Photochemoprotective Potential of the Ethyl Acetate Fraction from Eugenia hiemalis Leaves and Its 2,6-Di-O-galloylarbutin Isolate Against UVB-Induced Photodamage.

Intense and constant exposure to UVB radiation can lead to inflammation and oxidative stress, which are associated with many cutaneous disorders, including photoaging and skin cancer. Antioxidant plant materials that are rich in polyphenols, such as the ethyl acetate fraction (EAF) from Eugenia hiemalis leaves, and phenolic compounds represent a promising approach to protect the skin against UVB-induced damage. The present study evaluated the photochemoprotective potential of the EAF and its 2,6-di-O-galloylarbutin (1) isolate. The EAF and the phenolic antioxidant (1) reduced UVB-induced L929 fibroblast death. The EAF prevented UVB-induced damage in fibroblasts by inhibiting the intracellular production of reactive oxygen species and lipid peroxidation, especially in pretreated cells. Topical treatment with an emulsion with 1% EAF prevented/attenuated UVB-induced inflammation and oxidative stress in the skin in hairless mice by controlling the increase in myeloperoxidase activity, reducing superoxide anion production, maintaining radical-scavenging ability and ferric reducing power, and controlling the depletion of reduced glutathione and catalase levels. The EAF also inhibited the increase in epidermal thickness, mast cell infiltration, the number of sunburn cells and collagen fiber destruction that were triggered by UVB. The in vitro and in vivo results indicated that the EAF is a bioactive agent that is able to protect the skin against the harmful effects of UVB.

Evaluation of lipid nanoparticles for topical delivery of protocatechuic acid and ethyl protocatechuate as a new photoprotection strategy.

Excessive exposure to solar radiation induces injurious effects on human skin. Our previous study evidenced that protocatechuic acid (P0) and ethyl protocatechuate (P2) act against photodamage and photoaging. The present study aimed to develop solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLCs) for topical delivery of P0 or P2, as a strategy for photoprotection. Lipid nanoparticles exhibited mean particle size, polydispersity index, zeta potential and association efficiency between 200 and 400 nm, 0.160 to 0.460, -2.2 to -5.2 mV, and 60% to 80%, respectively. The formulations were stable for 3 months when stored at 4○C and 25○C/60% RH. SLNs/NLCs-P0 showed minor cytotoxicity effects compared with SLNs/NLCs-P2, in HaCat (keratinocytes) and HFF-1 (fibroblasts) cell lines. Additionally, bare NLCs exhibited less cytotoxicity effect, compared with bare SLNs. NLCs exhibited a controlled in vitro release of P0 and P2, and were able to protect the compounds against UVB degradation. Ex vivo permeability study showed that NLCs modulated P0 and P2 retention profiles on human skin layers. Furthermore, histological analysis of skin showed that NLCs-P0 did not cause morphological alterations, while NLCs-P2 showed a potential irritation effect in the skin structure. Based on these results, NLCs were considered a potential dermatological nanocarrier for P0 delivery.

Abilities of protocatechuic acid and its alkyl esters, ethyl and heptyl protocatechuates, to counteract UVB-induced oxidative injuries and photoaging in fibroblasts L929 cell line.

Ultraviolet B (UVB) radiation triggers the activation of many reactive oxygen species (ROS)-sensitive signaling pathways, resulting in the induction of skin damage that can progress to premature skin aging with long-term exposure. Even after the cessation of UVB radiation, the activated photosensitizers can still cause cellular injury. Thus, the use of photoprotectors that inhibit or prevent intracellular ROS production during or after UV exposure is one alternative to counteract UV-induced oxidative damage. The present study investigated the photoprotective activity of protocatechuic acid (P0) and its alkyl esters ethyl protocatechuate (P2) and heptyl protocatechuate (P7) against UVB-induced damage in L929 fibroblasts by evaluating biomarkers of oxidative stress and photoaging. P0, P2 and P7 markedly increased cell viability after UVB exposure. This protective effect was related to the ability of these compounds to absorb UVB and restore cellular redox balance even 24 h after UVB exposure. P0, P2 and P7 also decreased oxidative damage to membrane lipids, mitochondrial membrane potential, and DNA. They also inhibited the nuclear translocation of NF-κB p65 and downregulated the expression of the photoaging-related proteins matrix metalloproteinases-1 and -9 and cyclooxygenase-2. As the lipophilicity of the P0 derivatives increased, their antioxidant potency increased, but more pronounced cytotoxic effects were also detected. In summary, P0 and P2 may be promising candidates for the prevention and treatment of UVB-induced skin photodamage and photoaging.