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ANTI-POLLUTION 29


Schisandra chinensiscombats pollution-induced stress


n Carine Boutot, Edwige Ranouille, Emilie Bony, Jean-Yves Berthon, Edith Filaire – Greentech, France Claire Leduc – Synthivia, France Philippe Bedos – Synthivia & CIAMS, France


Atmospheric pollution, which contains a quantity of microscopic suspended particulate matter (PM) carrying various toxic chemical molecules, including polycyclic aromatic hydrocarbons (PAHs), has to be considered nowadays as one of the main characteristics of areas where, worldwide, human population density is at a high level. It affects many rural, industrial, and urban sites1


and has been recognised


as the most important environmental health issue in the world. However, few studies concern the impact of air pollution and PM on skin integrity, even if it has been shown that they are significantly associated with weakened barrier function, oxidative stress, skin diseases, and skin ageing.2


PM


penetrate skin either through hair follicles or transdermally, and exert its detrimental effects through the generation of reactive oxygen species (ROS), which contributes to extrinsic skin ageing. ROS activate the mitogen-activated protein kinase (MAPK) signaling pathway inducing metalloproteinases (MMPs) production which are closely related to inflammatory skin diseases and skin ageing (Fig 1).1 PAHs and PM are also well established to activate the aryl hydrocarbon receptor (AhR), a pollutant sensor that constitutes the starting point of the detoxification mechanism, by upregulating the transcription of responsive genes, such as cytochrome P450 superfamily. However, these activations generate ROS. Endogenous defense mechanisms including a fundamental biochemical pathway nuclear factor erythroid 2–related factor 2 (Nrf2) is activated in order to fight the deleterious effects of all pollutants on skin. It is able to help eliminate and inactivate exogenous toxic agents by fundamental biological pathways closely interconnected. Nrf2 is constitutively expressed in the cytoplasm, and its accumulation and activation in the nucleus are favoured in oxidative injury. Additionally, Nrf2 is stabilised by the Parkinson’s-associated protein, (DJ-1),


November 2018 Abstract


The human skin, and mainly the upper layer of the epidermis, plays the role of a barrier, but is also one of the first and major targets of air pollutants, pollutants contributing to wrinkle and dark sports occurrence through the redox imbalance. A possible approach to attack ROS-mediated disorders for both preventive and treatment means is based on the use of substances, which can be found in plants as secondary metabolites, lignans being a promise candidate. The present study was aimed to better understand the cellular mechanisms beyond the oxidative changes induced by urban pollution (Urban dust 1649b, NIST) and the effect of Schisandra chinensis (S. chinensis) extract in reconstructed human epidermis, by a transcriptomic approach and secondly through the evaluation of Nrf2, AhR, NF-kB, and DJ-1pathways using an in vitro model. Finally, we evaluated the effect of S. chinensis on skin hydration, homogeneity, radiance and luminosity in Chengdu (China). Urban dust (80µg.mL-1


) was able to activate the


cytoplasmic expression of NF-kB and AhR when compared to control. S.chinensis extract attenuated the urban dust-induced oxidative stress, the protective mechanism being associated, at least in part, with the modulation of the Nrf2 and AhR pathways and the activation of DJ-1. S. chinensis extract, named Urbalys®


protects from


prolonged pollution aggression since it improves hydration, protects skin homogeneity, increases skin radiance and attenuates skin spot intensity after 21 days of pollution exposition.


a multifunctional protein expressed in almost all tissues involved in various physiological processes such as transcriptional regulation, anti-oxidative stress reaction, mitochondrial regulation, and signal transduction (Fig 1).3


More


precisely, DJ-1 promotes Nrf2 binding to antioxidant response elements by which Nrf2 can regulate the expression of several endogenous antioxidative enzymes and reduce ROS production to protect mitochondria and can also respond to oxidative stress. Under oxidative stress, DJ-1 plays critical antioxidant defence roles by several molecular processes. Additionally, it protects mitochondria by directly maintaining mitochondrial complex I activity and translocating into mitochondria as an endogenous antioxidant.4


A possible approach to attack ROS- mediated disorders for both preventive and treatment means is based on the use of substances which can be found in plants as secondary metabolites. Various phytochemicals and herbal extracts exert


their antioxidant properties by activating the Nrf2 system. Schisandra chinensis is a traditional Chinese herbal medicine that has been used for the treatment in Asia for thousands of years. The lignans as the main active ingredients in S. chinensis have various pharmacological effects such as anti-oxidative, anti-inflammatory, antitumor, and hepatoprotective activities. Schisandra extract also seems to inhibit IκB activation, thereby suppressing the production of TNF-α, IL-6.5 These findings led us to postulate that S. chinensis lignans might protect skin cell functions against urban pollution and could be used as cosmetic agents. Thus, the objective of this study was firstly to identify the effects of urban dust by a transcriptomic approach on reconstructed human epidermis and then the effect of urban dust and S. chinensis extract on the expression of genes involved in response on cellular protection mechanisms, namely the detoxification pathways. Secondly, we examined the effect of active extract from S. chinensis on the protection of human keratinocytes damages caused by pollution


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