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.

Among the complex and diverse triggering and aggravating factors for sensitive skin syndrome, potential defects in skin barrier function are considered one of the most important ones. Previously, we have reported improvements in skin barrier function thanks to autophagy-activating peptide derivatives. Further investigation revealed that the activation of autophagy signaling in skin cells also attenuated inflammatory responses induced by UV irradiation or exposure to pollution. In this study, in vitro and ex vivo human skin explant models were used to evaluate the potential benefits of the autophagy-activating peptide, pentasodium tetracarboxymethyl palmitoyl didpeptide-12 (PTPD-12), on sensitive skin-related parameters. Clinical efficacy testing was also performed to confirm the skin barrier-improving and skin-soothing activities of the autophagy-activating peptide. As a result, significant reductions in inflammatory cytokine (IL-8 and TNF-α) and enzyme activity (PDE4) were observed in the in vitro system. Increased expression of barrier marker proteins by PTPD-12 in UV-irradiated human skin tissue was observed ex vivo. In a clinical study, delayed response to topical capsaicin-induced vascular activation, which represents enhanced epidermal permeability barrier function, was observed after 4 weeks of application of PTPD-12 in healthy volunteers. In another clinical study with sensitive skin carriers identified via a lactic acid stinging test, a significant reduction in trans-epidermal water loss (TEWL) and skin erythema index was observed after 4 weeks of PTPD-12 usage. These results suggest that the activation of autophagy can be a potential treatment regimen for sensitive skin syndrome, specifically in terms of skin barrier function enhancement and skin soothing.

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.

Despite the potential benefits of cannabidiol as a skin-soothing ingredient, its regulatory status hampers its general use in cosmetic products in many countries. To develop an alternative to cannabidiol, fatty acid amide molecules mimicking the chemical structure of endocannabinoids were manufactured using a lipase-catalyzed process. A mixture of fatty acid amides from sunflower oil and 1-amino propan-3-ol was synthesized using an immobilized lipase reaction, and the activation of cannabinoid receptor 1 (CB1R) was measured using a cAMP assay. The anti-inflammatory activity of the endocannabimimetic ingredients was evaluated in cultured human monocytes and ex vivo human skin explant models. A clinical study was conducted to address the skin hydration, skin barrier function, and skin redness, and the ratio of the interleukin-1-receptor antagonist (IL1-RA) to IL-1α in corneocytes, as a marker for skin sensitivity, were also measured. As a result, the activation of CB1R by endocannabimimetic ingredients was observed in cAMP assays, and a reduction in inflammatory responses by human monocytes induced by lipopolysaccharide treatment were also observed. External stress-induced inflammatory responses were reduced in ex vivo human skin explants. Improvements in skin hydration and barrier function were observed in a clinical study. A significant decrease in skin redness and the IL-1RA to IL-1α ratio was also observed. Endocannabimimetic ingredients, as alternatives to cannabidiol, can be used in skin-soothing cosmetics to increase skin hydration, improve skin barrier function, and reduce skin sensitivity.

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.