it appears that AISA, and especially d-Limonene, a non-toxic monoterpene with anti-inflammatory and anti-tumoral properties, are able to control a number of related cell-mechanisms involved in cell senescence, including a reduction of SASP production.
References
Oral administration of d-Limonene controls inflammation in rat colitis and displays anti-inflammatory properties as diet
supplementation in humans. PA. d'Alessio, R Ostan, J-F Bisson, JD. Schulzke, MV. Ursini, MC. Béné, Life Sciences, 92 :1151-
56, 2013.
Skin repair properties of Perillyl Alcohol in murine models. PA. d'Alessio, M Mirshahi, J-F Bisson, MC. Béné, Anti-Inflammatory
& Anti-Allergy Agents in Medicinal Chemistry, (1) : 29-35, 2014.
Impact of diet and nutraceutical supplementation on inflammation in elderly people. Results from the RISTOMED study, an
open-label randomized control trial. Ostan R, Béné MC, Spazzafumo L, Pinto A, Donini L, Pyren F, Charrouf Z, Valentin L,
Lochs H, Bourdel-Marchasson I, Blanc-Bisson C, Buccolini F, Brigidi P, d’Alessio PA. Clin Nutr. 35 (4) : 812-8, 2016.
