In vitro hair growth-promoting effect of Lgr5-binding octapeptide in human primary hair cells.

BACKGROUND: Hair loss occurs due to various biological and environmental causes, which can have psychosocial consequences. The Wnt/ß-catenin signaling is well-known for its role in hair growth and regeneration, as it induces the proliferation and differentiation of hair cells. When the leucine-rich G protein-coupled receptor 5 (Lgr5) interacts with the R-spondins, the frizzled receptor (FZD), a Wnt receptor, becomes stabilized, resulting in an increased ß-catenin activity. AIM: We investigated whether the octapeptide that binds to Lgr5 enhances proliferation and differentiation of human primary hair cells through the activation of Wnt/ß-catenin signaling. METHODS: The binding affinity of the octapeptide to Lgr5 was evaluated using surface plasmon resonance (SPR). We confirmed changes in proliferation and related factors like ß-catenin activation and growth factors (GFs) expression in human hair follicle dermal papilla cells (HHFDPCs). Additionally, we observed the proliferation and the expression of differentiation markers in human hair follicle outer root sheath cells (HHFORSCs), human hair follicle germinal matrix cells (HHFGMCs), and human hair follicle stem cells (HHFSCs). We used three-dimensional HHFDPC spheroid culture treated with dihydrotestosterone (DHT) to create in vitro conditions that mimic androgenetic alopecia, and we studied the effects of octapeptide on Wnt expression and HHFSC differentiation. RESULTS: The binding of the octapeptide to Lgr5 was confirmed using SPR analysis. In HHFDPCs, treatment with octapeptide resulted in a concentration-dependent increase in proliferation. We also observed increased nuclear translocation of ß-catenin and increased expression of its downstream targets. HHFDPCs treated with octapeptide exhibited increased expression of growth factors and phosphorylation of Akt and ERK. In addition, we confirmed that octapeptide increased proliferation and induced differentiation in HHFORSCs, HHFGMCs, and HHFSCs. Under the HHFDPC spheroid culture conditions, we found that octapeptide restored the inhibition of Wnt-5a and Wnt-10b expressions by DHT. In HHFSCs treated with HHFDPC spheroid culture media, we observed that octapeptide recovered the inhibition of differentiation by DHT. CONCLUSION: We found that octapeptides activated the Wnt/ß-catenin signaling and induced the proliferation and differentiation of human primary hair cells by acting as an exogenous ligand for Lgr5. In addition, octapeptides recovered inhibited hair regeneration characters by DHT in androgenetic alopecia-mimic in vitro model. These findings suggest that octapeptides may be a promising therapeutic option for treating hair loss.

Lowering of Blood Glucose Levels with the Peptide Mixture Deglusterol in In Vitro and In Vivo Models.

This study aimed to investigate the blood glucose-lowering effect of the peptide complex Deglusterol, which was isolated from corn extract, in insulin-resistance models. It was found to inhibit insulin receptor substrate (IRS) Ser302 phosphorylation, known as the insulin resistance mechanism, through the inhibition of tumor necrosis factor-α (TNF-α) signaling and the induction of AMP-activated protein kinase phosphorylation. Furthermore, the phosphorylation of IRS Tyr632, phosphoinositide 3-kinase (PI3K), and AKT that is involved in the insulin action mechanism was decreased by TNF-α, whereas Deglusterol increased their phosphorylations, leading to an increase of glucose uptake rate by 190% through glucose transporter type 4 (GLUT4) compared with TNF-α-treated group in C2C12 cells. In addition to insulin signaling activation, Deglusterol treatment resulted in significantly greater mRNA expressions of IRS (190%) and GLUT4 (140%) as well as that of leptin (260%) and adiponectin (140%), which are indicators of insulin sensitivity. In animal models with type 2 diabetes, the blood glucose concentrations in the Deglusterol-administered group were significantly reduced by 50% compared with the control group. Deglusterol suppressed insulin resistance and restored insulin sensitivity, which contributed to lowering blood glucose concentrations in the insulin-resistant models, suggesting its potential as a blood glucose-lowering agent for people at high risk of type 2 diabetes or prediabetes.

Whitening effect of novel peptide mixture by regulating melanosome biogenesis, transfer and degradation.

Peptides are short chain of amino acids linked by peptide bonds. They are widely used as effective and biocompatible active ingredients in cosmetic industry. In this study, we developed novel peptide mixture and identified its anti-pigmentation effect on melanocytes and keratinocytes. Our results revealed that peptide mixture inhibited melanosome biogenesis through the regulation of microphthalmia-associated transcription factor, a key factor of melanogenesis in melanocytes. And we observed that peptide mixture inhibited melanosome uptake through the reduction of protease-activated receptor 2, a phagocytosis-related receptor in keratinocytes. Furthermore, peptide mixture activated autophagy system resulting in degradation of transferred melanosomes in keratinocytes. The anti-pigmentation effect of multi-targeting peptide mixture was assessed in a human skin equivalent model (MelanoDerm). Melanin contents in epidermal layer were significantly decreased by topical treatment of peptide mixture, suggesting that it can be applied as a novel cosmetics material having a whitening function.