Photoprotection and Skin Pigmentation: Melanin-Related Molecules and Some Other New Agents Obtained from Natural Sources

Abstract

Direct sun exposure is one of the most aggressive factors for human skin. Sun radiation contains a range of the electromagnetic spectrum including UV light. In addition to the stratospheric ozone layer filtering the most harmful UVC, human skin contains a photoprotective pigment called melanin to protect from UVB, UVA, and blue visible light. This pigment is a redox UV-absorbing agent and functions as a shield to prevent direct UV action on the DNA of epidermal cells. In addition, melanin indirectly scavenges reactive oxygenated species (ROS) formed during the UV-inducing oxidative stress on the skin. The amounts of melanin in the skin depend on the phototype. In most phenotypes, endogenous melanin is not enough for full protection, especially in the summertime. Thus, photoprotective molecules should be added to commercial sunscreens. These molecules should show UV-absorbing capacity to complement the intrinsic photoprotection of the cutaneous natural pigment. This review deals with (a) the use of exogenous melanin or melanin-related compounds to mimic endogenous melanin and (b) the use of a number of natural compounds from plants and marine organisms that can act as UV filters and ROS scavengers. These agents have antioxidant properties, but this feature usually is associated to skin-lightening action. In contrast, good photoprotectors would be able to enhance natural cutaneous pigmentation. This review examines flavonoids, one of the main groups of these agents, as well as new promising compounds with other chemical structures recently obtained from marine organisms.

Keywords: antioxidant natural products; flavonoids.; melanin; photoprotection; sunscreen.

Figure 1

Solar radiation reaching Earth’s surface, skin penetrance, and biological effects. (A) Approximate percentage (%) of the total solar radiation reaching Earth’s surface for different wavelength regions. (B) Skin penetrance of UVB and UVA. Note that the less energetic UVA radiation has deeper penetrance than UVB. The main cellular consequences are also mentioned.

Figure 2

Graphic representation of a detail of the epidermis. It contains layers with abundant keratinocytes and some other cell types. Melanocytes are mostly found in the epidermal–dermal junction. Melanocytes are the only cells able to synthesize melanin. These cells have dendrites along the keratinocytes of their melano-epidermal units to facilitate the transport and transference of melanosomes filled with melanin. The image on the right shows one melanocyte transferring melanosomes (melanin granules, black dots) to surrounding keratinocytes of the melano-epidermal unit.

Figure 3

Schematic pathway of eumelanogenesis and pheomelanogenesis. Tyr is tyrosinase, the key enzyme catalyzing the rate-limiting step of the pathway, the oxidation of L-tyrosine to L-dopaquinone. Tyrp1 and Tyrp2 are involved in catalytic actions at the final phase of eumelanogenesis (left). Reactive oxygenated species accelerate the polymerization of indole units to eumelanin. Tyrps can also act as stabilizers of tyrosinase. On the other hand, dopaquinone is a pivotal branch point and can react with thiol-containing products, such as L–cysteine or glutathione (GSH), to lead the pathway to phaeomelanin through the intermediates cysteinyl-dopa and benzothiazine compounds (right). DHI, 5,6-dihydroxyindole; DHICA, 5,6-dihydroxyindole-2-carboxylic acid; IQ, 5,6-indolequinone; IQCA, indolequinone-2-carboxylic acid.

Figure 4

Structure of the precursor units (dopa, dopamine), the oxidized cyclized indole derivatives, DHI and DHICA, and a simplified model of eumelanin and polydopamine. Natural eumelanin might be considered a DHICA and DHI polymer. Polymerization occurs mainly through positions 4 and 7 since the presence of carboxyl groups blocks position 2 and greatly deactivates position 3. The size and light absorption of eumelanin depends on the DHI/DHICA ratio. The polydopamine model might be considered as a polymer of only DHI, more branched through positions 2, 3, 4, and 7. These are oversimplified models, since other uncycled units can be incorporated to the polymer during the uncontrolled formation of the pigments.

Figure 5

(a) General structure of the flavonoid framework with the four main types of flavonoids; (b) other flavonoid-related frameworks; (c) particular plant compounds and (d) marine compounds used in cosmeceutics (see Table 1). (a) The second line includes the four main types of flavonoids: flavonols, flavones, flavanones, and flavanols. (b) Flavonoid-related structure of the isoflavonoid framework (ring B is bound to position 3) and chalcone; (c) two important plant compounds, epigallocatechin-3-gallate (EGCG) found in green tea and resveratrol found in grape vine; (d) marine topsentin from a sponge and palythine from coral.