Lignan-rich Norway spruce (Picea abies) resin extract exhibits anti-inflammatory, skin-regenerative and anti-acne effects: In vitro, in silico, biocompatibility and exploratory clinical findings.

OBJECTIVE: To investigate the antimicrobial, anti-inflammatory and early pro-repair properties of Picea abies resin extract and a 30% extract-based cream and to explore preliminary in-use performance, tolerability and cosmetic acceptability in adults with mild acne. METHODS: The chemical composition of the extract was characterized by GC-MS. Anti-Cutibacterium acnes activity was evaluated by minimum inhibitory concentration (MIC) determination, time-kill testing and an inoculated-cream model. Anti-inflammatory and pro-repair effects were assessed in LPS-stimulated human keratinocytes by measuring IL-1α, IL-6 and IL-8, and in normal human dermal fibroblasts by cellular protein synthesis. Mechanistic plausibility was explored by Glide SP docking against AlphaFold2-generated models of IKKβ, JNK1, NF-κB and PPARγ. Safety was evaluated by ISO 10993-5 agar diffusion and a 48-h human patch test, and clinical performance was explored in a 28-day, open-label, uncontrolled in-use evaluation involving adults with mild facial acne. RESULTS: GC-MS identified p-coumaric acid, resin acids and the lignans pinoresinol, isolariciresinol and secoisolariciresinol as major constituents. The extract showed an MIC of 30% against C. acnes and, at this concentration, achieved a > 4.9-log10 reduction after 8 h, whereas the cream containing 30% extract achieved a 4.03-log10 reduction after 8 h in the inoculated-cream model. In LPS-stimulated keratinocytes, the cream reduced IL-1α by 14-17%, IL-6 by 22-39% and IL-8 by 16-26%. In dermal fibroblasts, cellular protein synthesis increased by 35-50% within 24-48 h. Docking identified putative interactions of lignans and p-coumaric acid with IKKβ, JNK1, NF-κB and PPARγ, providing hypotheses for further mechanistic investigation. No cytotoxicity or irritation was observed. In an exploratory open-label 28-day in-use study (n = 31), total lesions decreased 26.8% (p < 0.0001), papules 52.1% (p = 0.001) and comedones 17.6% (p < 0.0001), with 87% favourable acceptability and no reported intolerance. CONCLUSION: Picea abies resin extract and the extract-containing cream demonstrated antimicrobial, anti-inflammatory and early pro-repair activities in preclinical models, with good tolerability. Docking identified potential compound-target interactions that may help guide future mechanistic studies. The exploratory 28-day in-use evaluation provided preliminary signals of reduced papules and comedones/microcysts and good cosmetic acceptability. These findings support further mechanistic investigation in adequately powered, randomized, vehicle-controlled clinical studies.