36062-05-2 六氢姜黄素

危险性质：非危险化学品

• 姜黄素代谢物 六氢姜黄素是姜黄素在上消化道发生还原反应生成的主要代谢产物，属于姜黄色素类物质。姜黄素的这种还原性代谢反应广泛发生在肠细胞和肝细胞中。不同的还原酶在其底物中引入反应基团和极性基团，产生活性代谢物，即二氢姜黄素、四氢姜黄素(DHC)、六氢姜黄素(THC)和八氢姜黄素(Octahydrocurcumin)。 姜黄素及其还原产物可在UDP葡糖醛酸转移酶的作用下，形成姜黄素葡糖醛酸结合物。部分姜黄素在人苯酚磺基转移酶同工酶(SULF1A1和SULF1A3)的催化下，形成姜黄素的磺酸盐，即磺酸姜黄素，其与姜黄素相比生物活性较低。Holder等人报道，在大鼠体内姜黄素的主要代谢产物是四氢、六氢姜黄素的葡糖醛酸结合物，胆汁代谢物是少量的二氢阿魏酸和微量的阿魏酸。 健康受试者单次口服10g或12g姜黄素的药代动力学研究发现，约4h后血浆中检测到姜黄素葡糖醛酸和磺酸结合物。通常口服给药后，在1至2小时内观察到姜黄素峰值血液浓度，并在大约12小时后变得检测不到。
• 生物活性 Hexahydrocurcumin 是姜黄素的主要代谢产物之一，是一种选择性的口服活性 COX-2 抑制剂，对 COX-1 无活性。Hexahydrocurcumin 具有抗氧化，抗癌和抗炎的作用。
• 靶点 COX-2
• 体外研究 Hexahydrocurcumin (0-25 μM; 24-48 hours; HT-29 cells) treatment significantly decreased the viability of HT-29 colon cancer cells in a time- and concentration-dependent. The respective IC 50 values for 24 and 48 h of Hexahydrocurcumin exposureare 77.05 and 56.95, respectively. Hexahydrocurcumin (0-25 μM; 24-48 hours; HT-29 cells) combined with 5-fluorouracil (5-FU; 5 µM) markedly reduces the COX-2 expression. The level of COX-1 is not altered. Hexahydrocurcumin (0-25 μM; 24-48 hours; HT-29 cells) combined with 5-fluorouracil (5-FU; 5 µM) markedly reduces the COX-2 protein. The level of COX-1 protein is not altered. Hexahydrocurcumin (7-14 μM; 24 hours) attenuates lipopolysaccharide (LPS)-elicited increase of prostaglandin E 2 (PGE 2 ) in murine macrophages (RAW 264.7) in a concentration-dependent manner. Cell Viability Assay Cell Line: HT-29 cells Concentration: 0 µM, 5 µM, 10 µM, 25 µM Incubation Time: 24 hours or 48 hours Result: Significantly decreased the viability of HT-29 colon cancer cells. RT-PCR Cell Line: HT-29 cells Concentration: 25 µM Incubation Time: 24 hours Result: Combined with 5-fluorouracil (5-FU; 5 µM) markedly reduced the COX-2 expression. Western Blot Analysis Cell Line: HT-29 cells Concentration: 25 µM Incubation Time: 24 hours Result: Combined with 5-fluorouracil (5-FU; 5 µM) markedly reduced the COX-2 protein.
• 体内研究 Hexahydrocurcumin (50 mg/kg; oral administration; daily; for 16 weeks; male Wistar rats) treatment significantly reduces the numbers of aberrant crypt foci (ACF) in colon cancer rats. Hexahydrocurcumin also markedly decreases COX-2 protein expression. The levels of COX-1 protein is not different from normal rats. Animal Model: Male Wistar rats (100-120 g) injected with dimethylhydrazine (DMH) Dosage: 50 mg/kg Administration: Oral administration; daily; for 16 weeks Result: Significantly reduced the numbers of ACF in colon cancer rats. Also markedly decreased COX-2 protein expression.
• 六氢姜黄素，姜黄色素（curcuminoid）类物质的一种，来源于姜科植物姜黄根茎或者姜根茎一种化学成分。具有利胆作用。

医药

姜黄素还原合成法

• 步骤: 姜黄素在肠细胞和肝细胞中经还原酶作用，引入反应基团和极性基团，生成六氢姜黄素（THC）；或通过姜黄素与还原剂（如氢气）在催化剂作用下发生还原反应，生成六氢姜黄素。
• 条件: 还原反应在肠细胞、肝细胞或实验室条件下进行，实验室中可能使用特定还原酶或化学还原剂（如硼氢化钠等），在适宜温度和pH条件下反应。
• 收率: 未明确提及具体收率数据。