Placenta extract promote liver regeneration in CCl4-injured liver rat model

Int Immunopharmacol. 2011 Aug;11(8):976-84. doi: 10.1016/j.intimp.2011.02.012. Epub 2011 Feb 24.

Abstract

The human placenta is an organ for fetus development and abundant reservoir of various bioactive molecules. Interest to human placenta extract (hPE) is growing, and application with trial of hPE is widening in oriental medicine including in liver diseases. However, underlying mechanisms for therapeutic effects are still unclear. Here, we investigated therapeutic effects of hPE in carbon tetrachloride (CCl(4))-injured rat liver model in vivo and in damaged rat hepatic cells exposed to CCl(4) in vitro. In addition, regulation of inflammatory responses by treatment of hPE was investigated. Serum levels of GOT/AST and GPT/ALT were significantly reduced (P<0.05), and uptake/excretion of indocyanine green in serum was significantly induced at 3 weeks after intravenous hPE administration in CCl(4)-injured rat model (P<0.05). Expression of type I collagen (Col I) and α-smooth muscle actin (α-SMA) was decreased, whereas that of matrix metalloproteinase-9 (MMP-9) was increased resulting in improvement of score for fibrotic grade in hPE group. Also, albumin, proliferation activities and molecules associated with liver regeneration (e.g. interleukin-6, gp130, ATP binding cassette transporters, cyclin A) were more increased in hPE administration group than Non-hPE group. hPE administration suppressed activated T-cell proliferation via increasing anti-inflammatory cytokines and decreasing pro-inflammatory cytokines. These results suggest that hPE could be effective for liver disease through reduction of fibrosis, induction of liver regeneration, and regulation of inflammatory responses. These findings are important for understanding the roles of hPE and provide evidences for therapeutic effects of hPE in hepatic diseases which could lead to potential clinical applications.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP-Binding Cassette Transporters / metabolism
  • Actins / antagonists & inhibitors
  • Actins / genetics
  • Albumins / metabolism
  • Alkyl and Aryl Transferases / blood
  • Animals
  • Carbon Tetrachloride / toxicity
  • Cell Proliferation / drug effects
  • Chemical and Drug Induced Liver Injury / drug therapy*
  • Chemical and Drug Induced Liver Injury / genetics
  • Chemical and Drug Induced Liver Injury / metabolism
  • Chemical and Drug Induced Liver Injury / pathology
  • Collagen Type I / antagonists & inhibitors
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Cyclin A / metabolism
  • Cytokines / metabolism
  • Female
  • Fibrosis / drug therapy
  • Hepatocytes / drug effects*
  • Hepatocytes / metabolism
  • Humans
  • Indocyanine Green / pharmacokinetics
  • Inflammation / drug therapy
  • Inflammation / metabolism
  • Liver / drug effects
  • Liver / metabolism
  • Liver Regeneration / drug effects*
  • Liver Regeneration / genetics
  • Male
  • Matrix Metalloproteinase 9 / genetics
  • Placental Extracts / chemistry
  • Placental Extracts / pharmacology*
  • Pregnancy
  • Rats
  • Rats, Sprague-Dawley
  • T-Lymphocytes / drug effects
  • Transferases (Other Substituted Phosphate Groups) / blood

Substances

  • ATP-Binding Cassette Transporters
  • Actins
  • Albumins
  • Collagen Type I
  • Cyclin A
  • Cytokines
  • Placental Extracts
  • smooth muscle actin, rat
  • Carbon Tetrachloride
  • Alkyl and Aryl Transferases
  • geranylpyrophosphate olivetolate geranyltransferase
  • Transferases (Other Substituted Phosphate Groups)
  • UDP-GlcNAc-undecaprenyl phosphate N-acetylglucosaminyl 1-phosphate transferase
  • Matrix Metalloproteinase 9
  • Indocyanine Green