| 词条 | Draft:Rhododendrol |
| 释义 |
Rhododendrol (RD) also called 4-[(3R)-3-hydroxybutyl]phenol (systemic name), is an organic compound with the formula C10H14O2. It is a naturally occurring ingredient present in many plants, such as the Betula Alba [1]. The phenolic compound was first developed in 2010 as a tyrosinase inhibitor for skin-lightening cosmetics. In 2013, after rhododendrol reportedly caused skin depigmentation in consumers using RD-containing skin-brightening cosmetics, the cosmetics were withdrawn from the market. The skin condition, caused by RD, is called RD-induced leukoderma. Rhododendrol exerts melanocyte cytotoxicity via a tyrosinase-dependent mechanism. It has been shown to impair the normal proliferation of melanocytes through reactive oxygen species-dependent activation of GADD45 [2]. It is now well established that Rhododendrol is a potent tyrosinase inhibitor [3][4]. {{Chembox |Rhododendrol||ImageFile=Rhododendrol.svg|ImageSize=200|ImageAlt=|IUPACName=4-[(3R)-3-hydroxybutyl]phenol|OtherNames=Rhododenol, RD, 4-(4-hydroxyphenyl)-2-butanol, (-)-Betuligenol, (R)-Frambinol, 4-Hydroxy-α-methyl-benzenepropanol |Section1={{Chembox Identifiers | CASNo = 501-96-2 | PubChem = 919205 | ChemSpiderID = 802471 | UNII = 97PTR2F3Z8 | ChEMBLID = CHEMBL1086681 | InChI=1S/C10H14O2/c1-8(11)2-3-9-4-6-10(12)7-5-9/h4-8,11-12H,2-3H2,1H3/t8-/m1/s1 | StdInChIKey=SFUCGABQOMYVJW-MRVPVSSYSA-N | SMILES = CC(CCC1=CC=C(C=C1)O)O | Formula = C₁₀H₁₄O₂ | MolarMass = 166.22 g/mol | Appearance = White solid powder | Density = 1.1±0.1 g/cm3 | MeltingPt = 68-71 °C | BoilingPt = 315.4±17.0 °C at 760 mmHg | Solubility = | MainHazards = cytotoxicity | GHSPictograms = {{GHS07}} | GHSSignalWord = Warning | HPhrases = {{H-phrases|302|319|}} | PPhrases = {{P-phrases|270|280|301+312|305+351+338|330|337+313|501|}} | FlashPt = 153.4±15.5 °C | AutoignitionPt = Structure and reactivityStructureRhododendrol occurs as the glucoside rhododendrin in leaves of the Rhododendron (Ericacae). The chemical compound is obtained from alkylation of phenols (C6H5OH), and has a para-substituted structure.
BiosynthesisThe synthesis of Rhododendrol can be achieved in .. steps from Rhododendrin. Mechanisms of actionThe mechanism of action of Rhododendrol has been investigated in multiple studies which revealed that RD competes with tyrosine for hydroxylation by tyrosinase and interferes with melanin synthesis [5][6][7]. First, RD is catalysed by tyrosinase to produce toxic metabolites as RD-cyclic catechol. These reactive metabolites cause damage to the melanocytes. There is still uncertainty, however, how the metabolites result in melanocyte damage. A previous report reported that the melanocyte toxicity of rhododendrol is caused by the production of cytotoxic reactive oxygen species (ROS) [2]. However, another study stated that there was no ROS detected in the with rhododendrol-treated melanocytes, but a tyrosinase-dependent accumulation of endoplasmic reticulum stress and activation of the apoptotic pathway [8][7]. Even though there is still no full agreement on the exact mechanism of action, it is suggested that the mechanism of RD-induced leukoderma closely resembles the mechanism displayed in the figure below (Suggested mechanism of Rhododendrol.png). In some individuals, a T-cell response is observed. The melanocyte cell lysates may sensitise T-cells, and the immunised cytotoxic T-lymphocytes (specific to Melan A, which is a melanocytic differentiation marker) may enhance the RD-induced leukoderma or evoke vitiligo-like lesions on the non-applied skin [5]. MetabolismEfficacy and side effectsEfficacyAdverse effectsToxicity{{Content}}References1. ^{{Cite journal|last=KUBO|first=MASAYOSHI|last2=INOUE|first2=TAKAO|last3=NAGAI|first3=MASAHIRO|date=1980|title=Studies on the constituents of aceraceae plants. III. Structure of acerogenin B from Acer nikoense Maxim.