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Astragaloside IV (AS-IV) is one of the major bio-active ingredients of huang qi which is the dried root of Astragalus membranaceus (a traditional Chinese medicinal plant). The pharmacological effects of AS-IV, including anti-oxidative, anti-cancer, and anti-diabetic effects have been actively studied, however, the effects of AS-IV on liver regeneration have not yet been fully described. Thus, the aim of this study was to explore the effects of AS-IV on regenerating liver after 70% partial hepatectomy (PHx) in rats. Differentially expressed mRNAs, proliferative marker and growth factors were analyzed. AS-IV (10 mg/kg) was administrated orally 2 h before surgery. We found 20 core genes showed effects of AS-IV, many of which were involved with functions related to DNA replication during cell division. AS-IV down-regulates MAPK signaling, PI3/Akt signaling, and cell cycle pathway. Hepatocyte growth factor (HGF) and cyclin D1 expression were also decreased by AS-IV administration. Transforming growth factor β1 (TGFβ1, growth regulation signal) was slightly increased. In short, AS-IV down-regulated proliferative signals and genes related to DNA replication. In conclusion, AS-IV showed anti-proliferative activity in regenerating liver tissue after 70% PHx.

Polydeoxyribonucleotide (PDRN) is an agonist of the A2A adenosine receptors. We evaluated the effects of PDRN on liver regeneration induced by partial hepatectomy (PH) in rats, focusing on cell proliferation. Proliferating cell nuclear antigen (PCNA) as an indicator of cell proliferation was targeted to determine whether PDRN treatment could promote proliferation of hepatic cells in regenerating liver. Male Sprague-Dawley rats were divided into three groups: normal group (n= 3) without PH (sham operated), control groups (n= 12) with saline injection after PH, and experimental groups (n= 12) with i.p. injection of 8 mg/kg of PDRN immediately after PH. Light microscopically, liver regeneration induced by PH involved proliferation of various hepatic cells including parenchymal cells and Kupffer cells. The disintegration (1 or 2 days after PH) and remodeling (4 days after PH) of hepatic plate and increase of sinusoids (6 days after PH) were sequentially observed. These regenerative processes occurred relatively earlier in the experimental groups. By western blotting, the expression of PCNA increased in the early stage, reached its peak at 1 and 2 days after PH, and decreased thereafter. By immunohistochemistry, the intensities of PCNA staining in the experimental groups were more obvious at various days after PH. By electron microscopy using immunogold labeling for PCNA, the gold particles were largely observed in heterochromatin and nucleolus in hepatic cells. The results of immunochemistry and western blotting for PCNA showed the similar pattern in most groups. These findings suggest that PDRN treatment to hepatectomized rat could accelerate liver regeneration through rapid cell proliferation. [ABSTRACT FROM PUBLISHER]

Liver regeneration is a process involving highly organized and ordered tissue growth triggered by the loss of liver tissue. This process has remained a fascinating topic in medicine. In this study, we examined the effects of recombinant human interleukin-2 (rhIL-2) in rats under cirrhotic conditions. Thirty rats were divided into three groups, and liver cirrhosis was induced by injecting diethylnitrosamine for 2 weeks and CCl4for 8 weeks. After induction of cirrhosis, rhIL-2 was injected daily into their tail vein for three days and then hepatocyte growth factor (HGF), immunocytes in the blood, and TNF-αproduction were analyzed. The analysis showed that TNF-αwas significantly downregulated in the liver without significant changes in nitric oxide and caspase-3/7 activities in primary cultured liver cells. In terms of the number of immunocytes, there were no significant differences between the control and the treated groups. However, HGF levels were significantly higher in the treated groups than the control (saline administration) group. Treatment of rhIL-2 significantly increased the proliferation of primary cultured liver cells. The proliferation rates of primary cultured liver cells were correlated with the upregulation of HGF by treatment with rhIL-2in vivoandin vitro.These results suggest that rhIL-2 affects liver regeneration, which is at least related to the upregulation of HGF under cirrhotic conditions in rats. [ABSTRACT FROM AUTHOR]