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Torres et al. Plast Aesthet Res 2020;7:57  I  http://dx.doi.org/10.20517/2347-9264.2020.87                                       Page 3 of 9

               Results showed that Fernblock® was by far the most active (> 5x on fibroblasts and > 3x on keratinocytes)
                                                                                                 [10]
               compared to the other five PLE preparations, of which two were found to have almost no activity .

               PLE augments the body’s natural antioxidant system and minimizes the accumulation of ROS in the skin.
               It has the unique ability to scavenge superoxide anion in contrast to conventional antioxidants, which can
                                          [7]
               neutralize singlet oxygen only . As an anti-inflammatory compound, PLE has been shown to suppress
                                                                                       [7]
               UV-induced erythema and reduce cutaneous phototoxicity from photochemotherapy . It can also increase
               the minimal erythema dose (MED), the UVR dose required for immediate pigment darkening, and the
                                           [9]
               minimal phototoxic UVR dose . One randomized controlled trial found that healthy human subjects
               who took oral PLE supplements 240 mg twice daily for 60 days were 6 times less likely to have a sunburn,
               22 times more likely to have increased MED, and 15 times less likely to exhibit visible erythema post-
               UVB exposure . These effects were quantified in a later study by Kohli et al.  where it was noted that the
                            [11]
                                                                                [12]
               intensity of UVB-induced erythema decreased by an average of 8% post-PLE supplementation. Similarly,
               one study which did not utilize Fernblock®, noted increased MED among subjects with skin phototype I-III
                                                                                  [13]
               following once daily intake of an oral supplement containing PLE for 12 weeks . The possible mechanism
               underlying PLE’s anti-inflammatory properties include the inhibition of transcription factors and cytokines
               that mediate photoinflammation, namely, tumor necrosis factor (TNF), inducible nitric oxide synthase
               (iNOS), activator protein 1 (AP-1), and nuclear factor kappa B (NF-κB). In addition, PLE can also reduce
               the expression of COX-2 and prostaglandin E2, both of which are involved in the initial steps of the
                                  [1,7]
               inflammatory pathway .
               In terms of immunomodulation, PLE has been found to preserve epidermal Langerhans cells that are
                                                [7]
               otherwise depleted as a result of UVR . Its anti-tumor effects were exhibited in mice that were given oral
                                                                                        [14]
               PLE daily as evidenced by increased expression of the tumor suppressor protein p53 . PLE has likewise
               been shown to accelerate extracellular matrix turnover and promote renewal of dermal collagen through
               inhibition of matrix metalloproteinases (MMPs) and upregulation of tissue inhibitor of metalloproteinase,
                                                                 [1,8]
               thereby supporting its role in the prevention of photoaging .

                                                                                                       [15]
               PLE can also provide photoprotection from wavelengths beyond UV. In a study by Mohammad et al. ,
               patients taking 480 mg of PLE daily demonstrated a substantial decrease in visible light-induced persistent
                                                                                             [16]
               pigment darkening and delayed tanning. Furthermore, an in vitro study by Zamarrón et al.  showed that
               PLE decreased cell death and collagen degradation in human dermal fibroblasts that were exposed to visible
               light and near infrared radiation. Additional benefits of PLE include suppression of photodermatoses
               such as polymorphous light eruption and solar urticaria. It can also be used as an adjunctive treatment for
                                                                                                       [14]
               vitiligo and actinic keratosis in combination with phototherapy and photodynamic therapy, respectively .
               PLE has relatively minor side effects, including mild to moderate gastrointestinal symptoms and pruritus,
               which have been reported in a small percentage of patients receiving doses ranging from 120 mg to 1,080 mg
                   [17]
               daily . No changes in physical examination, vital signs, and laboratory tests (complete metabolic panel
               and clotting studies) were observed from baseline among patients taking 480 mg daily of PLE for 2 months .
                                                                                                       [11]
               Green tea
               Produced from the leaves and leaf buds of Camellia sinensis, green tea is one of the most widely consumed
               beverages in the world. Its many benefits are primarily due to its polyphenols - otherwise known as green
               tea catechins (GTC) - of which the most abundant (65%) is epigallocatechin-3-gallate [7,8,14] . Similar to other
               phenolic compounds, GTC has antioxidant, anti-inflammatory, immunomodulatory, and chemopreventive
               properties.


               In vitro studies on human keratinocytes have shown that GTCs can inhibit activation of AP-1 and NF-κB,
               decrease UVB-induced apoptosis, and stimulate the production of interleukin (IL)-12. IL-12 is postulated
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