Mela B3 (La Roche-Posay Laboratoire Dermatologique, Levallois, France) contains 2-MNG, LHA, 10% niacinamide, as well as other ingredients (Cystoseira tamariscifolia extract, retinyl palmitate, dipotassium glycyrrhizate, carnosine, capryloyl salicylic acid, hyaluronic acid and glycerin).

Clinical study 1 was a randomised controlled intra-individual study that included 32 healthy individuals. The study was approved by SGS ethics committee for clinical research (SS-2024-001S), and appropriate consent was obtained for studies involving human participants. Inclusion criteria included healthy male individuals or female individuals aged 18 to 60 years and individuals with an individual typology angle (ITA°) value of skin colour at the test site ranging from 20° to 41°. ITA°, or individual typology angle, is a parameter used to characterise human skin colour by measuring the skin’s L*a*b* values with a chromameter or diffuse reflectance spectrophotometer. An informed consent signature was required for all participants. Eligible subjects proceeded to the skin darkening model establishment phase on their back. First, the minimal erythema dose (MED) was determined for each subject’s test site (back area). The MED is the lowest UV dose (J/m2) or shortest exposure time (s) that produces clearly visible erythema covering most of the irradiated area. After selecting test areas within the sites, subjects received daily UV exposure at 0.75 MED using a solar simulator for four consecutive days. A 4-day post-irradiation period followed, without any intervention, allowing skin darkening to develop. On day 5 post-irradiation, visual and instrumental skin colour assessments were conducted and inconsistent test areas (ITA values deviating > 5 from the overall mean) were excluded. On the same day, test serum (2-MNG-containing serum), positive control (7% ascorbic acid) and negative control (vehicle) were randomly applied to the darkened test areas on their lower back (3 cm × 3 cm each, spaced > 1.0 cm apart), at a dose of 2.00 ± 0.05 mg/cm2. The test serum was applied twice daily (according to product usage instruction), with at least a 4-h interval between applications, while the positive control was applied once daily (refer to safety and technical standards for cosmetics). This regimen continued for 4 weeks, with visual and instrumental skin colour assessments performed at weeks 1, 2, 3 and 4. The evaluation was done by two independent dermatologists.

Clinical study 2 is an open label study approved by SGS ethics committee for clinical research (2024022). Informed consent was obtained for all participants. Healthy women aged 20–54 years presenting at least one uniform, clearly defined spot or post-acne mark on the face with a diameter of ≥ 3 mm and no pigmented spots on the adjacent skin (the number of participants with spots and post acne marks each account for 50%) were included. Participants had skin types I–VI with sun sensitivity, including all skin types (normal, oily, dry, combination); 50% of participants had sensitive skin. The study included a total of 63 healthy Chinese female individuals (52% self-claimed with sensitive skin). All completed the self-evaluation questionnaire, and only 42 completed clinical assessments. Participants were requested to apply the tested 2-MNG-containing serum twice a day for 56 days, along with a daily skin care routine including standard cleanser, standard cream and standard sunscreen that continued until the end of the study. Skin tone, skin colour and melanin content were measured during the 56 days of product usage, as well as 7 days after discontinuation; a questionnaire survey was provided to the 63 participants at the end of the study. Evaluations were performed at D0 (before use), D0Timm (15 min after first application), D7 (7 days after study start), D14, D28, D56 and D63 (7 days after the end of tested serum use). The evaluation was done by two independent dermatologists.

This study was conducted in accordance with the Declaration of Helsinki of 1964 and its subsequent amendments and followed the OECD Good Clinical Practice (GCP) guidelines. The study was approved by the SGS Clinical Research Ethics Committee (no. SS-2024-001S, 2024022). Written informed consent to participate in the study and for publication was provided by all patients.

Demographic and phenotypic characteristics were described as frequency (percent) or mean (± standard deviation (SD)) depending on the data type. Differences in classified variables or ranking variables between groups were assessed with Pearson chi-squared tests or Fisher’s exact tests. Normally distributed continuous variables were compared by t-test or Kruskal–Wallis one-way analysis of variance (ANOVA), with comparisons in non-normally distributed continuous variables performed using the Mann–Whitney U test or non-parametric ANOVA.

All of the analyses were conducted using Empower (R) (www.empowerstats.com, X&Y solutions, inc. Boston, Massachusetts) and the R statistical software package (http://www.R-project.org, R Foundation). If the data met normal distribution, the paired t-test method was used otherwise Wilcoxon sign rank test was used. Grade data were analysed with Wilcoxon sign rank test. Statistical significance was taken as a two-sided P-value < 0.05.