Title
Tyrosinase Inhibitory Active Components Contained in
Bangladesh Medicinal Plants and Elucidation of the Inhibition
Mechanism( 内容と審査の要旨(Summary) )
Author(s)
Mohammad Nuruzzaman Masum
Report No.(Doctoral
Degree)
博士(農学) 甲第715号
Issue Date
2019-03-31
Type
博士論文
Version
ETD
URL
http://hdl.handle.net/20.500.12099/78472
※この資料の著作権は、各資料の著者・学協会・出版社等に帰属します。㹙㸰㸲㹛
Ặ ྡ㸦ᮏ㸦ᅜ㸧⡠㸧 Mohammad Nuruzzaman Masum
㸦ࣂࣥࢢࣛࢹࢩࣗேẸඹᅜ㸧 Ꮫ ࡢ ✀ 㢮 ༤ኈ㸦㎰Ꮫ㸧 Ꮫ グ ␒ ྕ ㎰༤⏥➨㸵㸯㸳ྕ Ꮫ ᤵ ᖺ ᭶ ᪥ ᖹᡂ㸱㸯ᖺ㸱᭶㸱㸯᪥ ◊ ✲ ⛉ ཬ ࡧ ᑓ ᨷ 㐃ྜ㎰Ꮫ◊✲⛉ ⏕≀㈨※⛉Ꮫᑓᨷ ◊✲ᣦᑟࢆཷࡅࡓᏛ ᒱ㜧Ꮫ
Ꮫ ㄽ ᩥ 㢟 ┠ Tyrosinase Inhibitory Active Components Contained in Bangladesh Medicinal Plants and Elucidation of the
Inhibition Mechanism 㸦ࣂࣥࢢࣛࢹࢩࣗࡢ⸆⏝᳜≀ྵࡲࢀࡿࢳࣟࢩࢼ࣮ࢮ㜼ᐖ άᛶᡂศ㜼ᐖᶵᵓࡢゎ᫂㸧 ᑂ ᰝ ጤ ဨ ᰝ ᒱ㜧Ꮫ ᩍᤵ ᑎ ᮏ ዲ 㑥 ᰝ ᒱ㜧Ꮫ ᩍ ᤵ ග Ọ ᚭ ᰝ 㟼ᒸᏛ ᩍ ᤵ Ἑ ྜ ┿ ࿃ ᰝ ᒱ㜧Ꮫ ຓ ᩍ ᒣ ෆ ᜏ ⏕
ㄽ ᩥ ࡢ ෆ ᐜ ࡢ せ ᪨
ᮏ◊✲ࡣࠊࣂࣥࢢࣛࢹࢩ࡛ࣗ᥇ྲྀࡋࡓ 7 ✀㢮ࡢ⸆⏝᳜≀ࡽࠊB16 ࣓ࣛࣀ࣮࣐⣽⬊ᑐࡋప ẘᛶ࡛ࠊࢳࣟࢩࢼ࣮ࢮ㜼ᐖ࠾ࡼࡧ࣓ࣛࢽࣥ⏕⏘ᢚไάᛶࢆ♧ࡍᢳฟ≀ࢆࢫࢡ࣮ࣜࢽࣥࢢࡋࠊࡑ ࡢάᛶᡂศࡢ༢㞳ᵓ㐀ゎᯒࡉࡽάᛶᡂศࡢ࣓ࣛࢽࣥ⏕⏘ᢚไᶵᵓࡘ࠸࡚ㄽࡌ࡚࠸ࡿࠋ 7 ✀ࡢ᳜≀୰ࠊPersicaria orientalisࡢ᰿ᢳฟ≀ࡢࡳࡀࢳࣟࢩࢼ࣮ࢮࣔࣀࣇ࢙ࣀ࣮ࣛࢮ࠾ࡼࡧ ࢪࣇ࢙ࣀ࣮ࣛࢮ㜼ᐖάᛶࢆ᭷ࡋࠊIC50 