Dihydromyricetin exerts dual anti-acne actions by suppressing propionibacterium acnes proliferation and host inflammatory responses via TLR2/NF-κB/MAPK pathway inhibition.

Acne is a common skin disorder, with Propionibacterium acnes (P. acnes) playing a central role in its pathogenesis. Despite the availability of various treatment options, current therapies are limited by safety concerns and reduced efficacy, highlighting the urgent need for the development of safer and more effective alternatives. This study demonstrated that dihydromyricetin (DMY), a natural flavonoid from Ampelopsis grossedentata, exhibited dual therapeutic actions against acne pathogenesis. DMY exerted potent bactericidal activity against P. acnes with a minimum inhibitory concentration of 0.5 mg/mL and minimum bactericidal concentration of 1 mg/mL, inducing bacterial membrane disruption. In P. acnes-stimulated human keratinocytes, DMY significantly reduced pro-inflammatory cytokine expression (IL-1β, TNF-α, IL-8) and suppressed Toll-like receptor 2 (TLR2) expression. Mechanistically, DMY inhibited phosphorylation of nuclear factor-kappa B (NF-κB) p65, c-Jun N-terminal kinase, and p38 mitogen-activated protein kinase (MAPK). In a murine acne model, topical application of 0.1 % DMY gel attenuated ear edema, decreased inflammatory cell infiltration (macrophages, neutrophils, CD4+ and CD8+ T cells), and reduced bacterial loads comparable to standard treatments (adapalene and clindamycin). Molecular docking revealed DMY binds TLR2 via hydrogen bonds with TYR-326 and LYS-347 residues. These findings establish DMY as a novel dual-functional agent against acne that simultaneously targets bacterial proliferation and host inflammatory pathways through TLR2/NF-κB/MAPK axis modulation.