Takeda S, Arai I, Hasegawa M, Tatsugi A, Aburada M, Hosoya E
Tsumura Research Institute for Pharmacology, Ibaraki, Japan.
Nihon Yakurigaku Zasshi. 1988 Apr;91(4):237-44. doi: 10.1254/fpj.91.237.
TJN-101 [+)-(6S, 7S, R-biar)-5,6,7,8-tetrahydro-1,2,3,12-tetramethoxy- 6,7-dimethyl-10,11-methylenedioxy-6-dibenzo [a, c] cyclooctenol) is one of the lignan compounds isolated from Schisandra fruits. When TJN-101 was administered orally at the doses of 3-100 mg/kg/day for 4 days, bile secretion, hepatic excretion of dye or hepatic hemodynamics 24 hr after the last dose was investigated in comparison with the phenobarbital (100 mg/kg/day)-treated group. Bile flow was dose-dependently increased; in contrast, biliary concentration of bile acids was decreased in TJN-101 (30 and 100 mg/kg/day)-treated groups. Similar changes were also observed in the phenobarbital-treated group. These results suggested that the enhancement of bile secretion caused by TJN-101 or phenobarbital was due to an increase of a bile acid-independent fraction. In the bromosulfophthalein (BSP) clearance test for liver function, both TJN-101 (30 and 100 mg/kg/day) and phenobarbital accelerated the disappearance from the blood and biliary excretion of BSP. Hepatic hemodynamics was examined by the hydrogen clearance method and measurement of liver wet and dry weight. Liver blood flow tended to increase in the TJN-101 (10-100 mg/kg/day) or phenobarbital-treated group. On the other hand, TJN-101 (3-100 mg/kg/day) or phenobarbital hardly altered the water content of the liver. These results suggested that the liver enlargement caused by both compounds was not accompanied with hepatic edema and that the enhancement of bile secretion or hepatic excretion of BSP might be related to an increase of liver blood flow.
TJN - 101 [+(6S, 7S, R - biar) - 5,6,7,8 - 四氢 - 1,2,3,12 - 四甲氧基 - 6,7 - 二甲基 - 10,11 - 亚甲基二氧基 - 6 - 二苯并[a, c]环辛烯醇]是从五味子果实中分离出的木脂素类化合物之一。当TJN - 101以3 - 100毫克/千克/天的剂量口服给药4天时,与苯巴比妥(100毫克/千克/天)治疗组相比,在最后一剂给药24小时后研究胆汁分泌、染料的肝脏排泄或肝脏血流动力学。胆汁流量呈剂量依赖性增加;相反,TJN - 101(30和100毫克/千克/天)治疗组胆汁酸的胆汁浓度降低。在苯巴比妥治疗组中也观察到类似变化。这些结果表明,TJN - 101或苯巴比妥引起的胆汁分泌增强是由于胆汁酸非依赖部分增加所致。在用于肝功能的溴磺酞钠(BSP)清除试验中,TJN - 101(30和100毫克/千克/天)和苯巴比妥均加速了BSP从血液中的消失和胆汁排泄。通过氢清除法以及测量肝脏湿重和干重检查肝脏血流动力学。TJN - 101(10 - 100毫克/千克/天)或苯巴比妥治疗组肝脏血流量有增加趋势。另一方面,TJN - 101(3 - 100毫克/千克/天)或苯巴比妥几乎未改变肝脏的含水量。这些结果表明,两种化合物引起的肝脏肿大并未伴有肝水肿,并且胆汁分泌增强或BSP的肝脏排泄增加可能与肝脏血流量增加有关。