Discovery of Zeylenone from Piper griffithii (Piperaceae) as a Potential Anti-Acne Bacterial Agent and Its Mechanism of Action Against Acne-Causing Bacteria

An abnormal increase in acne-causing bacteria is the main cause of acne. This study aimed to investigate Piper griffithii C.DC. as a new source of compounds for inhibiting acne-causing bacteria and to provide the first elucidation of the mechanism of action against these bacteria. The antibacterial efficacy of 27 Piper species was examined against acne-causing clindamycin-resistant bacterial strains. Antibacterial activity of various crude extracts derived from leaves or stems extracted using hexane, ethyl acetate, or ethanol was evaluated. Ethyl acetate leaf extract of P. griffithii exhibited the greatest antibacterial effect against all tested bacteria. Zeylenone, an antibacterial substance isolated, purified, and characterized from the ethyl acetate leaf extract of P. griffithii, disrupts cell walls and membranes. Minimum bactericidal concentration (MBC) values were 1.25, 2.5, and 7.5 mg/mL for Cutibacterium acnes, Staphylococcus aureus, and S. epidermidis, respectively. Zeylenone derived from P. griffithii leaves was nontoxic to human skin keratinocytes (HaCaT). A formulated anti-acne gel with zeylenone was effective in controlling acne-causing bacteria. These results suggest that zeylenone isolated from P. griffithii leaves can be further developed as a natural ingredient in anti-acne products. This is the first report of the use of zeylenone from P. griffithii for eliminating acne-causing bacteria.