Palmitoylethanolamide (PEA) exhibits multiple skincare functions such as anti-nociceptive and anti-inflammatory effects. However, its topical application is limited due to its difficulty in bypassing the stratum corneum barrier, relatively low bioavailability, and low stability. Herein, elastic nano-liposomes (ENLs) with excellent deformability and elasticity were utilized as a novel drug delivery system to encapsulate PEA to overcome the abovementioned issues and enhance the biological effects on the skin. ENL was prepared with phosphatidylcholine, cholesterol, and cetyl-PG hydroxyethyl palmitamide with a molar ratio mimicking skin epidermal lipids, and PEA was loaded. The PEA-loaded ENL (PEA-ENL) demonstrated efficient transdermal delivery and enhanced skin retention, with negligible cytotoxicity toward HaCaT cells and no allergic reaction in the human skin patch test. Notably, PEA-ENL treatment increased cell migration and induced significant regulation in the expression of genes associated with anti-nociceptive, anti-inflammatory, and skin barrier repair. The mechanism of the anti-nociceptive and anti-inflammatory effects of PEA was further investigated and explained by molecular docking site analysis. This novel PEA-ENL, with efficient transdermal delivery efficiency and multiple skincare functionalities, is promising for topical application.

Quercetin and carnosine, natural antioxidants with anti-aging and photoprotective potential, face therapeutic limitations due to poor skin permeability. We engineered EV-QuerCar, a liposomal-based nanoparticles (LPNs) system co-encapsulating both compounds, to enhance transdermal delivery and evaluate its structural and functional efficacy. EV-QuerCar was prepared biomimetically using thermophilic bacterial lipids via ultracentrifugation, thin-film hydration, and high-pressure homogenization. Physicochemical properties, transdermal penetration, cellular uptake, and cytotoxicity were tested in vitro. Molecular docking and qPCR assessed pathway targeting. EV-QuerCar exhibited uniform size (94.70 ± 0.71 nm), high encapsulation efficiency (90.07%), sustained release, and 3.21-fold enhanced transdermal absorption compared to free compounds. Cellular uptake in fibroblasts increased time-dependently (up to 5.48-fold at 4 h). Molecular docking and qPCR confirmed interactions with NRF2 and HES1 targets, significantly upregulating their mRNA levels (2.29- and 3.35-fold, respectively) in UV-exposed human fibroblasts. EV-QuerCar improves skin permeability and antioxidant efficacy, highlighting its cosmeceutical promise.

As a traditional hair-growth-promoting herb, Platycladi Cacumen (PC) has a long history of folk application in the field of hair loss improvement. Preliminary modern pharmacological studies have suggested that its active components may exert potential effects by regulating hair follicle-related signaling pathways; however, for androgenetic alopecia (AGA), the exact targets and specific regulatory mechanisms of PC remain unelucidated, which provides a direction for research on natural drug-based intervention in AGA. In this study, network pharmacology was employed to predict the active components and core targets of PC. Targets associated with AGA were collected, and the intersection targets between PC and AGA were identified. Subsequently, protein-protein interaction (PPI) analysis, Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the intersection targets to screen out the core targets. Thereafter, molecular docking and molecular dynamics(MD) simulation were conducted to validate the interactions between key active components and core targets. The component-target network diagram included 1044 interaction relationships between 32 components and 439 targets, among which quercetin(160), apigenin(150), myricetin(129), and hinokinin(105) were identified as key components. The disease-target network diagram summarized 410 targets associated with AGA. Through PPI network analysis, key targets such as ESR1(46), BCL2(44), INS(44), AR(42), and STAT3(40) were screened out. The results of GO enrichment analysis and KEGG pathway analysis revealed that PC may exert its effects by regulating the EGFR receptor molecule and pathways including the HIF-1 signaling pathway. Molecular docking results showed that the binding energies of all complexes were less than -5.0 kcal/mol, indicating favorable binding effects. MD simulation results showed that the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), two-dimensional free energy landscape (FEL-2D), and FEL-3D of the simulation system all remained in an equilibrium state with small fluctuation amplitudes. This result indicated that the molecular system had a stable overall conformation, restricted local residue movement, a compact spatial structure, and stable internal chemical bonds–collectively predicting that the quercetin-STAT3, apigenin-AR, myricetin-STAT3, and hinokinin-AR complexes may exhibit satisfactory binding stability. Collectively, Overall, this study systematically investigated the mechanism of action and potential value of PC leaves in intervening in AGA, providing a solid theoretical basis for the intervention of AGA with PC.

