Page 61 - วารสารกรมการแพทย์แผนไทยฯ ปีที่ 10 ฉบับที่ 2 เสริม
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52 «“√ “√°“√·æ∑¬å·ºπ‰∑¬·≈–°“√·æ∑¬å∑“߇≈◊Õ° ªï∑’Ë 10 ©∫—∫∑’Ë 2 情¿“§¡- ‘ßÀ“§¡ (©∫—∫‡ √‘¡) 2555
PC-5
°“√»÷°…“°“√®”≈Õß‚¡‡≈°ÿ≈¢Õß “√ diarylheptanoids ®“°«à“π™—°¡¥≈Ÿ°
(Curcuma comosa) „π°“√ÕÕ°ƒ∑∏‘χªìπ phytoestrogen
1 2
≥—∞®π—π∑å ®ß°≈ , ª√– “π μ—È߬◊π¬ß«—≤π“
1
¿“§«‘™“«‘∑¬“»“ μ√åª√–¬ÿ°μå·≈– —ß§¡ «‘∑¬“≈—¬‡∑§‚π‚≈¬’Õÿμ “À°√√¡ ¡À“«‘∑¬“≈—¬‡∑§‚π‚≈¬’æ√–®Õ¡‡°≈â“
2
æ√–π§√‡Àπ◊Õ, §≥–°“√·æ∑¬å·ºπμ–«—πÕÕ° ¡À“«‘∑¬“≈—¬√—ß ‘μ
À≈—°°“√·≈–‡Àμÿº≈ «à“π™—°¡¥≈Ÿ° (Curcuma comosa Roxb.) «ß»å Zingiberaceae π‘¬¡„™â‡Àßâ“√—°…“Õ“°“√¢Õß
μ√’ ‡™àπª√–®”‡¥◊Õπ¡“‰¡àª°μ‘ ª«¥∑âÕß√–À«à“ß¡’ª√–®”‡¥◊Õπ μ°¢“« ¢—∫πÈ”§“«ª≈“ ´÷Ë߃∑∏‘Ï¥—ß°≈à“«‡™◊ËÕ«à“¡“®“° “√°≈ÿà¡
phytoestrogen „π°“√√“¬ß“π∑“ßæƒ°…‡§¡’·≈–°“√∑¥ Õ∫ƒ∑∏‘Ï∑“ß estrogenic activity ¢ÕßÕ¿‘™“μ ÿ¢ ”√“≠·≈–§≥–
“¡“√∂·¬° “√°≈ÿà¡ diarylheptanoids ∑’Ë¡’ƒ∑∏‘ÏμàÕ estrogen receptor (ERβ) ‰¥â„°≈⇧’¬ß°—∫ “√ 17β-Estradiol ß“π«‘®—¬
π’È π„®∑’Ë®–»÷°…“≈—°…≥–°“√®—∫μ—«√–À«à“ß “√ diarylheptanoids °—∫ estrogen receptor (ERβ) ·≈–‡ª√’¬∫‡∑’¬∫°“√®—∫
°—∫ 17β-Estradiol ‚¥¬„™â°“√®”≈Õß‚¡‡≈°ÿ≈ (molecular modeling) ¥â«¬‚ª√·°√¡ AutoDock Vina 1.1.2
«—μ∂ÿª√– ß§å »÷°…“°“√®—∫μ—«√–À«à“ß “√ diarylheptanoids °—∫ estrogen receptor (ERβ) ‚¥¬„™â°“√®”≈Õß‚¡‡≈°ÿ≈
¥â«¬‚ª√·°√¡ AutoDock Vina 1.1.2
«‘∏’¥”‡π‘π°“√ ¢âÕ¡Ÿ≈º≈¢Õß°“√°√–μÿâπ transcriptional activation ¢Õß “√°—∫ estrogen receptor (ERβ) ‰¥â®“°
