Chemical Profiling and Tyrosinase Inhibition Mechanism of Phenylethanoid Glycosides from <i>Corallodiscus flabellatus</i>.

Abstract

Alpine plants face intense ultraviolet (UV) radiation in high-altitude ecosystems, necessitating adaptive mechanisms like tyrosinase-mediated phenolic metabolism for UV protection. This study aimed to characterize the phenolic profile of <i>Corallodiscus flabellatus</i> (or <i>C. flabellata</i>) and elucidate its mechanistic interactions with tyrosinase under high-altitude environments with intense ultraviolet (UV) radiation. Two novel phenylethanoid glycosides (PhGs) and seven known compounds were isolated using silica gel, ODS, and preparative HPLC, with structures determined via NMR, HR-ESI-MS, and acid hydrolysis. Tyrosinase (EC 1.14.18.1) inhibition assays revealed divergent effects: compound <b>7</b> (containing a caffeoyl moiety) exhibited potent inhibition (IC₅₀ = 0.23 μM), comparable to arbutin, while other PhGs displayed activation or biphasic responses. Molecular docking analysis demonstrated that compound <b>7</b> stabilized tyrosinase via π-π stacking with Phe264 and Cu²⁺ coordination, whereas activating compounds likely acted as substrates. These findings elucidate the dual regulatory function of PhGs, which activate tyrosinase to counteract acute ultraviolet-induced stress and inhibit its activity to attenuate oxidative overload, thereby advancing our understanding of alpine plant adaptation mechanisms.