Abstract
In this study, the anti-melanogenic effects of Heracleum moellendorffii Hance extract (HmHe) and the mechanisms through which it inhibits melanogenesis in melan-a cells were investigated. Mushroom tyrosinase (TYR) activity and melanin content as well as cellular tyrosinase activity were measured in the cells. mRNA and protein expression of microphthalmia-associated transcription factor (MITF), tyrosinase (TYR), TYR-related protein-1 (TYRP-1) and -2 were also examined. The results demonstrate that treatment with HmHe significantly inhibits mushroom tyrosinase activity. Furthermore, HmHe also markedly inhibits melanin production and intracellular tyrosinase activity. By suppressing the expression of TYR, TYRP-1, TYRP-2, and MITF, HmHe treatment antagonized melanin production in melan-a cells. Additionally, HmHe interfered with the phosphorylation of extracellular signal-regulated kinase (ERK) 1/2, with reversal of HmHe-induced melanogenesis inhibition after treatment with specific inhibitor U0126. In summary, HmHe can be said to stimulate ERK1/2 phosphorylation and subsequent degradation of MITF, resulting in suppression of melanogenic enzymes and melanin production, possibly due to the presence of polyphenolic compounds.
Highlights
Melanin, the major determining factor for skin color, provides a defense system against the harmful effects of ultraviolet (UV)-induced skin damage
Previous studies have informed that increased reactive oxygen species (ROS)/reactive nitrogen species (RNS) generation induced by ultraviolet radiation (UVR) correlates with an elevation in melanogenesis, possibly via the upregulation of tyrosinase activity, and protein and mRNA levels in melanocyte cells [5]
Previous studies revealed that UVR-induced ROS/RNS generation interfered with melanogenesis, and contributed to melanocyte proliferation and transformation, which leads to melanogenesis [7]
Summary
The major determining factor for skin color, provides a defense system against the harmful effects of ultraviolet (UV)-induced skin damage. UV-induced melanin biosynthesis primarily results in the production of pheomelanin and induces the continuous generation of reactive oxygen species (ROS), including hydrogen peroxide (H2O2), hydroxyl radicals, and superoxide radicals in melanocytes [3] Oxidative intermediates such as reactive quinones, which are damaging to cellular proteins and DNA, are generated during melanogenesis [4]. Whitening products containing potent tyrosinase inhibitors have severe side effects, including high cellular toxicity and low oxygen and water stability, limiting their application Due to their low toxicity and side effect profile, natural biomaterials are under substantial consideration in the development of an effective and safe skin-depigmenting agent in the field of cosmetic and cosmeceutical industry. To develop novel and useful inner beauty-purpose nutraceuticals, the present study evaluated the effects of HmHe extracts in the context of melanin production in a melanocyte cell culture system, and for the first time, the underlying mechanism by which an extract of HmHe mitigates the production of melanin was determined: HmHe downregulates melanogenesis factors in melan-a cells by activating extracellular signal-regulated kinase (ERK)1/2 signaling pathways
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