Lemon Balm (Melissa officinalis L.) Leaf Extract Promotes Endo180 Production in Dermal Fibroblasts and has Antiwrinkle Effect on Human Skin

BACKGROUND: The collagen receptor Endo180 participates in extracellular matrix remodeling by clearing the pericellular environment and recognizing and internalizing collagen degradation products. In photoaged skin, Endo180 expression in fibroblasts is decreased, and collagen fragments accumulate in the pericellular environment, leading to a decrease in type I collagen production and an increase in matrix metalloproteinase 1 production. This suggests that a decrease in Endo180 production may promote wrinkle formation by decreasing the dermal collagen fibril volume. Therefore, this study aimed to identify materials that promote Endo180 production in vitro and investigate whether promoting Endo180 production could prevent and improve wrinkles in vivo. METHODS: Endo180 gene expression and protein production in fibroblasts were evaluated after screening 71 natural extracts. The conditioned medium of UVB-irradiated keratinocytes and Endo180 production-promoting extract were added to fibroblasts, and Endo180 and type I collagen production were evaluated. In a double-blind, randomized, placebo-controlled study, a cream formulated with an Endo180 production-promoting extract or placebo was topically administered to each side of the face of 20 healthy women twice daily for 8 weeks. RESULTS: Screening results showed that 50 μg/mL of lemon balm (Melissa officinalis L.) leaf extract (MOLE) resulted in the highest levels of both Endo180 mRNA and protein at 178.1% and 127.4%, respectively. Its major component rosmarinic acid also promoted Endo180 production by 143.9% at a concentration of 20 μg/mL. MOLE at 200 μg/mL almost completely inhibited the decrease in Endo180 and type I collagen production in UVB-irradiated keratinocyte-conditioned medium. Furthermore, eye-corner wrinkles were reduced by treatment with the MOLE formulation compared to that in response to the placebo formulation. CONCLUSIONS: MOLE may act as an antiwrinkle agent that inhibits the decline in collagen levels by promoting Endo180 production.