Skin aging is a complex process involving both intrinsic and extrinsic factors, with ultraviolet (UV) radiation being a primary contributor to extrinsic aging, also known as photoaging. UV exposure leads to a cascade of damaging effects on the skin, including decreased adiponectin expression and increased inflammatory cytokines, ultimately contributing to cellular senescence, degradation of the skin barrier, and visible signs of aging. Adiponectin, an adipokine with reported anti-aging properties, has been shown to be reduced in UV-exposed skin, and its experimental depletion exacerbates photoaging-like symptoms. Therefore, strategies aimed at stimulating adiponectin expression in the skin were considered a plausible approach to mitigate UV-induced skin damage and combat photoaging. This study investigates the in vitro, ex vivo, and clinical efficacy of a novel adiponectin expression-stimulating peptide derivative, pentasodium tetracarboxymethyl hexanoyl dipeptide-12 (PTHD-12), with a particular focus on its topical application in addressing UV-induced skin damage.
Methods
The study utilized an ex vivo human skin explant model where skin tissues were exposed to UVB radiation, followed by the topical application of either a test sample solution containing PTHD-12 or a blank solution once a day for two days. Immunohistochemical staining was then performed to assess changes in adiponectin and inflammatory markers. Furthermore, a double-blind, randomized, placebo comparator-controlled clinical study involved 20 healthy female volunteers who received UVB irradiation on their dorsal areas. Following irradiation, participants topically applied either a test product containing PTHD-12 (100 ppm) or a placebo comparator product twice daily for seven days. Trans-epidermal water loss (TEWL) and skin redness were measured at baseline, immediately after irradiation, and at 3 and 7 days after irradiation to evaluate the recovery from UV-induced damage.
Key Findings
•In the ex vivo model, topical application of PTHD-12 significantly upregulated adiponectin expression in both the basal and spinous layers of UVB-exposed skin.
•Topical PTHD-12 application in the ex vivo model prevented the UVB-induced increase in the expression of p16INK4a, a marker of senescent cells.
•The epidermal expression of tumor necrosis factor-α (TNF-α), increased by UVB exposure in the ex vivo model, was decreased by the topical application of PTHD-12.
•Topical application of the adiponectin-stimulating peptide in the ex vivo model restored the expression of skin barrier proteins filaggrin, loricrin, and claudin-1, which were reduced by UVB exposure.
•The clinical study demonstrated that the topical application of the PTHD-12-containing product significantly accelerated the recovery rate of both skin redness and trans-epidermal water loss (TEWL) in UVB-irradiated skin compared to the placebo.
•The test group treated with the PTHD-12 product showed the highest recovery rate for skin redness and TEWL compared to the placebo and non-treated groups.
This study demonstrates the novel clinical efficacy of topically applied adiponectin-stimulating peptide PTHD-12 in accelerating the recovery from UVB-induced skin damage, as evidenced by the faster restoration of skin redness and skin barrier function. The novelty of this research lies in being the first report on the clinical effects of an adiponectin-stimulating peptide for cosmetic applications, highlighting its potential to mitigate photoaging by upregulating adiponectin expression, reducing inflammatory markers and cellular senescence, restoring skin barrier proteins, and accelerating the recovery of UV-induced skin irritation and barrier disruption. Future implications of this research include further long-term clinical studies with a larger number of participants to confirm the broader anti-aging effects of topical PTHD-12. Additionally, further investigation into the specific mechanisms and optimal formulations for topical delivery of adiponectin-stimulating peptides is warranted.
Link to the study: https://www.mdpi.com/2079-9284/12/2/54
