Isolation and development of rosmarinic acid derivatives from Zostera marina L. and evaluating their hypopigmentation activity: In vitro and in silico study

Abstract

Eelgrass, Zostera marina L., is vital to marine ecosystems, providing habitat, filtering pollutants, improving water quality, and serving as a source of bioactive compounds for pharmaceuticals. This study aimed to isolate and identify phenolic compounds from Z. marina, biotransform the main metabolite, rosmarinic acid (RA), and evaluate the anti-tyrosinase activity of these compounds. Various chromatographic techniques were employed to isolate compounds from Z. marina (1-4). Compound 1, exhibiting broad pharmaceutical activity, was biotransformed by Deinococcus geothermalis amylosucrase (DgAS) into two new glycosylated products (5-6). The isolated and biotransformed compounds were tested for anti-tyrosinase activity using a mushroom tyrosinase assay. Molecular docking and quantum chemical calculations were conducted to clarify the binding mode and reactivity of the compounds. The isolated compounds were identified via NMR and HR-MS as rosmarinic acid (RA) 1, methyl rosmarinate 2, methyl isorinate 3, and pinoresinol 4′-O-β-D-glucopyranoside 4. This is the first report of isolating and identifying compounds (2-4) from the Zosteraceae family. The glycosylated compounds were identified as rosmarinic acid 4-O-α-D-glucopyranoside 5 and rosmarinic acid 3′-O-α-D-glucopyranoside 6. Among all compounds, (4-6) showed significant tyrosinase inhibition, with rates of 55.5%, 22.3%, and 30.8%, respectively, compared to arbutin. The two glycosylated products exhibited better anti-tyrosinase activity than 1. In silico results aligned with in vitro findings. This study highlights Z. marina’s potential as a source of polyphenolic compounds with significant anti-aging activity, emphasizing the discovery of new anti-aging ingredients to enhance quality of life.