Abstract
Tyrosinase is the central enzyme involved in the highly complex process of melanin formation, catalyzing the rate-limiting steps of this biosynthetic pathway. Due to such a preponderant role, it has become a major target in the treatment of undesired skin pigmentation conditions and also in the prevention of enzymatic food browning. Numerous phenolic-based structures from natural sources have been pointed out as potential tyrosinase inhibitors, including anthocyanins. The aim of the present study was to individually assess the tyrosinase inhibitory activity of eight purified compounds with a variable degree of structural complexity: native anthocyanins, deoxyanthocyanins, and pyranoanthocyanins. The latter two, the groups of anthocyanin-related compounds with enhanced stability, were tested for the first time. Compounds 1 to 4 (luteolinidin, deoxymalvidin, cyanidin-, and malvidin-3-O-glucoside) revealed to be the most effective inhibitors, and further kinetic studies suggested their inhibition mechanism to be of a competitive nature. Structure–activity relationships were proposed based on molecular docking studies conducted with mushroom tyrosinase (mTYR) and human tyrosinase-related protein 1 (hTYRP1) crystal structures, providing information about the binding affinity and the different types of interactions established with the enzyme’s active center which corroborated the findings of the inhibition and kinetic studies. Overall, these results support the applicability of these compounds as pigmentation modulators.
Highlights
Major efforts have been made in the search for tyrosinase inhibitors, as this has proven to be an effective strategy to ameliorate the aesthetic appearance of the skin and to prevent the undesired enzymatic browning phenomena of food products, which compromises their sensory and nutritional properties, and to date, a myriad of inhibitors have been explored for those purposes
Some representative compounds of three different but structurally related pigments were evaluated for their tyrosinase inhibitory capacity: deoxyanthocyanins, anthocyanins, and pyranoanthocyanins (Figure 1)
The results presented suggest that the different anthocyanins and related structures tested have concrete ways of interacting with tyrosinase, and by studying each compound individually, it was possible to draw some conclusions about the effect of different structural features on their modulating effect
Summary
The type and degree of pigment production and distribution determines the eye, hair, and constitutive skin color [1,2]. In addition to its coloring effect, the importance of the pigment relies on its capacity to form a supranuclear melanin cap within skin keratinocytes, absorbing UV radiation and dissipating most of the absorbed energy as heat, protecting the skin against UV-induced oxidative stress and cellular damage [3,4]. Despite the acknowledged photoprotective effects of melanin, its aberrant production, secretion, and accumulation is related to several hyperpigmentary skin disorders, such as solar lentigines, melasma, and post-inflammatory hyperpigmentation, while being reported as a risk factor for melanoma development [5]. In the context of skin applications, certain conventional lightening agents have long been in the spotlight of controversy: kojic acid, for instance, is associated with possible side effects such as dermatitis and erythema, while hydroquinone has been banned by EU Cosmetic Regulation [8,9]
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