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Objectives: I evaluated whether a mixture of nicotinamide, vitamin C, and PDRN (NVP-mix) decreased melanogenesis by modulating mitochondrial oxidative stress and NNT expression in UV-B-irradiated animals and in an in vitro model of melanocytes treated with conditioned media (CM) from UVB-irradiated keratinocytes. Thus, I planned this study to clinically apply anti-melanogenesis proven material to patients with melasma and PIH.Based on this study, I am clinically applying it to existing whitening treatments such as micro-needle RF and 1064nm Q-switch laser toning. Introduction: Nicotinamide nucleotide transhydrogenase (NNT) is involved in decreasing melanogenesisnthrough tyrosinase degradation induced by cellular redox changes., Nicotinamide nucleotide transhydrogenase (NNT) was recently shown to be involved in melanin synthesis in the skin. ctive oxygen species (ROS)-induced injury. NNT induces cellular redox changes that lead to tyrosinase degradation and melanosome maturation modulation to decrease eumelanin levels.Vitamin C and polydeoxyribonucleotide (PDRN) are also known to decrease skin pigmentation. Materials / method: We evaluated whether NVP-mix modulated NNT in UV-B-irradiated animal skin. The expression levels of NNT in the epidermal tissues of the control animals (controlgroup), UV-B-irradiated animals (UV group), and NVP-mix-applied UV-B-irradiated animals(UV/NVP group) were compared. Notably, the mice in the UV group and UV/NVP group were exposed to UV-B irradiation every 2 days until the end of the experiment. Fifteen days after the start of the experiment, the UV/NVP group was administered 50 µL of NVP-mix per square centimeter of skin at 7-day intervals via a microneedle therapy system (MTS). Results: The expression of NNT in the epidermises of the animals in the UV group was significantly lower than that in the control group, whereas the expression of NNT in the UV/NVP group was significantly higher than that in the UV group. The GSH/GSSG ratio in the mitochondria from the skins of the animals in the UV group was significantly lower than that in the control and UV/NVP groups. The mitochondrial NADPH/NADP+ ratio in the skins of the mice in the UV group was significantly lower than that found in the control and UV/NVP groups. Conclusion: In conclusion, NVP-mix decreased mitochondrial oxidative stress by increasing NNT expression and decreased melanogenesis by decreasing MC1R/MITF, tyrosinase, TYRP1, and TYRP2. NVP-mix decreased melanogenesis signals, such as MC1R, MITF, TYRP1, and TYRP2, and decreased melanosome transfer-related signals, such as RAB32 and RAB27A, in UV-B-irradiated animal skin. NVP-mix also decreased MC1R, MITF, TYRP1, TYRP2, RAB32, and RAB27A in melanocytes treated with CM from UV-irradiated keratinocytes.