The dermal-epidermal junction (DEJ) provides a physical and biological interface between the epidermis and the dermis. In addition to providing a structural integrity, the DEJ also acts as a passageway for molecular transport. Based on the recently reported importance of the DEJ in skin aging, novel peptide derivatives have been tested for their effects on basement membrane (BM) protein expressions in cultured human epidermal keratinocytes. As a result, protein expressions of collagen XVII, laminin and nidogen were stimulated by the test peptide and peptides complex. Further ex vivo evaluation using excised human skin, confirmed that the topical application of the peptides complex significantly increased dermal collagen expression, as well as expressions of collagen XVII and laminin. Interestingly, while the origin of the laminin protein is epidermal keratinocytes, the immunohistochemical staining of skin showed that laminin was only detected in the uppermost layer of the dermis, which suggests a tight assembly of laminin protein onto the dermal side of the DEJ. These results suggest that a peptide complex could improve the structural properties of the DEJ through its ability to stimulate BM proteins. In order to evaluate the anti-wrinkle benefits of the peptide complex in vivo, a clinical study was performed on 22 healthy Asian female volunteers older than 40 years. As a result, significant improvements in skin wrinkles for all of the five sites were observed after two weeks, as assessed by skin topographic measurements. Collectively, these results demonstrate the anti-aging efficacy of the peptides complex.

Pollution-induced skin damage results in oxidative stress; cellular toxicity; inflammation; and, ultimately, premature skin aging. Previous studies suggest that the activation of autophagy can protect oxidation-induced cellular damage and aging-like changes in skin. In order to develop new anti-pollution ingredients, this study screened various kinds of natural extracts to measure their autophagy activation efficacy in cultured dermal fibroblast. The stimulation of autophagy flux by the selected extracts was further confirmed both by the expression of proteins associated with the autophagy signals and by electron microscope. Crepidiastrum denticulatum (CD) extract treated cells showed the highest autophagic vacuole formation in the non-cytotoxic range. The phosphorylation of adenosine monophosphate kinase (AMPK), but not the inhibition of mammalian target of rapamycin (mTOR), was observed by CD-extract treatment. Its anti-pollution effects were further evaluated with model compounds, benzo[a]pyrene (BaP) and cadmium chloride (CdCl₂), and a CD extract treatment resulted in both the protection of cytotoxicity and a reduction of proinflammatory cytokines. These results suggest that the autophagy activators can be a new protection regimen for anti-pollution. Therefore, CD extract can be used for anti-inflammatory and anti-pollution cosmetic ingredients.

Several studies have suggested that adiponectin is an anti-aging molecule based on its potential involvement of adipose tissue in skin aging. In this study, we investigated the anti-photoaging efficacy of an adiponectin expression-stimulating peptide derivative, pentasodium tetracarboxymethyl hexanoyl dipeptide-12 (PTHD-12), in in vitro and ex vivo human skin explant models. A double-blind, randomized, comparator placebo-controlled study was performed to confirm clinical efficacy. After irradiation with 50 mJ/cm² of UVB, a UV-induced decrease in adiponectin expression and an increase in inflammatory cytokines in cultured human dermal fibroblasts were prevented by the PTHD-12 treatment test peptide. Mitigation of cellular senescence and senescence-associated secretory phenotype (SASP) expressions induced by UVB (50 mJ/cm²) exposure were also mitigated by the post-treatment of PTHD-12, which was also observed in an ex vivo human skin explant model. The restoration of filaggrin, loricrin, and claudin-1 protein expression in a cultured human skin explant was observed. A clinical study further confirmed that the restoration of UVB-induced skin damage, represented by increased skin redness and trans-epidermal water loss, was accelerated by the use of test peptide PTHD-12-containing products. These results suggest that targeting adiponectin may be a plausible strategy for the development of anti-aging ingredients.

Several studies have suggested that adiponectin is an anti-aging molecule based on its potential involvement of adipose tissue in skin aging. In this study, we investigated the anti-photoaging efficacies of an adiponectin expression-stimulating peptide derivative in in vitro and ex vivo human skin explant models. A double-blind, randomized, placebo-controlled study was performed to confirm the clinical efficacies. UV-induced decrease in adiponectin expression and increase in inflammatory cytokines were prevented by the test peptide. Mitigation of cellular senescence and senescence-associated secretory phenotype (SASP) expression has also been observed in ex vivo human skin. Restoration of filaggrin, loricrin, and claudin-1 protein expression was observed. A clinical study further confirmed that the restoration of UVB-induced skin damage, represented by increased skin redness and trans-epidermal water loss, was accelerated by the use of test peptide-containing products. These results suggest that targeting adiponectin may be a plausible strategy for the development of anti-aging ingredients.

Peptides are recognized as multifunctional bioactive ingredients in cosmetic science, as they offer diverse beneficial effects such as skin rejuvenation, anti-aging, and skin barrier enhancement. In this study, we applied a cheminformatics-assisted peptidomimetic design platform to design novel peptides targeting heat shock protein 47 (Hsp47), a collagen-specific molecular chaperone that is downregulated during skin aging. Using molecular fingerprint similarity-based peptide design and protein–peptide docking simulations, five candidate peptides were screened, among which ICP-1225 (TY) emerged as a potent stimulator of Hsp47 and collagen (COL1A1 and COL3A1) expression in dermal fibroblasts. To improve stability and skin penetration, fatty acid-conjugated derivatives of ICP-1225 were synthesized, and acetyl-TY (ICP-1236) demonstrated the most consistent upregulation of Hsp47 and collagen in vitro. Restoration of Hsp47 protein expression and dermal collagen levels in UVB-damaged ex vivo human skin explants was also observed. These findings highlight the potential of cheminformatics-assisted peptide design in the development of next-generation cosmetic actives. ICP-1236 represents a promising anti-wrinkle candidate through the modulation of Hsp47 and collagen pathways, warranting further clinical evaluation.