In silico, in vitro and topical formulation of apigenin from Apium graveolens L. as a natural anti-hyperpigmentation agent

¹ Division of Pharmacy, School of Veterinary Medicine and Biomedical Sciences, IPB University, Bogor, 16680, Indonesia
² Division of Biochemistry, Faculty of Mathematics and Natural Science, IPB University, Bogor, 16680, Indonesia

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Abstract

Apigenin from Apium graveolens L. was evaluated as a natural anti-hyperpigmentation agent using integrated in silico, in vitro, and topical formulation approaches. Molecular docking against melanogenesis related enzymes showed favorable binding energies toward tyrosinase (−7.5 kcal/mol), tyrosinase related protein 1 (TYRP1) (−7.9 kcal/mol), and dopachrome tautomerase (−7.2 kcal/mol). Antioxidant activity assessed by the thiobarbituric acid (TBA) assay demonstrated concentration-dependent inhibition of lipid peroxidation, reaching a maximum inhibition of 65.1% at 25 ppm (p < 0.05), followed by reduced activity at higher concentrations. Tyrosinase inhibitory assays revealed mild but significant concentration-dependent inhibition (11.1−38.2%) between 3,125 and 50,000 ppm. Apigenin was formulated into a carbomer 934 gel, exhibiting suitable viscosity and stable rheological properties over four weeks. These findings indicate that apigenin acts primarily as an antioxidant with supplementary tyrosinase modulation, supporting its potential use in stable topical anti-hyperpigmentation formulations.