Effect of Sho-saiko-to Extract on HGF and TGF-β Levels of Intraorgans in Liver-injured Rats after Partial Hepatectomy

Abstract

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.

Transforming Growth Factor-β1 Released from the Spleen Exerts a Growth Inhibitory Effect on Liver Regeneration in Rats

“…They also concluded that splenic TGF-␤1 produced growth inhibitory effect on the cirrhotic liver, and we concur with them that a similar mechanism may have taken place during liver regeneration following PH. Similarly, it was shown that Sho-saiko-to extract (glycyrrhetic acid, baicalin, and baicalein) caused enhanced liver regeneration by inhibiting the production of TGF-␤1 in the spleen in 70% partially hepatectomized rats with dimethylnitosamineinduced liver-injury model (Ono et al, 2000). This further proves our hypothesis that the spleen contributes a major inhibitory role in liver regeneration by producing and releasing TGF-␤1.…”

Effects of Extract Derived from <i>Eriobotrya japonica</i> on Liver Function Improvement in Rats

“…Although many studies have evaluated methods of inhibiting the development of liver fibrosis, no adequate means has yet been found. [18][19][20][21] Based on the pharmacological background of Eriobotrya japonica, various extracts of the seeds were orally administered to rats with dimethylnitrosamine-induced hepatopathy. Subsequently, blood L-asparate aminotransferase (AST) and L-alanine aminotransferase (ALT) levels, liver retinoid (an index of fibroblast expression in the liver) level, and hydroxyproline (a collagen-specific amino acid) level were measured.…”

Effect of Sho-saiko-to Extract on Hepatic Inflammation and Fibrosis in Dimethylnitrosamine Induced Liver Injury Rats.

“…3) In this time, we prepared model rats with various stages of liver injury by administering several dosages of DMN for different duration, to clarify the relationship between the stage of liver injury and effectiveness of Sho-saiko-to. We have already discussed the effects of various concentrations of extract (0.75, 1.5, 3.0%) on hepatopathy in rats in previous reports.…”

“…We have already discussed the effects of various concentrations of extract (0.75, 1.5, 3.0%) on hepatopathy in rats in previous reports. 1,3) According to the results of these previous experiments, we decided on the Sho-saiko-to extract concentration of 1.5%, which was administered in the present study. We have also carried out previous studies comparing the effects of Sho-saiko-to extract with glycyrrhizin, baicalin and baicalein, respectively.…”

“…Extraction and Measurement of TGF-b b in the Liver Liver TGF-b was extracted by the method described in the previous study, 3) and measured using a multiplate spectrophotometer (Ultramark, Nihon Biorad, Japan) at a wavelength of 450 nm (reference, 570 nm).…”