Antibacterial, Anti-Inflammatory and Anti-Melanogenic Effects of a Novel Peptide

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Background: Acne-induced post-inflammatory hyperpigmentation (PIH) is driven by Cutibacterium acnes-mediated inflammation and dysregulated melanogenesis; however, effective treatments targeting both processes remain limited.Objective: This study aimed to evaluate the anti-bacterial, anti-inflammatory, and anti-melanogenic effects of a newly made 2-isopropyl-5-methylphenol-conjugated valine-tryptophan dipeptide (2IP5MP-VW).Methods: IPMP-VW conjugates were synthesized and screened for antibacterial activity against C. acnes.The effects of 2IP5MP-VW on inflammation and melanogenesis were assessed using Raw 264.7 macrophages and Mel-ab cells, and ex-vivo human skin.Results: Among the synthesized candidates, 2IP5MP-VW showed the strongest antibacterial activity against C. acnes.2IP5MP-VW suppressed lipopolysaccharide-induced nitric oxide (NO) production via downregulation of inducible NO synthase without cytotoxicity.It also reduced melanin content in both unstimulated and forskolin-stimulated melanocytes.In ex vivo human skin, 2IP5MP-VW showed a decreasing trend in ultraviolet B-induced melanin accumulation.Conclusion: 2IP5MP-VW exhibits multifunctional anti-bacterial, anti-inflammatory, and anti-melanogenic activities, suggesting its potential as a candidate for the management of acne-induced PIH.