In Silico Study of Naringenin as Melanogenesis Inducer in Vitiligo

Abstract

Introduction: Vitiligo is a pigmentation disorder characterized by loss of skin color (depigmentation) due to melanocyte dysfunction and loss. Melanocytes produce melanin pigment through a melanogenesis process. Melanocyte survival and melanogenesis process are influenced by Microphthalmia Associated- Transcription Factor (MITF) and several proteins, including WNT, β-catenin, tyrosinase, Tyrosinase- Related Protein-1 (TRP1), and Tyrosinase-Related Protein-2 (TRP2). The current therapy for vitiligo is still unsatisfactory. Naringenin is one of Rhizophora mucronata compound, one type of mangrove plant often found in the eastern coastal area of Surabaya City. Objective: To investigate the naringenin’s potency in melanogenesis and to predict the pharmacokinetics or toxicity of naringenin by in silico study. Methods: This is a computational study using a molecular docking method to observe the interaction of naringenin with WNT, β-catenin, MITF, tyrosinase, TRP-1, and TRP-2 proteins. Pharmacokinetic or toxicity prediction of naringenin using the pkCSM method. Psoralen was used as a control. Results: Naringenin binds to all these proteins in the same region as psoralen, indicating that naringenin can stimulate melanogenesis. Naringenin has lower binding energy than psoralen on all proteins (except β-catenin), indicating that naringenin's interaction with these proteins is stronger than psoralen. Pharmacokinetic and toxicity predictions show that naringenin has good absorption or permeation, is not mutagenic, is not hepatotoxic, and does not cause skin sensitization. Conclusion: This computational study concludes that naringenin has melanogenesis inducer potency and good pharmacokinetics. Key words: Naringenin, Mangrove, Rhizophora mucronata, Vitiligo, WNT.