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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 5 of 9

               edema, expression of pro-inflammatory cytokines, apoptosis, and MMP activity. Moreover, PCP-treated
               mice showed increases in water, collagen type I, and hyaluronic acid contents in the skin, indicating a skin
               moisturizing effect.

               Resveratrol (Grape seed, grape peel, and red wine)
                                                                                             [28]
               Resveratrol is a stilbenoid compound belonging to the non-flavonoid class of polyphenols . It is present
                                                      [7]
               in grape seeds, grape peels, as well as red wine . In terms of photoprotection, resveratrol has demonstrated
               anti-oxidant, anti-inflammatory, and anti-tumor effects in several in vitro, animal, and human studies .
                                                                                                     [8]
                                               [29]
               In an in vitro study by Zhou et al. , pre-treatment of cultured human keratinocytes with different
               concentrations of resveratrol prior to UVB irradiation resulted in concentration-dependent increase in
               cell viability and a decreased rate of apoptosis. Following UVB irradiation, samples that were pre-treated
               with resveratrol had 15%-52% more viable cells and 15%-22% less apoptosis than non-treated samples.
               Furthermore, resveratrol pre-treated samples demonstrated a 1.4-fold increase in expression of Bcl-2 (anti-
               apoptotic protein), and decreased expression of Bax and caspase-3 (i.e., pro-apoptotic proteins) by 52% and
               45%, respectively.

               In mice, topical application of resveratrol prior to UVB radiation exposure was found to inhibit UVB-
               induced skin edema, inflammation, generation of ROS (e.g., hydrogen peroxide and lipoperoxides),
               and induction of COX and ornithine carboxylase . Meanwhile, oral administration demonstrated anti-
                                                          [8]
               tumor effect through alteration of tumor growth factor beta and NF-κB, both of which are involved in cell
               proliferation and tumorigenesis .
                                          [1,7]
               In humans, resveratrol has been found to afford partial protection against UVR-induced photodamage.
                       [30]
               Wu et al.  conducted a study on 15 healthy volunteers who were subject to repetitive UVR exposure
               from a solar simulator at a dose of 1.5 MED. Results showed that skin sites which were treated with topical
               resveratrol had less UV-induced erythema and sunburn cell formation compared to placebo (vehicle only)
               or negative control (no treatment).


               Curcumin (Turmeric)
               Curcumin is the active constituent of turmeric (Curcuma longa), a rhizomatous plant native to South Asia
               that is now grown in many tropical and subtropical regions worldwide. Turmeric is commonly used as a
               spice, coloring agent, and for various indications in Ayurvedic and traditional Chinese medicine [8,14] .

               Previous in vitro studies utilizing human keratinocytes and epidermoid carcinoma cells (i.e., squamous
               cell carcinoma cell line) have found that curcumin decreases UVB-induced apoptosis and inflammation
               through inhibition of the NF-κB and MAPK pathways [8,14] . In keratinocytes and fibroblasts, curcumin
               decreases the expression of MMP-1, which may help reduce the appearance of wrinkles in photoaged
                   [8]
               skin . Moreover, curcumin has demonstrated ability to decrease squamous cell carcinoma tumor growth
                     [14]
               in mice .
               Curcumin may also confer protection against UVA-mediated photodamage. According to a study by Liu et al.
                                                                                                        [31]
               (2018), pre-treatment with curcumin 2 h prior to UVA exposure prevented accumulation of ROS and
               restores the innate antioxidant function of human fibroblasts in vitro. In addition, curcumin was shown to
               mitigate UVA-induced apoptosis, inflammation, and collagen degradation.

               Silymarin (Milk thistle)
               Silymarin is an isoflavone derived from the seeds of the milk thistle plant (Silybum marianum), which
               is one of the oldest known medicinal herbs used in traditional European medicine. Nowadays, it is
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