|url=http://dx.doi.org/10.1248/cpb.28.1300|journal=CHEMICAL & PHARMACEUTICAL BULLETIN|volume=28|issue=4|pages=1300–1303|doi=10.1248/cpb.28.1300|issn=0009-2363}} 2. ^1 {{Cite journal|last=Ito|first=Shosuke|last2=Ojika|first2=Makoto|last3=Yamashita|first3=Toshiharu|last4=Wakamatsu|first4=Kazumasa|date=2014-06-27|title=Tyrosinase-catalyzed oxidation of rhododendrol produces 2-methylchromane-6,7-dione, the putative ultimate toxic metabolite: implications for melanocyte toxicity|url=http://dx.doi.org/10.1111/pcmr.12275|journal=Pigment Cell & Melanoma Research|volume=27|issue=5|pages=744–753|doi=10.1111/pcmr.12275|issn=1755-1471}} 3. ^{{Cite journal|last=Gabe|first=Yu|last2=Miyaji|first2=Akimitsu|last3=Kohno|first3=Masahiro|last4=Hachiya|first4=Akira|last5=Moriwaki|first5=Shigeru|last6=Baba|first6=Toshihide|date=September 2018|title=Substantial evidence for the rhododendrol-induced generation of hydroxyl radicals that causes melanocyte cytotoxicity and induces chemical leukoderma|url=http://dx.doi.org/10.1016/j.jdermsci.2018.06.007|journal=Journal of Dermatological Science|volume=91|issue=3|pages=311–316|doi=10.1016/j.jdermsci.2018.06.007|issn=0923-1811}} 4. ^{{Cite journal|last=Ichiro Katayama|first=Lingli Yang|date=2015|title=4-(4-Hydroroxyphenyl)-2-butanol (rhododendrol) activates the autophagy-lysosome pathway in melanocytes: Insights into the mechanisms of rhododendrol-induced leukoderma|url=https://doi.org/10.1016/j.jdermsci.2015.01.006|journal=Journal of Dermatological Science|volume=77|issue=3|pages=182-185|doi=10.1016/j.jdermsci.2015.01.006|issn=0923-1811|via=Elsevier}} 5. ^1 {{Cite journal|last=Tokura|first=Yoshiki|last2=Fujiyama|first2=Toshiharu|last3=Ikeya|first3=Shigeki|last4=Tatsuno|first4=Kazuki|last5=Aoshima|first5=Masahiro|last6=Kasuya|first6=Akira|last7=Ito|first7=Taisuke|date=March 2015|title=Biochemical, cytological, and immunological mechanisms of rhododendrol-induced leukoderma|url=http://dx.doi.org/10.1016/j.jdermsci.2015.02.001|journal=Journal of Dermatological Science|volume=77|issue=3|pages=146–149|doi=10.1016/j.jdermsci.2015.02.001|issn=0923-1811}} 6. ^{{Cite journal|last=Kasamatsu|first=Shinya|last2=Hachiya|first2=Akira|last3=Nakamura|first3=Shun|last4=Yasuda|first4=Yuka|last5=Fujimori|first5=Taketoshi|last6=Takano|first6=Kei|last7=Moriwaki|first7=Shigeru|last8=Hase|first8=Tadashi|last9=Suzuki|first9=Tamio|date=October 2014|title=Depigmentation caused by application of the active brightening material, rhododendrol, is related to tyrosinase activity at a certain threshold|url=http://dx.doi.org/10.1016/j.jdermsci.2014.07.001|journal=Journal of Dermatological Science|volume=76|issue=1|pages=16–24|doi=10.1016/j.jdermsci.2014.07.001|issn=0923-1811}} 7. ^1 {{Cite journal|last=Sasaki|first=Minoru|last2=Kondo|first2=Masatoshi|last3=Sato|first3=Kohji|last4=Umeda|first4=Mai|last5=Kawabata|first5=Keigo|last6=Takahashi|first6=Yoshito|last7=Suzuki|first7=Tamio|last8=Matsunaga|first8=Kayoko|last9=Inoue|first9=Shintaro|date=2014-06-26|title=Rhododendrol, a depigmentation-inducing phenolic compound, exerts melanocyte cytotoxicity via a tyrosinase-dependent mechanism|url=http://dx.doi.org/10.1111/pcmr.12269|journal=Pigment Cell & Melanoma Research|volume=27|issue=5|pages=754–763|doi=10.1111/pcmr.12269|issn=1755-1471}} 8. ^{{Cite journal|last=Yang|first=Lingli|last2=Yang|first2=Fei|last3=Wataya-Kaneda|first3=Mari|last4=Tanemura|first4=Atsuhi|last5=Tsuruta|first5=Daisuke|last6=Katayama|first6=Ichiro|date=March 2015|title=4-(4-Hydroroxyphenyl)-2-butanol (rhododendrol) activates the autophagy-lysosome pathway in melanocytes: Insights into the mechanisms of rhododendrol-induced leukoderma|url=http://dx.doi.org/10.1016/j.jdermsci.2015.01.006|journal=Journal of Dermatological Science|volume=77|issue=3|pages=182–185|doi=10.1016/j.jdermsci.2015.01.006|issn=0923-1811}} 1 : Chemical compounds |
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