Tanshinone in acne therapeutics: Integrating molecular mechanisms, drug development, and multimodal treatment strategies

Tanshinones (TS), bioactive lipophilic diterpenoids derived from Salvia miltiorrhiza(SM), demonstrate significant therapeutic promise for acne vulgaris (AV)—a multifactorial dermatosis characterized by P.acnes colonization, aberrant follicular keratinization, and immune-inflammatory cascades exacerbated by endocrine dysregulation and psychosocial stressors. This comprehensive review synthesizes recent advances elucidating TS's tripartite mechanistic framework: (1) Direct antibacterial activity against P. acnes and multidrug-resistant Staphylococcus aureus, disrupting biofilm formation and quorum sensing; (2) Immunomodulation via suppression of NLRP3 inflammasomes, inhibition of MAPK/NF-κB signaling pathways, and downregulation of pro-inflammatory cytokines; (3) Sebostatic and antioxidant effects through modulation of SREBP-1/FASN-mediated lipid biosynthesis, Nrf2/ARE pathway activation, SOD/COX-2 regulation, and potent ROS scavenging. Innovations in pharmaceutical engineering—including carrier-free self-assembled nanoparticles, autolytic microneedle arrays, photoactivated nanoemulsions, and chitosan-based nanoencapsulated gels—have markedly enhanced TS bioavailability, dermal retention, and pilosebaceous targeting. Clinical evaluations confirm TS formulations significantly reduce inflammatory lesion counts, acne recurrence rates, serum testosterone, and oxidative stress biomarkers. Synergistic regimens combining TS with photodynamic therapy, intense pulsed light, or conventional agents demonstrate enhanced anti-acne efficacy while minimizing cutaneous irritation. Despite promising outcomes, translational challenges persist, including pharmacokinetic limitations, clinical validation gaps in long-term safety, and scale-up complexities of advanced delivery systems. Future research should prioritize randomized multicenter trials, predictive ex vivo models, and hybrid delivery platforms to accelerate evidence-based integration into dermatological practice.