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Page 4 of 9                                        Torres et al. Plast Aesthet Res 2020;7:57  I  http://dx.doi.org/10.20517/2347-9264.2020.87

               to play a role in photoprotection since photoinflammation, impaired DNA repair, and tumorigenesis are
               associated with an absence of IL-12. In mice, topical and oral GTC has been found to protect against
               photoinflammation and photocarcinogenesis through inhibition of the mitogen-activated protein kinase
               inflammatory pathway and upregulation of genes involved in DNA repair.

               In humans, previous studies have reported that topical GTC reduces photodamage by decreasing
               production of UVR-induced cyclobutane pyrimidine dimers (CPDs) and visible sunburn [18,19] . However,
                                                                                            [7]
               GTCs have poor skin penetration when topically applied due to their poor lipid solubility . They are also
                                        [19]
               subject to photodegradation.  In contrast, orally administered GTC has been shown to have good skin
               bioavailability as evidenced by their presence in skin biopsy specimens and skin blister fluid. This was
                                                                                        [20]
               noted after GTC supplementation equivalent to 5 cups of green tea daily for 12 weeks . However, there is
               conflicting evidence in the literature as to the efficacy of oral GTC as a photoprotectant [21,22] .

               One study showed that women who consumed one liter of green tea daily for 3 months were found to
               have increased skin elasticity, improved skin texture, decreased transepidermal water loss, and increased
                                 [22]
               cutaneous blood flow . In contrast, a study of healthy, light-skinned (skin phototype I-II) adults revealed
               no significant differences in UVR-induced erythema, dermal leukocytic infiltration, and induction of
               cyclooxygenase and lipoxygenase inflammatory pathways among those taking daily GTC supplements
                                                                              [21]
               (1,080 mg plus 100 mg vitamin C) compared to those in the placebo group . Further studies are needed to
               reconcile these conflicting evidences.

               Pomegranate
               The extract from Punica granatum or pomegranate is rich in phenolic compounds, specifically,
               anthocyanins, catechins, and tannins . Significant amounts of these compounds are present in different
                                               [7]
                                                                        [23]
               parts of the fruit but are most concentrated in the peel and juice . At present, pomegranate extract is
               widely available as an over-the-counter oral supplement or topical formulation, and is often incorporated
               in commercially sold skin care products.


               Pomegranate extract has anti-inflammatory properties and a very potent antioxidant activity - even
                                                  [7,8]
               greater than that of green tea or red wine . It confers photoprotection through inhibition of UV-induced
               production of free radicals, erythema and burning, DNA damage, cell proliferation, and apoptosis [8,24] . It
                                               [25]
               can also decrease collagen breakdown .
               Murine in vivo studies have demonstrated that topical application of pomegranate extract can replenish
               antioxidants (including catalase, peroxidase, and superoxide dismutase), as well as reduce photoinflammation.
               This was evidenced by decreased skin edema, epidermal thickening, dermal neutrophilic infiltrates,
               ornithine decarboxylase, and COX-2. Additionally, topical pomegranate extract has been found to
               prolong the latency and lessen the multiplicity of skin tumors, thereby supporting its benefit against
                                [26]
               photocarcinogenesis .
               Oral administration of pomegranate extract was found to be protective against UVB-induced skin
               cancer formation in mice through downregulation of COX-2, iNOS, cyclin D2, and MMPs. Women who
               consumed 1000 mg of pomegranate extract or 8 ounces of pomegranate juice daily for 12 weeks were
                                                                                 [25]
               reported to have increased MED in a randomized controlled, open-label study .
                                                                                                        [27]
               The anti-aging benefits of pomegranate extract were further investigated in a 2017 study by Kang et al.
               using orally administered pomegranate juice concentrated powder (PCP) in hairless mice. In this 15-week,
               placebo-controlled trial, PCP was given at 100, 200, or 400 mg/kg once daily, and 1 hour prior to thrice
               weekly UVB exposure. The investigators reported dose-dependent decreases in wrinkle formation, skin
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