10.3390/polym8030084

Vollständiger Abstract

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<b>Background/Objectives:</b> Skin aging involves interconnected inflammatory, oxidative, hormonal, extracellular matrix (ECM), and cellular senescence-related mechanisms, supporting the need for multitarget approaches. This study aimed to evaluate the effects of a multicomponent natural product-based injectable formulation developed in Korean medicine practice, Dong-An Pharmacopuncture (DAP), on skin aging-related pathways. <b>Methods:</b> A network pharmacology approach was used to identify the active compounds, predicted molecular targets, and signaling pathways associated with DAP. Sixty-two active compounds from 11 constituent materials were screened, and 70 final targets were identified using STITCH-based prediction, intersection with GeneCards-derived skin aging-related targets, and quality filtering. <b>Results:</b> Herb-compound-target network analysis yielded 225 compound-target interactions across 292 edges. Protein-protein interaction analysis identified a highly connected network with 1,334 edges, and hub analysis converged on 10 core targets: <i>TNF</i>, <i>IL6</i>, <i>ESR1</i>, <i>TP53</i>, <i>AKT1</i>, <i>PPARG</i>, <i>EGFR</i>, <i>PTGS2</i>, <i>CASP3</i>, and <i>PPARA</i>. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses identified four major mechanistic axes: inflammatory and oxidative stress regulation, hormonal skin homeostasis, tissue repair and ECM remodeling, and cellular senescence-related regulation. Because DAP is administered by injection, a Good Laboratory Practice-compliant single-dose subcutaneous toxicity study was additionally conducted in Sprague-Dawley rats, which showed no mortality, abnormal clinical signs, or histopathological findings attributable to DAP at 1.0 mL/head. <b>Conclusions:</b> The findings in this study provide a systems-level framework for the predicted multitarget mechanisms of DAP in skin aging-related pathways and support the need for further experimental validation of its predicted mechanisms and repeated-dose safety.

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