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mechanisms, such as: Aquaporin-3, a transmembrane protein that allows transportation of water and glycerol inside the cell and plays a role in maintaining epidermal hydration;
Nrf2 factor that triggers one of the most well-known skin detoxification pathway, and protects the cells against oxidative stress.
But an intense and stressful lifestyle, jet- lag, shift work, or blue light emitted by screens, can disrupt this rhythm. Under the action of these stress factors, the circadian genes undergo modifications in their phase and amplitude: the rhythm is dysregulated, and the biological functions that rely on the circadian rhythm are affected (Fig 2). As a consequence, aquaporin-3 is not able to maintain a correct cell homeostasis. And the Nrf2 pathway becomes less efficient in eliminating Reactive Oxygen Species (ROS) to detoxify the skin. The concentration of free radicals increases causing cellular damages. Skin wellbeing is affected by these phenomena. In addition, blue light emitted by screens generates additional oxidative stress which also affects skin homeostasis and therefore skin quality. As a result, desynchronised skin becomes more prone to aggressions, becomes dull and shows signs of fatigue.
Figure 2: Impact of modern lifestyle stress on skin circadian rhythm synchronisation.
passing by. While others, called Bmal-1 and Clock, are at their highest level of expression in the evening, and decrease afterwards during the night. This molecular mechanism that governs the circadian rhythm has been deeply studied by a team of Swedish research scientists, which earned them the Nobel Prize in Medicine or Physiology in 2017. This major breakthrough showed the fundamental role of the circadian rhythm in the body balance and therefore in the skin balance, which is directly linked to its wellbeing. Indeed, it has been demonstrated that circadian rhythm plays a key role in the expression of several other genes, which explains why a number of major biological functions follow this 24- hour rhythm. As an example, during the day skin cells express genes implicated in protection mechanisms against environmental aggressions, such as UV rays. At night, the cells will express genes whose roles are to repair DNA and other cellular damages that have occurred during the
April 2019
day. In our body, more than 40% of the proteins follow a circadian rhythm is characterised by two main parameters, its phase and its amplitude (Fig 1). The phase corresponds to the oscillation frequency of a gene expression. In a normal cycle, a gene recovers the same level of expression every 12 hours, which corresponds to the night and day cycles. The amplitude is the difference between the highest and the lowest expression level, going around a basal level for each gene.
If the phase and/or the amplitude differ
from their standard values, the circadian rhythm is desynchronised. The cell does not follow the night and day cycle any more, and its biological functions are degraded.
A dysregulated circadian rhythm can alter skin biological functions and affect its appearance Many studies have demonstrated the importance of a stable, or synchronised, circadian rhythm in order to maintain the proper function of key biological
Taking inspiration from plants to resynchronise skin The circadian rhythm is also implicated in the natural rhythm of the plants, which explains why leaves and flowers open out during the day and close at night. The ingredient developed has been inspired by this natural ability and transposed to the skin, and obtained from an extract of Lespedeza capitata, a plant growing wild and collected in South Korea, a country known for its remarkable biodiversity. As a medicinal plant part of the homeopathic medicine, it contains two key active molecules from the flavonoids family: carlinoside and isoshaftoside, directly involved in circadian rhythm maintenance.
Unique model of synchronised skin To demonstrate the ability of the Lespedeza capitata extract to resynchronise the circadian rhythm, a unique model of synchronised skin has been developed. A skin explant has been exposed to dexamethasone, a known synchroniser able to set the cells in the same phase. The explant, whether or not in the presence of the active, has then been exposed to blue light radiations in order to disrupt its circadian rhythm. After 24 h and 36 h, in order to study a complete night and day cycle, various markers expressed in the morning or in the evening have been observed: Per-2/Cry-1 and B-mal-1 (Fig 3).
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