Introduction: Dermal papilla cells regulate hair follicle growth, yet bioactive peptides that influence both pro-growth signaling and androgen receptor (AR)-associated regulation remain poorly characterized. This study evaluated the effects of Myristoyl Tetrapeptide-12 (MT12) on human dermal papilla cell function and its potential interaction with the AR ligand-binding domain (AR-LBD). Methods: Human dermal papilla cells were treated with MT12, with bicalutamide as a pharmacological reference. Cell viability, proliferation, and expression of Wnt/ β -catenin-related, AR-associated, and hair-growth-related genes were assessed by CCK-8, EdU incorporation, and quantitative PCR, respectively. Molecular docking, 500-ns molecular dynamics simulations, and residue communication-network analysis were used to characterize MT12–AR-LBD interactions. Results: MT12 showed good cytocompatibility and significantly increased dermal papilla cell proliferation, with EdU-positive cells increasing from approximately 5% in controls to 18%–22% after treatment. MT12 increased CTNNB1 and WNT5A expression and reduced DKK1 expression, together with changes in AR , TGF- β 1 , and PEDF/SERPINF1 transcripts. Computational analyses indicated that MT12 remained associated with the AR-LBD binding pocket and altered local flexibility, conformational sampling, correlated residue motions, and intradomain communication. A recurrent ASN705–MET895–ILE898 route linked the ligand-binding region to the H12/AF-2 regulatory region. Discussion: MT12 promotes dermal papilla cell proliferation and induces a Wnt/ β -catenin-related transcriptional profile consistent with pro-growth signaling, while structural analyses suggest modulation of AR conformational dynamics. These integrated cellular and computational findings support MT12 as a potential modulator of dermal papilla cell function, although AR-related activity and the causal role of Wnt/ β -catenin signaling require further validation.

As a traditional hair-growth-promoting herb, Platycladi Cacumen(PC) has a long history of folk application in the field of hair loss improvement. Preliminary modern pharmacological studies have suggested that its active components may exert potential effects by regulating hair follicle-related signaling pathways; however, for androgenetic alopecia (AGA), the exact targets and specific regulatory mechanisms of PC remain unelucidated, which provides a direction for research on natural drug-based intervention in AGA. In this study, network pharmacology was employed to predict the active components and core targets of PC. Targets associated with AGA were collected, and the intersection targets between PC and AGA were identified. Subsequently, protein-protein interaction (PPI) analysis, Gene Ontology (GO) enrichment analysis, and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed on the intersection targets to screen out the core targets. Thereafter, molecular docking and molecular dynamics simulation were conducted to validate the interactions between key active components and core targets. The component-target network diagram included 1044 interaction relationships between 32 components and 439 targets, among which quercetin, apigenin, myricetin, and hinokinin were identified as key components. The disease-target network diagram summarized 410 targets associated with AGA. Through PPI network analysis, key targets such as ESR1, BCL2, INS, AR, and STAT3 were screened out. The results of GO enrichment analysis and KEGG pathway analysis revealed that PC may exert its effects by regulating the EGFR receptor molecule and pathways including the HIF-1 signaling pathway. Molecular docking results showed that the binding energies of all complexes were less than -6.4 kcal/mol, indicating favorable binding effects. Molecular dynamics simulation results showed that the root-mean-square deviation (RMSD), root-mean-square fluctuation (RMSF), radius of gyration (Rg), solvent-accessible surface area (SASA), two-dimensional free energy landscape (FEL-2D), and FEL-3D of the simulation system all remained in an equilibrium state with small fluctuation amplitudes. This result indicated that the molecular system had a stable overall conformation, restricted local residue movement, a compact spatial structure, and stable internal chemical bonds—collectively confirming that the quercetin-STAT3, apigenin-AR, myricetin-STAT3, and hinokinin-AR complexes exhibited extremely strong binding stability. Collectively, Overall, this study systematically investigated the mechanism of action and potential value of PC leaves in intervening in AGA, providing a solid theoretical basis for the intervention of AGA with PC.