The dermo-cosmetics industry relies heavily on bioactive ingredients like synthetic peptides for their purported skin benefits, including anti-aging and wound healing. However, a significant issue within this field is the lack of comprehensive genetic validation for the mechanisms of action of many cosmetic peptides, despite their widespread use. E-cadherin, a glycoprotein crucial for cell adhesion and implicated in tissue repair, has remained relatively underexplored concerning how these peptides might exert their effects at the molecular level. The synthetic acetyl hexapeptide-1 (Ac-ARHLFW-NH2) is known for its potential wound healing and anti-aging properties and has been incorporated into cosmetic formulations. This research considered acetyl hexapeptide-1 as a potential solution to the need for genetically validated cosmetic peptides by specifically investigating its impact on the expression of the CDH-1 gene, which encodes E-cadherin. The study aimed to elucidate the molecular basis of this peptide’s claimed benefits by examining its effect on a key gene involved in cellular adhesion and tissue regeneration.
The study involved the in-house synthesis of acetyl hexapeptide-1 using microwave-assisted solid-phase peptide synthesis. Human hepatocytes HepG2 cells were then exposed to the synthesized peptide to evaluate cytotoxicity and its effect on gene expression. Quantitative PCR (qPCR) was employed to analyze the expression levels of the CDH-1 gene and apoptosis-related genes. Statistical analysis was performed to determine the significance of the observed changes in gene expression.
Section-wise Key Findings
•Characterization of Ac-ARHLFW-NH2 Hexapeptide: The synthesized peptide exhibited high purity (92%) and demonstrated the ability to self-assemble into nanoscale structures in an aqueous solution. This self-assembly is likely due to its amphiphilic nature, potentially enhancing skin penetration and stability.
•Cell Growth Kinetics of HepG2 Cells: Treatment of HepG2 cells with 0.6 mg/mL of the acetyl hexapeptide-1 showed no significant cytotoxic effects over a 96-hour period. Cell growth and death rates were similar between treated and untreated cells, indicating the biocompatibility of the peptide at the tested concentration. Furthermore, there were no significant changes in the expression of apoptosis-related genes (BAX, Bcl-2, Caspase-9) and the cell cycle-related gene Cyclin D1 after 72 hours of treatment, further confirming the absence of cytotoxicity.
•Analysis of the Effect of the Ac-ARHLFW-NH2 Hexapeptide on Gene Expression: The most significant finding was a statistically significant increase in the expression of the CDH-1 gene (encoding E-cadherin) in HepG2 cells treated with the acetyl hexapeptide-1 at 24 hours, with the effect peaking at 48 hours. This upregulation suggests that the peptide can positively influence cellular adhesion and potentially promote tissue repair. While CDH-1 expression decreased after 48 hours, the treated cells still maintained higher expression levels compared to the control group.
This research offers a novel contribution by providing genetic validation for the molecular effects of acetyl hexapeptide-1, specifically demonstrating its ability to significantly upregulate the expression of the CDH-1 gene without inducing cytotoxicity. This finding highlights the potential of this peptide for tissue rejuvenation and wound healing applications in cosmeceutical formulations by enhancing cell-cell adhesion and contributing to epithelial integrity. The study underscores the need for future research to explore the peptide’s stability, efficacy in various formulations, and effects on skin-relevant cell models to fully realize its potential in skincare and other biomedical applications.
Link to the study: https://www.mdpi.com/2079-9284/12/2/48
