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Maintaining a youthful appearance is a common desire among the aging population. Loss of elasticity and dermal density constitutes major causes of wrinkle formation during skin aging. In particular, periorbital wrinkles comprise the critical assessment point of skin aging. To address these issues, cosmetic industries have been making increasing efforts to develop efficient agents against wrinkle formation. Arg-Gly-Asp (RGD) is a tripeptide sequence used for surface coating because of its integrin-binding property. However, its pharmacological properties on skin have not yet been studied. Here, we synthesize the novel palmitoyl-Arg-Gly-Asp (Palm-RGD) and investigate its effects on periorbital wrinkle formation by clinical and in vitro studies. We observed that Palm-RGD cream application for 12 weeks decreased global photodamage and skin roughness (R1, R2, R3, and Ra) scores without causing skin irritation. In addition, topical application of Palm-RGD cream time-dependently increased skin elasticity and dermal density. An in vitro study using human dermal fibroblasts (HDFs) demonstrated increased type I procollagen production by Palm-RGD treatment. Furthermore, Palm-RGD suppressed MMP-1 expression in HDFs. Our results demonstrate that Palm-RGD has protective effects against wrinkle formation, likely through the activation of collagen expression and the protection against collagen degradation. Therefore, Palm-RGD could be used as a potential agent for the prevention of wrinkle formation consequent to aging. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Perilla frutescens (L.) Britt. (Lamiaceae) is a traditional herb that is consumed in East Asian countries as a traditional medicine. This traditional herb has been documented for centuries to treat various diseases such as depression, allergies, inflammation and asthma. However, the effect of Perilla frutescens on skin has not been characterized well. Aim of the study The present study aimed to investigate the effect of Perilla frutescens leaves extract (PLE) on ultraviolet radiation-induced extracellular matrix damage in human dermal fibroblasts and hairless mice skin. Materials and methods Human dermal fibroblasts and Skh-1 hairless mice were irradiated with UV and treated with PLE. Protein and mRNA levels of various target molecules were analyzed by western blotting and quantitative RT-PCR, respectively. Histological changes of mouse skin were analyzed by H&E staining. To elucidate underlying mechanism of PLE, activator protein-1 (AP-1) DNA binding assay and the measurement of reactive oxygen species (ROS) were performed. Results PLE significantly inhibited basal and UV-induced MMP-1 and MMP-3 expression dose-dependently, and also decreased UV-induced phosphorylation of extracellular signal-regulated kinases and c-Jun N-terminal kinases. This inhibitory effects of PLE on MMP-1 and MMP-3 were mediated by reduction of ROS generation and AP-1 DNA binding activity induced by UV. Furthermore, PLE promoted type I procollagen production irrespective of UV irradiation. In the UV-irradiated animal model, PLE significantly reduced epidermal skin thickness and MMP-13 expression induced by UV. Conclusion Our results demonstrate that PLE has the protective effect against UV-induced dermal matrix damage. Therefore, we suggest that PLE can be a potential agent for prevention of skin aging. [ABSTRACT FROM AUTHOR]