Ono M, Miyamura M, Kyotani S, Saibara T, Ohnishi S, Nishioka Y
Department of Pharmacy, Kochi Medical School Hospital, Nankoku, Japan.
J Pharm Pharmacol. 2000 Jan;52(1):111-8. doi: 10.1211/0022357001773599.
To examine the effects of Sho-saiko-to extract on liver regeneration, Sho-saiko-to extract (0.75%, 1.5% or 3%) was administered to 70% partial hepatectomized rats with dimethylnitrosamine-induced liver-injury. S phase cell number, liver retinoid levels, hepatocyte growth factor (HGF) and transforming growth factor-beta (TGF-beta) levels in each intraorgan were measured as indicators of liver regeneration. Three to seven days after hepatectomy, HGF and TGF-beta levels of the liver and spleen of the Sho-saiko-to extract groups were significantly different from the levels of the ordinary food group (P < 0.05-0.1). HGF levels in the Sho-saiko-to extract groups were approximately 1.3-1.8 times higher in the liver and approximately 1.8-2.1 times higher in the spleen compared with the levels found in the ordinary food group. TGF-beta levels in the Sho-saiko-to extract groups were approximately 0.38-0.47 times the level in the liver and 0.58-0.77 times the level in the spleen of the ordinary food group. There was no difference in HGF and TGF-beta levels of the kidney and lung between the Sho-saiko-to extract group and the ordinary food group. There was a significant and positive correlation between HGF level and S phase cell number in the liver (r = 0.826, P < 0.01). There was a significant and negative correlation between TGF-beta level and the retinoid level in the liver (r = -0.696, P < 0.01). In addition, the levels of the active constituents of Sho-saiko-to extract (glycyrrhetic acid, baicalin and baicalein) showed high values in the liver and spleen of partial hepatectomized rats, and increased from the third day after partial hepatectomy. These results show that Sho-saiko-to extract induces liver regeneration by increasing the production of HGF and suppressing the production of TGF-beta in the liver and spleen of partial hepatectomized rats. It was considered that the increase in the Sho-saiko-to extract active constituent levels in the liver and spleen greatly influences this action.
为研究小柴胡汤提取物对肝再生的影响,将小柴胡汤提取物(0.75%、1.5%或3%)给予经二甲基亚硝胺诱导肝损伤的70%部分肝切除大鼠。测量各器官内的S期细胞数、肝脏类维生素A水平、肝细胞生长因子(HGF)和转化生长因子-β(TGF-β)水平,作为肝再生的指标。肝切除后3至7天,小柴胡汤提取物组肝脏和脾脏的HGF和TGF-β水平与普通饲料组相比有显著差异(P<0.05 - 0.1)。与普通饲料组相比,小柴胡汤提取物组肝脏中的HGF水平约高1.3 - 1.8倍,脾脏中的HGF水平约高1.8 - 2.1倍。小柴胡汤提取物组肝脏中的TGF-β水平约为普通饲料组肝脏水平的0.38 - 0.47倍,脾脏中的TGF-β水平约为普通饲料组脾脏水平的0.58 - 0.77倍。小柴胡汤提取物组与普通饲料组肾脏和肺的HGF和TGF-β水平无差异。肝脏中HGF水平与S期细胞数之间存在显著正相关(r = 0.826,P<0.01)。肝脏中TGF-β水平与类维生素A水平之间存在显著负相关(r = -0.696,P<0.01)。此外,小柴胡汤提取物的活性成分(甘草次酸、黄芩苷和黄芩素)水平在部分肝切除大鼠的肝脏和脾脏中较高,且在部分肝切除后第三天开始升高。这些结果表明,小柴胡汤提取物通过增加部分肝切除大鼠肝脏和脾脏中HGF的产生并抑制TGF-β的产生来诱导肝再生。认为肝脏和脾脏中小柴胡汤提取物活性成分水平的升高对这一作用有很大影响。