Õ¿‘™“μ ÿ¢ ”√“≠·≈–§≥– (Bioorgnic & Medicinal Chemistry 16 (2008) 6891-6902) ‚§√ß √â“ß 3 ¡‘μ‘¢Õß “√∂Ÿ°
√â“ß·≈–§”≥«π√–¥—∫æ≈—ßß“πμË” ÿ¥¢Õß‚¡‡≈°ÿ≈‚¥¬„™â‚ª√·°√¡ GOLD (CCDC, UK) ‚§√ß √â“ß ERβ (2JYD) ‰¥â√—∫®“°
Brookhaven Protein Data Bank (www.rcsb.org) ≈—°…≥–¢Õß‚§√ß √â“ß·≈–ªØ‘ —¡æ—π∏å¢Õß “√°—∫ ERβ ®–∑”°“√®”≈Õß
∫π‚ª√·°√¡ AutoDock Vina 1.1.2 (http//autodock.scripp.edu/) §à“æ“√“¡‘‡μÕ√å„π°“√∑”ß“π¢Õß‚ª√·°√¡§◊Õ§à“ de-
fault °≈ÿà¡¢Õß “√∑’Ë¡’§à“ docking energy μË”∑’Ë ÿ¥®–∂Ÿ°‡≈◊Õ°¡“ 20 Õ—π¥—∫ ·≈–§à“ binding energy ®–∂Ÿ°∫—π∑÷°‰«â
º≈°“√»÷°…“ æ∫«à“À¡Ÿà phenolic ¢Õß “√À¡“¬‡≈¢ 15, 16 ¡’≈—°…≥–°“√®—∫°—∫ ERβ active site „πμ”·Àπà߇¥’¬«°—π
°—∫À¡Ÿà 3-hydroxy ¢Õß estradiol ‚¥¬¡’ binding energy ‡∑à“°—∫ -8.1 ·≈– -8.3 kcal/mol ‚¥¬ƒ∑∏‘Ï„π°“√°√–μÿâπ tran-
scriptional activation ¢Õß ERβ ¡’§à“‡∑à“°—∫ 90.56 ·≈– 87.75% μ“¡≈”¥—∫ ´÷ËßÀ¡Ÿà hydroxyl ®–‡°‘¥ hydrogen bonding
°—∫ Glu305 ·≈– Arg346 à«π phenyl ring Õ’°¥â“πÀπ÷Ëß®–®—∫°—∫ à«π∑’ˉ¡à¡’¢—È« (non-polar amino acid) ‰¥â·°à Ile373, Ile
376 ·≈– Leu380 à«π “√À¡“¬‡≈¢ 10 ∑’ˉ¡à¡’À¡Ÿà phenolic ®–¡’ binding energy ∑’ËμË”°«à“§◊Õ‡∑à“°—∫ -7.7 kcal/mol ·≈–
¡’ƒ∑∏‘Ï„π°“√°√–μÿâπ ERβ μË”°«à“ ‡™àπ°—π§◊Õ‡∑à“°—∫ 33.72%
¢âÕ √ÿª Diarylheptanoids ∑’Ë¡’À¡Ÿà phenolic ®–ÕÕ°ƒ∑∏‘Ï„π°“√°√–μÿâπ transcriptional activation ¢Õß ERβ ¥’
°«à“ “√∑’ˉ¡à¡’À¡Ÿà phenolic °“√»÷°…“°“√®—∫μ—«√–À«à“ß “√°—∫ receptor ‚¥¬„™â°“√®”≈Õß‚¡‡≈°ÿ≈¥â«¬‚ª√·°√¡ AutoDock
Vina 1.1.2 ‡ªìπ«‘∏’Àπ÷Ëß∑’˙૬Õ∏‘∫“¬°“√ÕÕ°ƒ∑∏‘Ï¢Õß “√„π ¡ÿπ‰æ√Õ¬à“߇ªìπ«‘∑¬“»“ μ√å ‡À¡“–°—∫°“√π”¡“ª√–¬ÿ°μå„™â„π
»÷°…“°“√ÕÕ°ƒ∑∏‘Ï¢Õß ¡ÿπ‰æ√‰∑¬