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  • AZD1208 Elastase belongs to chymotrypsin family

    2020-03-18

    Elastase belongs to chymotrypsin family of proteases and it is responsible for the breakdown of elastin and other proteins, such as collagen and fibronectin, which are fundamental for the ECM elastic properties (Imokawa and Ishida, 2015). Misregulations of this enzyme are involved in skin ageing processes (Korkmaz et al., 2010). In fact, the excessive hydrolysis of the dermal elastin fiber network leads to the loss of skin elasticity and consequent skin sagging (Thring et al., 2009). On this basis, elastase inhibitors are endowed with anti-wrinkles activity promoting the preservation of skin elasticity. Tyrosinase is a copper-containing enzyme, also known as polyphenol oxidase (PPO). It catalyzes two distinct reactions, namely: the hydroxylation of a monophenol and the conversion of an o-diphenol to the corresponding o-quinone. This enzyme is responsible for the rate-limiting first two steps of melanin biosynthetic pathway, and thus, for skin, hair, and eyes color in humans (Pillaiyar et al., 2017). Tyrosinase misregulated expression and/or activity causes skin pigmentation disorders such as: lentigo senilis, urticaria pigmentosa, and age-related skin hyperpigmentation (Slominski et al., 2004). Therefore, tyrosinase inhibitors are candidate skin-whitening agents. In this work, aimed at identifying natural products endowed with anti-ageing potential, the in vitro tyrosinase and elastase inhibitory activity of a hundred hydroalcoholic plant extracts was evaluated. Moreover, the total phenolic and flavonoid content of the tested extracts was also determined, considering the importance of these compounds as antioxidants. In order to investigate on the involvement of these AZD1208 of phytochemicals in the tested bioactivities, total phenolic and flavonoid content was also statistically correlated to the percentages of enzymatic inhibitions.
    Methods and materials
    Results A first screening of tyrosinase and elastase inhibitory activity was carried out on the extracts at the fixed concentration of 50 μg/mL. The obtained results (reported in Table 1) allowed the selection of seventeen extracts, which, at the tested concentration, highlighted a marked inhibitory activity (percentage of inhibition higher than 30%). In particular, the following samples were selected: Arbutus unedo L. (leaves), Azadirachta indica A. Juss. (leaves), Cistus monspeliensis L. (aerial parts), Cistus salvifolius L. (aerial parts), Cochlospermum tinctorium Perrier ex A. Rich. (leaves), Cytinus hypocistis (L.) L. (aerial parts), Hypericum hircinum L. (aerial parts), Hypericum scruglii Bacch., Brullo & Salmeri (areal parts), Khaya senegalensis (Desv.) A. Juss (fruits), Limonium morisianum Arrigoni (aerial parts), Myrtus communis L. (fruits and leaves), Pistacia lentiscus L. (fruits and leaves), Pistacia terebinthus L. (leaves), Vitellaria paradoxa C.F. Gaertn. (leaves and roots). Those samples were more deeply investigated by calculating the IC50 of enzymatic inhibition and comparing them by statistical analysis. Regarding elastase inhibition, the IC50 values of the twelve selected samples ranged from 7.17 ± 1.36 to 101.07 ± 20.74 μg/mL (Fig. 1A). These results are particularly interesting considering that the positive control (quercetin) showed an IC50 value of 61 μg/mL (202 μM). Among the twelve samples, the extract obtained from the leaves of Pistacia lentiscus resulted the most potent elastase inhibitor. Regarding the activity against tyrosinase, the IC50 values calculated for the sixteen most active extracts ranged from 20.35 ± 0.24 to 101.41 ± 7.46 μg/mL (Fig. 1B). The extracts of Cytinus hypocistis (aerial parts), Limonium morisianum (aerial parts) and Pistacia lentiscus (leaves) resulted the most potent and no significant differences among their IC50 values were highlighted by the statistical analysis. As highlighted by the results of the first screening (Table 1), three samples showed a percentage of tyrosinase inhibition little lower than 30%, thus, although they were not selected among the most promising plants, their IC50 was also calculated. In particular, Cassia siberiana D.C. showed an IC50 of 165 μg/mL, while Lavandula stoechas L. and Hypericum scruglii were proved only poorly active. In fact, for these two plants, even at the highest tested concentration (250 μg/mL) the percentage of inhibition was much lower than 50%.