Solar lentigo represent one of the most visible signs of photoaging reported on a majority of elderly people, increasing with age, the degree of exposure to UV and pollution. Epigenetic regulation is currently the most studied adaptive response to fight against skin pigmentation caused by UV exposure
To reduce the appearance of UVB-induced pigmented spots, the goal of our study was to identify a specific microRNA (miR) targeting the tyrosinase, one of the key enzymes involved in the production of melanin by melanocytes. However, to reach clinical efficacy, we aim to identify a unique low-redundant miR whose defect would not be counterbalanced by other miRs.
We used bioinformatic strategies to virtually select miRs targeting the 3’-UTR regulation rather than the 5’-UTR coding sequence of TYR mRNA for a higher inhibition, and with at least a 7-Mer hybridization potential within the seed sequence to have a strong miR/TYR mRNA interaction. The functional miR was confirmed using miR mimic transfection and western blot and the UVB regulation study was performed by q-RTPCR. We selected a miR stimulator/TYR inhibitor ingredient in Asian melanocytes and Asian melanocytes-keratinocytes coculture. The spot’s area and melanin content were finally evaluated by image analysis on Chinese people (18-60 yo) having pigmented-spot and living in a sunny and daily air-traffic polluted environment (3% ingredient vs placebo and 2% AA2G).
We identified the miR-490-3p. After exposure to UVB (25 mJ/cm2) this miR was decreased by 29% and its mimic reduced by 50% TYR protein production. We selected a Lansium domesticum leaf extract stimulating miR-490-3p expression by 40% and decreasing TYR protein synthesis in melanocytes (33%), melanin content in cocultures (34%), surface and melanin content of pigmented spots (respectively 18% and 16% at 0.3% vs placebo, significantly better than 2% AA2G).
We demonstrated in silico, in vitro and in vivo that specific targeting of the less redundant and functionally proven miR-490-3p is a novel and precise epigenetic way to efficiently reduce the pigmented spots.

Epigenetic mechanism linked to pigmented spots explored by in silico, in vitro and in vivo methods