Anti-tyrosinase, antioxidant and UV-protective agents obtained from natural sources: A high-throughput bioguided approach

Abstract

Tyrosinase is regarded as a target enzyme in skin-whitening and in therapeutic interventions for dermatological disorders associated with melanin hyperpigmentation. Abnormal melanin pigments are an aesthetic problem prevalent in middle-aged and elderly individuals [1], but may also occur upon UV radiation [2]. Skin ageing on the other hand, is associated with free radical formation and UV light exposure through activation of the reactive oxygen species (ROS) system [3]. Since many known agents have been proven toxic [4], tyrosinase inhibitors and antioxidant compounds from natural sources are in the center of research interest for the development of cosmeceutical products.This project with the acronym AGROCOS (FP7) aimed to carry to the stage of development candidates, plant derived small molecules with skin-whitening, antioxidant and UV-protective properties. 460 natural compounds with structurally diverse scaffolds and decoration patterns were evaluated for the above mentioned properties. The screens addressed radical scavenging properties, protection against reactive oxygen species (ROS) and UV-induced cell death in cell-based assays, and anti-tyrosinase properties. Based on this screening, a collection of 3600 extracts from biodiversity hotspots plants was emerged and screened on the same targets. 31 most antioxidant extracts, including many representatives from Myrtaceae and Fabaceae families, and 13 extracts with anti-tyrosinase properties, such as Glycyrrhiza glabra and Caesalpinia schlechteri were prioritized for an HPLC-based bioguided microfractionation. Active fractions were submitted to a final purification of bioactive compounds.This unique extract library combined with a high-throughput approach proved to be an efficient tool for the discovery of natural agents with antioxidant, UV-protective and anti-tyrosinase properties.