Inhibition of Melanin Synthesis and Inflammation by Exosomes Derived from Leuconostoc mesenteroides DB-14 Isolated from Camellia japonica Flower.

Leuconostoc mesenteroides is a lactic acid bacteria found in fermented products. In our previous study, L. mesenteroides was isolated from Camellia japonica flowers, and its acid tolerance and antibacterial properties were thoroughly investigated. This study focuses on the inhibition of melanin synthesis and inflammation of exosomes derived from L. mesenteroides. Moreover, L. mesenteroides exosomes (DB-14 exosome) exhibited significant inhibitory effects on inflammation and melanogenesis. At concentrations of 4.44 × 10⁸, 8.88 × 10⁸, and 1.78 × 10⁹ particles/ml, the exosomes reduced nitric oxide and prostaglandin E2 activity while maintaining the growth of RAW 264.7 macrophages. In addition, proinflammatory cytokines, such as interleukin (IL)-1β, IL-6, and tumor necrosis factor alpha, were rarely expressed, and western blot revealed that L. mesenteroides DB-14 derived exosomes inhibited inducible nitric oxide synthase and cyclooxygenase-2 expression. Moreover, the exosomes had no toxic effects on B16F10 melanoma cells at concentrations of 1.78 × 10⁹, 3.55 × 10⁹, and 7.10 × 10⁹ particles/ml, and they suppressed melanogenesis by reducing tyrosinase activity. Furthermore, western blot analysis demonstrated that microphthalmia-associated transcription factor (MITF), tyrosinase, tyrosinase related protein (TRP)-1, and TRP-2 were evidently reduced, ultimately repressing melanin production. Moreover, MITF expression was inhibited by reduced mitogen-activated protein kinase and protein kinase B phosphorylation levels. Overall, this study proves the efficacy of the novel DB-14 exosome as a strong lightening and anti-inflammatory agent.