Integrative Assessment of Glycyrrhiza uralensis Extract in Cosmetics Using HPLC Analysis, Network Pharmacology, and Computational Threshold of Toxicological Concern-Based Safety Evaluation

Licorice <i>(Glycyrrhiza uralensis)</i> contains bioactive flavonoids and saponins, primarily liquiritin and glycyrrhizin, which exhibit pharmacological activities but also potential dose-dependent toxicity. This study aimed to establish an integrative workflow combining analytical chemistry, network pharmacology, and computational toxicology to evaluate the skin-related safety of these compounds. High-performance liquid chromatography (HPLC) was employed to quantify liquiritin and glycyrrhizin in licorice extract. Network pharmacology and molecular docking analyses were conducted to identify core toxicity-related targets. In silico toxicity and threshold of toxicological concern (TTC) assessments were performed using VEGA and database-driven prediction models to estimate dermal exposure risk. Liquiritin and glycyrrhizin were identified as major constituents of <i>G. uralensis</i>. Network analysis revealed three key targets-EGFR, STAT3, and SRC-linked to skin sensitivity and toxicological pathways, including TRP channel regulation and EGFR signaling. Molecular docking showed strong binding affinities to SRC. The threshold of toxicological concern evaluation indicated that liquiritin exposure remained below safety thresholds, while glycyrrhizin slightly exceeded but remained within acceptable limits. The proposed HPLC-network pharmacology-TTC workflow provides a novel, non-animal approach for early-stage cosmetic safety screening. Both compounds demonstrate acceptable safety margins, supporting their controlled use in dermal formulations.