麝香酮对姜黄素在大鼠体内药动学及脑分布的影响

Effect of muscone on the pharmacokinetic and brain distribution of curcumin in rat

建立大鼠脑组织及血浆中姜黄素及四氢姜黄素的HPLC-MS/MS检测方法,并研究麝香酮对姜黄素大鼠体内药动学及脑分布的影响.将大鼠分为姜黄素组(10 mg/kg),姜黄素与麝香酮低、高剂量(0. 8 mg/kg、1. 6 mg/kg)联合组.利用HPLC-MS/MS检测SD大鼠尾静脉注射药物后,姜黄素及代谢物四氢姜黄素在血浆和脑组织中的浓度变化,计算药动学参数.姜黄素组与香酮低剂量联合姜黄素组比较,姜黄素血浆中的药时曲线曲线下面积AUC_(0-∞)分别为(18 026. 34±3 221. 75)(μg/L)·min和(23 205. 28±2 030. 73)(μg/L)·min,血浆药物总清除率CL_z分别为(0. 57±0. 09) L/(min·kg)和(0. 43±0. 04) L/(min·kg);在脑组织中,姜黄素组与香酮低剂量联合姜黄素组比较,姜黄素的AUC_(0-t)分别为(1 508. 82±616. 03)(μg/L)·min和(200. 18±70. 87)(μg/L)·min,四氢姜黄素的AUC_(0-t)分别为(893. 33±378. 63)(μg/L)·min和(181. 39±95. 00)(μg/L)·min.结果显示,低剂量的麝香酮可以促进姜黄素在体内的吸收,并减慢姜黄素在体内的清除,但是对于姜黄素脑组织分布并没有促进作用.

To develop a HPLC-MS/MS method for the determination of curcumin and tetrahydrocurcumin in rat plasma and brain tissue and to study the effect of muscone on the pharmacokinetic and brain distribution of curcumin in rat.The rats were divided into curcumin group(10 mg/kg)and curcumin combined with muscone group.After intravenous injection,HPLC-MS/MS was used to detect the concentration of curcumin and tetrahydrocurcumin in plasma and brain tissue,and calculate the pharmacokinetic parameters.The curcumin group was compared with urcumin combined with muscone group.The AUC(0-∞)of the curcumin in plasma were(18 026.34±3 221.75)(μg/L)·min and(23 205.28±2 030.73)(μg/L)·min respectively,the CL z were(0.57±0.09)L/(min·kg)and(0.43±0.04)L/(min·kg)respectively,the AUC(0-t)of the curcumin in brain tissue were(1 508.82±616.03)(μg/L)·min and(200.18±70.87)(μg/L)·min respectively,the AUC(0-t)of the tetrahydrocurcumin in brain tissue were(1 508.82±616.03)(μg/L)·min and(200.18±70.87)(μg/L)·min respectively.The results indicated that low-dose of muscone can significantly accelerate the absorption and slow down the drug clearance of curcumin in rat in vivo.However,the muscone did not promote the distribution of curcumin in brain tissue.