- 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。
