Department of Pharmacy, Università degli Studi di Napoli Federico II, 80131 Naples, Italy.
Department of Organic Chemistry and Technology, Faculty of Chemical Technology and Biotechnology, Budapest University of Technology and Economics, Müegyetem rkp. 3, H-1111 Budapest, Hungary.
Int J Mol Sci. 2024 Jul 3;25(13):7310. doi: 10.3390/ijms25137310.
Metabolites resulting from the bacterial fermentation of dietary fibers, such as short-chain fatty acids, especially butyrate, play important roles in maintaining gut health and regulating various biological effects in the skin. However, butyrate is underutilized due to its unpleasant odor. To circumvent this organoleptic unfavorable property, phenylalanine butyramide (PBA), a butyrate precursor, has been synthesized and is currently available on the market. We evaluated the inhibition of mushroom tyrosinase by butyrate and PBA through in vitro assays, finding IC values of 34.7 mM and 120.3 mM, respectively. Docking calculations using a homology model of human tyrosinase identified a putative binding mode of PBA into the catalytic site. The anti-aging and anti-spot efficacy of topical PBA was evaluated in a randomized, double-blind, parallel-arm, placebo-controlled clinical trial involving 43 women affected by photo-damage. The results of this study showed that PBA significantly improved skin conditions compared to the placebo and was well tolerated. Specifically, PBA demonstrated strong skin depigmenting activity on both UV and brown spots (UV: -12.7% and -9.9%, Bs: -20.8% and -17.7% after 15 and 30 days, respectively, < 0.001). Moreover, PBA brightened and lightened the skin (ITA°: +12% and 13% after 15 and 30 days, respectively, < 0.001). Finally, PBA significantly improved skin elasticity (Ua/Uf: +12.4% and +32.3% after 15 and 30 days, respectively, < 0.001) and firmness (Uf: -3.2% and -14.9% after 15 and 30 days, respectively, < 0.01).
膳食纤维经细菌发酵产生的代谢产物，如短链脂肪酸，特别是丁酸盐，在维持肠道健康和调节皮肤的各种生物学效应方面发挥着重要作用。然而，由于丁酸盐气味难闻，其应用受到限制。为了规避这种不良的感官特性，可以合成丁酸盐的前体苯丙氨酸丁酰胺（PBA），目前已在市场上销售。我们通过体外试验评估了丁酸盐和 PBA 对蘑菇酪氨酸酶的抑制作用，发现它们的 IC50 值分别为 34.7 mM 和 120.3 mM。使用人酪氨酸酶同源模型进行对接计算，确定了 PBA 进入催化部位的可能结合模式。在一项涉及 43 名受光损伤影响的女性的随机、双盲、平行臂、安慰剂对照临床试验中，评估了局部应用 PBA 的抗衰老和祛斑功效。该研究结果表明，与安慰剂相比，PBA 显著改善了皮肤状况，且具有良好的耐受性。具体而言，PBA 对 UV 和棕色斑均具有较强的皮肤脱色活性（UV：15 天和 30 天分别为-12.7%和-9.9%，Bs：-20.8%和-17.7%，均<0.001）。此外，PBA 能提亮和美白肤色（15 天和 30 天分别为 ITA°+12%和+13%，均<0.001）。最后，PBA 显著改善了皮肤弹性（Ua/Uf：15 天和 30 天分别为+12.4%和+32.3%，均<0.001）和紧实度（Uf：15 天和 30 天分别为-3.2%和-14.9%，均<0.01）。
