norbixin and crocin

Age-related macular degeneration (AMD) is the commonest cause of severe visual loss and blindness in developed countries among individuals aged 60 and older. AMD slowly progresses from early AMD to intermediate AMD (iAMD) and ultimately late-stage AMD. Late AMD encompasses either neovascular AMD (nAMD) or geographic atrophy (GA). nAMD is defined by choroidal neovascularization (CNV) and hemorrhage in the subretinal space at the level of the macula. This induces a rapid visual impairment caused by the death of photoreceptor cells. Intravitreal injection of anti-vascular endothelial growth factor (VEGF) antibodies is the standard treatment of nAMD but adds to the burden of patient care. GA is characterized by slowly expanding photoreceptor, and retinal pigment epithelium (RPE) degeneration patches progressively leading to blindness. There is currently no therapy to cure GA. Late AMD continues to be an unmet medical need representing a major health problem with millions of patients worldwide. Oxidative stress and inflammation are recognized as some of the main risk factors to developing late AMD. The antioxidant formulation AREDS (Age-Related Eye Disease Studies), contains

Topics: Aged; Aged, 80 and over; Anti-Inflammatory Agents; Antioxidants; Carotenoids; Disease Progression; Humans; Macular Degeneration; Middle Aged; Retinal Pigment Epithelium; Severity of Illness Index

In this present study, the inhibitory mechanism of three selected apocarotenoids (bixin, norbixin and crocin) on the diphenolase activity of tyrosinase has been investigated. The preliminary screening results indicated that apocarotenoids inhibited tyrosinase activity in a dose-dependent manner. Kinetic analysis revealed that apocarotenoids reversibly inhibited tyrosinase activity. Analysis of fluorescence spectra showed that apocarotenoids quenched the intrinsic fluorescence intensity of the tyrosinase. Further, molecular docking results implied that apocarotenoids were allosterically bound to tyrosinase through hydrophobic interactions. The results of the in vitro studies suggested that higher concentrations of bixin and norbixin inhibited tyrosinase activity in B16F0 melanoma cells. Our results suggested that apocarotenoids could form the basis for the design of novel tyrosinase inhibitors.

Topics: Allosteric Site; Animals; Carotenoids; Cell Line, Tumor; Dose-Response Relationship, Drug; Hydrophobic and Hydrophilic Interactions; Kinetics; Melanins; Melanoma; Mice; Molecular Docking Simulation; Monophenol Monooxygenase; Protein Binding; Spectrometry, Fluorescence