Title : Control of melanocyte senescence and environmental niche for reducing appearance of lentigo and hypomelanotic macule side effects
Abstract:
Ageing and repeated sun exposure increase formation of oxidising radicals that randomly attack lipids, proteins, and DNA of skin tissue and cells, leading to premature ageing and cell death. Chronic damage such as accumulation of mutations into melanocytes drives their senescence altering their physiology and the regulation of melanin production that either goes into overdrive (lentigo) or conversely, stops (hypomelanotic macula). Lentigos are highly visible dark macules whose number and size increase with age. Fading out these hyper melanotic spots, is essential because they strongly impact skin appearance making it look older than it really is. Hypomelanotic spots also increase with age and sun exposure. Less apparent than lentigos, they result from a progressive senescence of melanocytes and their death. They create a circular depression with a smooth bottom and no apparent pigment, due to the UV-damage on underlying extracellular matrix. For both spots, reducing radical oxygen species’ (ROS) consequences and formation of senescence are pivotal as well as protection of the melanocyte niche composed of neighbouring keratinocytes, fibroblasts, and extracellular matrix. Chemical peels, laser therapy, retinoids or corticoids are often proposed to solve these unsightly spots but can be damageable for skin or invasive. Some plant extracts are well known for their protective role versus ROS. Monarda didyma leaf cell culture extract (MDL), obtained by a new and safe way of production, rich in polyphenols such as rosmarinic acid and prunin, was shown to control ROS production into melanocytes, singlet oxygen formation and lipid peroxidation. It also protects the niche of melanocyte in moderating matrix proteases’ synthesis (elastase, MMP-2 and -3) by fibroblasts whereas it triggers hyaluronan, collagen-I, -IV, -VII and -XVII productions into keratinocytes and skin explants. MDL strongly moderates activity of the Senescence Associated-?-Galactosidase into melanocytes. It reduces interleukin-6 and -8, part of the so called SASP (Senescence Associated Secretory Phenotype), it preserves dendrites shape and numbers, and it reduces Dickkopf-1 protein production, all of which are characteristic of senescence. Clinical studies performed on 52 volunteers, for two months, versus a placebo control, indicated that MDL significantly reduces dark spot pigmentation and skin pigmentation heterogeneity while it improves complexion evenness. In parallel, volume and depth of hypomelanotic spots are reduced while skin flexibility and elasticity are significantly improved versus placebo. Our results indicate that the improvement of unsightly characteristics of both dark and hypomelanotic spots can be obtained in controlling ROS productions and senescence of melanocytes. Furthermore, in addition to a direct action on this cell type, it seems of interest to improve its microenvironment for a better control of its homeostasis, melanin production and secretions.
Audience Take Away Notes:
- This work highlights the interest of the niche of the melanocyte as an important actor of its physiology and pathology
- The audience will be able to design new products to offer to their customers: Innovative and noninvasive solutions to sun related pigmentary disorders. Plant cell cultures are innovative, sustainable and safe way to produce cosmetic ingredients
