Human Placenta Hydrolysate Promotes Liver Regeneration via Activation of the Cytokine/Growth Factor-Mediated Pathway and Anti-oxidative Effect

Liver regeneration is a very complex process and is regulated by several cytokines and growth factors. It is also known that liver transplantation and the regeneration process cause massive oxidative stress, which interferes with liver regeneration. The placenta is known to contain various physiologically active ingredients such as cytokines, growth factors, and amino acids. In particular, human placenta hydrolysate (hPH) has been found to contain many amino acids. Most of the growth factors found in the placenta are known to be closely related to liver regeneration. Therefore, in this study, we investigated whether hPH is effective in promoting liver regeneration in rats undergoing partial hepatectomy. We confirmed that cell proliferation was significantly increased in HepG2 and human primary cells. Hepatocyte proliferation was also promoted in partial hepatectomized rats by hPH treatment. hPH increased liver regeneration rate, double nucleic cell ratio, mitotic cell ratio, proliferating cell nuclear antigen (PCNA), and Ki-67 positive cells in vivo as well as interleukin (IL)-6, tumor necrosis factor alpha (TNF-α), and hepatocyte growth factor (HGF). Moreover, Kupffer cells secreting IL-6 and TNF-α were activated by hPH treatment. In addition, hPH reduced thiobarbituric acid reactive substances (TBARs) and significantly increased glutathione (GSH), glutathione peroxidase (GPx), and superoxide dismutase (SOD). Taken together, these results suggest that hPH promotes liver regeneration by activating cytokines and growth factors associated with liver regeneration and eliminating oxidative stress.