Abstract
OBJECTIVE: Although bioactive compounds from single herbs are extensively explored in cosmetics, the synergistic potential of herbal combinations remains understudied. This study aimed to evaluate the stability of a combined extract of Panax ginseng, Ganoderma lucidum, Cordyceps militaris, and several Asian plants (PGC), and its multifunctional efficacy for acne-related skin dysfunction. METHODS: PGC was analyzed using high-performance liquid chromatography (HPLC) for batch consistency and bioactive quantification. Network pharmacology and molecular docking were used to identify active components and targets and assess binding affinities, respectively. In vitro assays were conducted to evaluate antibacterial activity, skin barrier repair, keratinocyte migration, reactive oxygen species (ROS) reduction, anti-inflammatory effects, and inhibition of lipid accumulation. The safety was tested via cytotoxicity assessments. RESULTS: HPLC analysis validated batch consistency and identified key bioactive constituents in PGC, including phenolic acids, flavonoids, and alkaloids. Integrated network pharmacology and molecular docking revealed multitarget mechanisms through the regulation of the IL-17/TNF/NF-κB axis pathway modulation. PGC exhibited potent antibacterial efficacy against acne-associated pathogens (Cutibacterium acne, MIC = 25 μg/mL), restored skin barrier integrity (filaggrin, +235%; loricrin, +261%), and sodium dodecyl sulfate (SDS)-induced damage (85%). Concurrently, PGC accelerated keratinocyte migration (40%), reduced ROS (45%) and abnormal lipid droplet content (60%), and attenuated inflammatory responses (40% nitric oxide (NO) inhibition) while maintaining biosafety (no cytotoxicity ≤ 200 μg/mL). CONCLUSION: PGC exemplified the translational potential of herbal compatibility, offering a multitargets solution for acne management through integrating antibacterial, barrier-repair, anti-inflammatory actions, and several other effects. This study established a network pharmacology-guided framework for developing evidence-based multitargets cosmetics.