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      Cinnamomum cassia Essential Oil Inhibits α-MSH-Induced Melanin Production and Oxidative Stress in Murine B16 Melanoma Cells

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          Abstract

          Essential oils extracted from aromatic plants exhibit important biological activities and have become increasingly important for the development of aromatherapy for complementary and alternative medicine. The essential oil extracted from Cinnamomum cassia Presl (CC-EO) has various functional properties; however, little information is available regarding its anti-tyrosinase and anti-melanogenic activities. In this study, 16 compounds in the CC-EO have been identified; the major components of this oil are cis-2-methoxycinnamic acid (43.06%) and cinnamaldehyde (42.37%). CC-EO and cinnamaldehyde exhibited anti-tyrosinase activities; however, cis-2-methoxycinnamic acid did not demonstrate tyrosinase inhibitory activity. In murine B16 melanoma cells stimulated with α-melanocyte-stimulating hormone (α-MSH), CC-EO and cinnamaldehyde not only reduced the melanin content and tyrosinase activity of the cells but also down-regulated tyrosinase expression without exhibiting cytotoxicity. Moreover, CC-EO and cinnamaldehyde decreased thiobarbituric acid-reactive substance (TBARS) levels and restored glutathione (GSH) and catalase activity in the α-MSH-stimulated B16 cells. These results demonstrate that CC-EO and its major component, cinnamaldehyde, possess potent anti-tyrosinase and anti-melanogenic activities that are coupled with antioxidant properties. Therefore, CC-EO may be a good source of skin-whitening agents and may have potential as an antioxidant in the future development of complementary and alternative medicine-based aromatherapy.

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          Most cited references48

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          Cyclic AMP a key messenger in the regulation of skin pigmentation.

          Compelling evidence has been gathered indicating that pro-opiomelanocortin peptides, alpha-melanocyte stimulating hormone (alpha-MSH) and adrenocorticotropic hormone (ACTH), through the cyclic AMP pathway, play a pivotal role in melanocyte differentiation and in the regulation of melanogenesis. Recently, the molecular events linking cAMP to melanogenesis up-regulation have been elucidated. This cascade involves the activation of protein kinase A and CREB transcription factor, leading to the up-regulation of the expression of Microphthalmia associated transcription factor (MITF). MITF has been found mutated in patients with Waardenburg syndrome 2A, and plays a crucial role in melanocyte development. MITF binds and activates melanogenic gene promoters, thereby increasing their expression which results in an increased melanin synthesis. Beyond this simplified scheme, It appears that melanogenic gene expression is controlled by a complex network of regulation involving other transcription factors such as Brn2, TBX2, PAX3 and SOX10. Further studies are required to better understand the respective roles of these factors in the regulation of melanin synthesis. In addition, other intracellular signaling pathways, like the phosphatidyl inositol 3-kinase pathway, as well as the molecular cascade of events governed by the small GTP-binding protein Rho, seem to be involved in the regulation of melanogenesis and melanocyte dendricity. Finally, it should be mentioned that cAMP activates a melanocyte-specific pathway leading to MAP kinase activation. MAP kinase, ERK2, phosphorylates MITF, thereby targeting the transcription factor to proteasomes for degradation. Thus, in addition to the complex transcriptional regulation, melanogenesis is also subjected to a post-translational regulation that controls MITF or tyrosinase function. Taken together, these complex molecular processes would finally allow a fine tuning of melanocyte differentiation leading to melanin synthesis.
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            Mushroom tyrosinase: recent prospects.

            Tyrosinase, also known as polyphenol oxidase, is a copper-containing enzyme, which is widely distributed in microorganisms, animals, and plants. Nowadays mushroom tyrosinase has become popular because it is readily available and useful in a number of applications. This work presents a study on the importance of tyrosinase, especially that derived from mushroom, and describes its biochemical character and inhibition and activation by the various chemicals obtained from natural and synthetic origins with its clinical and industrial importance in the recent prospects.
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              Antimelanogenic and antioxidant properties of gallic acid.

              To find novel skin-whitening agents, the melanogenesis inhibitory action of gallic acid (GA) was investigated. In this current study, the effects of GA on mushroom tyrosinase, tyrosinase inhibitory activity, and melanin content were assessed in B16 melanoma cells (B16 cells). Results indicated that GA has a strong antityrosinase activity (IC50=3.59x10(-6) M). Furthermore, data on murine tyrosinase activity and melanin biosynthesis revealed that GA effectively suppressed murine tyrosinase action and the amount of melanin. To investigate the relation between GA's inhibition of melanogenesis and antioxidant activity, the effect of GA on reactive species (RS) generation and the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio in were determined in B16 cells. Results indicated that GA effectively down-regulated the RS generation and enhanced the GSH/GSSG ratio. Based on these results, I propose that GA exerts antimelanogenic activity coupled with antioxidant properties by suppressing RS generation and maintaining a higher GSH/GSSG ratio.
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                Author and article information

                Journal
                Int J Mol Sci
                Int J Mol Sci
                ijms
                International Journal of Molecular Sciences
                Molecular Diversity Preservation International (MDPI)
                1422-0067
                September 2013
                18 September 2013
                : 14
                : 9
                : 19186-19201
                Affiliations
                [1 ]Department of Food and Nutrition, Providence University, 200, Sec. 7, Taiwan Boulevard, Shalu Dist., Taichung City 43301, Taiwan; E-Mails: stchou@ 123456pu.edu.tw (S.-T.C.); ctchang@ 123456pu.edu.tw (C.-T.C.)
                [2 ]Department of Cosmetic Science, Providence University, 200, Sec. 7, Taiwan Boulevard, Shalu Dist., Taichung City 43301, Taiwan; E-Mails: g9924002@ 123456gmail.com (W.-L.C.); g1000208@ 123456pu.edu.tw (Y.-C.L.)
                [3 ]Department of Applied Chemistry, Providence University, 200, Sec. 7, Taiwan Boulevard, Shalu Dist., Taichung City 43301, Taiwan
                [4 ]Department of Education and Research, Taichung Veterans General Hospital, 1650, Sec. 4, Taiwan Boulevard, Taichung City 40705, Taiwan; E-Mail: h2326@ 123456vghtc.gov.tw
                Author notes
                [* ]Author to whom correspondence should be addressed; E-Mail: yingshih@ 123456pu.edu.tw ; Tel.: +886-4-2632-8001 (ext. 15471); Fax: +886-4-2631-1167.
                Article
                ijms-14-19186
                10.3390/ijms140919186
                3794828
                24051402
                f1730746-9fc9-49c0-be4f-d403c0bafc38
                © 2013 by the authors; licensee MDPI, Basel, Switzerland

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : 29 July 2013
                : 28 August 2013
                : 29 August 2013
                Categories
                Article

                Molecular biology
                cinnamomum cassia presl,essential oil,cinnamaldehyde,tyrosinase,melanin,antioxidant
                Molecular biology
                cinnamomum cassia presl, essential oil, cinnamaldehyde, tyrosinase, melanin, antioxidant

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