In silico prioritization of Psidium guajava peel bioactives as putative multitarget modulators in acne vulgaris: An integrated evidence-mapping and network pharmacology review

Acne vulgaris is a common inflammatory skin disorder characterized by follicular hyperkeratinization, excessive sebum production, microbial dysbiosis, and persistent inflammation. Growing concerns regarding antibiotic resistance have increased interest in plant-derived therapeutics with multitarget activity. Psidium guajava peel is an underutilized agro-industrial byproduct rich in bioactive phytochemicals, particularly gallic acid and β-caryophyllene. An integrated evidence-mapping and network pharmacology approach was used to investigate the anti-acne potential of P. guajava peel bioactives. Literature screening followed a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA)-inspired workflow, and eligible studies were synthesized qualitatively. Network pharmacology analyses identified shared targets, protein–protein interaction networks, hub genes, and enriched pathways associated with acne vulgaris. Twenty-one studies met the inclusion criteria. Evidence indicated that gallic acid suppresses NF-κB and MAPK signalling while promoting tissue repair. β-Caryophyllene has been shown experimentally to bind CB2 and suppress NF-κB signalling; network analysis additionally predicts interactions with PI3 K/AKT/mTOR and STAT1/STAT3 pathways relevant to inflammation and sebaceous regulation that remain to be tested. Network pharmacology identified 85 nodes, 173 interactions, and nine shared predicted targets. Key hub genes included ESR1, ESR2, PPARG, MMP2, and EGFR that lay the groundwork for future experimental confirmation. Functional enrichment highlighted pathways regulating miRNA transcription, lipid storage, adipogenesis, and hormone-responsive signalling. These findings suggest that P. guajava peel exerts complementary multitarget effects against major acne pathogenic mechanisms and supports its potential valorization as a sustainable source of phytochemical-based anti-acne therapeutics. Further in vivo and clinical validation is required.