ࡣࡑࢀࡒࢀ 13 ࠾ࡼࡧ 17ȣg/ml ࡛࠶ࡗࡓࠋࡲࡓࠊ P.orientalis᰿ᢳฟ≀ࡢ50, 25 ࠾ࡼࡧ 12.5ȣg/ml ࡢฎ⌮⃰ᗘ࡛ B16 ⣽⬊ᑐࡋ࡚㧗࠸⣽⬊⏕ Ꮡ⋡ࢆ♧ࡋࡓࠋࡑࡇ࡛ࠊࢳࣟࢩࢼ࣮ࢮ㜼ᐖάᛶᡂศࡢ༢㞳ࢆヨࡳࡓࠋࡲࡎࠊP.orientalisࡢ᰿ࡽMeOH ࡛ᢳฟ≀ࢆᚓࡓᚋࠊn-࣊࢟ࢧࣥࠊEtOAcࠊ࠾ࡼࡧ EtOH ࡛ࡑࢀࡒࢀศ㓄ࡋࡓࠋEtOAc ࠾ࡼࡧEtOH ྍ⁐㒊ࡣࠊࡑࢀࡒࢀ 39 ࠾ࡼࡧ 22ȣg/ml ࡢ IC50࡛ࠊᢳฟ≀ࡋ࡚ࡣⰋዲ࡞ࢳࣟ ࢩࢼ࣮ࢮ㜼ᐖάᛶࢆ♧ࡋࡓࠋ᭷ຠᡂศࡣࠊEtOH ྍ⁐㒊ࢆࢩࣜ࢝ࢤࣝ࠾ࡼࡧ Sephadex LH-20 ࣒࢝ࣛࠊḟ࠸࡛C-18 ㏫┦ศྲྀ HPLC ࡼࡾ༢㞳ࡋࠊ1Dࠊ2D NMR ࠾ࡼࡧ MALD-TOFMS ศ ᯒࡽࣄࢻࣟࣆ࣌ࣟࢩࢻ((1)㸪ࣂࢽࢥࢩࢻ A((2)㸪ࣂࢽࢥࢩࢻ B((3)㸪ࣂࢽࢥࢩࢻ C((4)㸪ࣂࢽࢥࢩ ࢻE((5)㸪࢚࢟ࢯࢳࢩࣥ(6)㸪࢚ࣆ࢝ࢸ࢟ࣥ-3-o-࣮࢞ࣞࢺ(7),࢞ࣜࢵࢡ㓟(8)࠾ࡼࡧ 3,4-ࢪࣄࢻࣟ࢟ ࢩᏳᜥ㤶㓟(9)ྠᐃࡋࡓࠋࡑࡢ࠺ࡕ 5 ✀ࡣࣇ࢙ࢽࣝࣉࣟࣃࣀࢻࢫࢡ࣮ࣟࢫ࢚ࢫࢸࣝ(ྜ≀ 1 㹼5)࡛P.orientalisࡢ᰿ࡢせ࡞ḟ௦ㅰ⏘≀࡛࠶ࡗࡓࠋ༢㞳ࡉࢀࡓྜ≀1㹼5 ࡢࢳࣟࢩࢼ࣮ ࢮάᛶ㜼ᐖࢆホ౯ࡋࡓࡇࢁࠊ࠸ࡎࢀࡶⰋዲ࡞ࢳࣟࢩࢼ࣮ࢮࣔࣀࣇ࢙ࣀ࣮ࣛࢮ࠾ࡼࡧࢪࣇ࢙ࣀ ࣮ࣛࢮ㜼ᐖάᛶࢆ♧ࡋࡓࠋࣔࣀࣇ࢙ࣀ࣮ࣛࢮ㜼ᐖάᛶ࡛ࡣࠊྜ≀1 ࡀ᭱ࡶᙉ࠸㜼ᐖ(IC50 27.1
ȣM)ࢆ♧ࡋࠊࢳࣟࢩࢼ࣮ࢮ㜼ᐖࡋ࡚⢝ရ㓄ྜࡉࢀ࡚࠸ࡿࢥ࢘ࢪ㓟ࡰྠ➼ࡢ್ࢆ♧ ࡋࡓࠋࢪࣇ࢙ࣀ࣮ࣛࢮ㜼ᐖάᛶ࡛ࡣྜ≀4 ࡀຠᯝⓗ࡛ࠊࢥ࢘ࢪ㓟ࡢ⣙ 2 ಸࡢຠᯝࢆ♧ࡋࡓࠋ ḟྜ≀11㹼5 ࡢ࣓ࣛࢽࣥ⏕⏘ᢚไస⏝ࡘ࠸࡚ B16 ࣓ࣛࣀ࣮࣐⣽⬊࡛ホ౯ࡋࡓࠋྜ≀ 1 ࠾ࡼࡧ 4 ࡣࠊ㧗⃰ᗘ(50ȣM)᮲௳࠾࠸࡚ࡶప⣽⬊ẘᛶࢆ♧ࡋࡓࠋࡉࡽྛྜ≀ࡣ⃰ᗘ౫Ꮡ ⓗ࣓ࣛࢽࣥ⏕⏘ᢚไస⏝ࢆ♧ࡋࠊ≉ྜ≀3 ࡣࠊ50 ࠾ࡼࡧ 25ȣM ࠾࠸࡚ࠊ᭷ព㧗࠸ ⣽⬊እ࣓ࣛࢽࣥ㜼ᐖάᛶ⋡ࢆ♧ࡋࡓࠋ⨾ⓑࡋ࡚⢝ရ㓄ྜࡉࢀ࡚࠸ࡿࣝࣈࢳࣥࡣࠊ730 ȣM ࡛࣓ࣛࢽࣥྜᡂᑐࡋ࡚ 58%ࡢ㜼ᐖຠᯝࢆ♧ࡋࡓࡀࠊྜ≀ 1ࠊ3 ࠾ࡼࡧ 4 ࡣࠊ50ȣM ࠸࠺ẚ㍑ⓗప⃰ᗘ࠾࠸࡚ࡶⰋዲ࡞࣓ࣛࢽࣥ⏘⏕ᢚไຠᯝࢆ♧ࡋࡓࠋࡲࡓࠊᵓ㐀άᛶ┦㛵ࡢ⤖ ᯝࠊࢢࣝࢥ࣮ࢫ6 ࡢࣇ࢙ࣝࣟࣝᇶ࠾ࡼࡧ 2 ࡲࡓࡣ 3 ࢭࢳࣝᇶࢆ᭷ࡍࡿᵓ㐀ࡣࠊ⣽ ⬊ẘᛶࡢᘬࡁ㔠࡞ࡗ࡚࠸ࡿࡀ᫂☜࡞ࡗࡓࠋ ௨ୖࡢ⤖ᯝࡽࠊP.orientalisࡢ᰿ᢳฟ≀ࡣࠊࢳࣟࢩࢼ࣮ࢮ㜼ᐖ࠾ࡼࡧ࣓ࣛࢽࣥ⏕⏘ᢚไ ࡋ⏝࡛ࡁࡿ」ᩘࡢ᭷ᮃ࡞ྜ≀ࢆྵ᭷ࡍࡿࡀ♧ࡉࢀࠊᐇ⏝ᛶࡢ࠶ࡿኳ↛⨾ⓑࡢ㛤Ⓨࡀ ᮇᚅࡉࢀࡿࠋ
ᑂ ᰝ ⤖ ᯝ ࡢ せ ᪨
⏦ㄳ⪅Mohammad Nuruzzaman Masum ࡣ㸪7 ✀ࡢࣂࣥࢢࣛࢹࢩࣗ⏘⸆⏝᳜≀ࡢࢫࢡࣜ ࣮ࢽࣥࢢࡼࡾ3HUVLFDULDRULHQWDOLVࡢ᰿࢚࢟ࢫࡢࡳࡀ᭷ᮃ࡞ࢳࣟࢩࢼ࣮ࢮ㜼ᐖάᛶࢆ᭷ ࡋ㸪ࡑࡢάᛶᡂศࢆ᥈⣴ࡋࡓࡇࢁ㸪 ✀㢮ࡢྜ≀ࡢ༢㞳ྠᐃᡂຌࡋࡓࠋࡑࡢ୰࡛ࢫࢡࣟ ࣮ࢫSࢡ࣐ࣝ㓟 ศᏊࡀ⤖ྜࡋࡓ ✀ࡢࣂࢽࢥࢩࢻㄏᑟయࡀࢳࣟࢩࢼ࣮ࢮ㜼ᐖάᛶ࠾ࡼࡧ % ࣓ࣛࣀ࣮࣐⣽⬊ࡢ࣓ࣛࢽࣥ⏕⏘ࢆᢚไࡋࡓࠋࡋࡋ࡞ࡀࡽ㸪ࢢࣝࢥ࣮ࢫࡢ ࠶ࡿ࠸ࡣ ࡀࢭࢸ࣮ࢺ࠾ࡼࡧ ࡀࣇ࢙࣮ࣝࣞࢺ࡞ࡗࡓྜ≀ ,9 9 ࡣ࣓ࣛࣀ࣮࣐⣽⬊ᑐࡋ࡚ ᙉẘᛶࢆ♧ࡍ⤖ᯝ࡞ࡗࡓࠋᚋࡣᵓ㐀άᛶ┦㛵◊✲ࡀ㐍ࡳ㸪⮫ᗋᐇ㦂࡛ࡢຠᯝࡀㄆࡵࡽࢀࢀ ࡤ㸪ᐇ⏝ᛶࡢ࠶ࡿኳ↛⢝ᩱ⨾ⓑࡢ㛤Ⓨ⧅ࡀࡿࡇࡀᮇᚅࡉࢀࡿࠋ
1. Mohammad Nuruzzaman Masum, Siwattra Choodej, Kosei Yamauchi and Tohru Mitsunaga (2018) Isolation of Phenylpropanoid Sucrose Esters from the Roots of Persicaria orientalis and Their Potential as Inhibitors of Melanogenesis. Medicinal Chemistry Research (iin press).
2. Mohammad N. Masum, Kosei Yamauchi and Tohru Mitsunaga (2018) Tyrosinase Inhibitors from Natural and Synthetic Sources as Skin-lightening Agents. Reviews in Agricultural Science (iin press).
