PROTECTIVE EFFECT OF PAEONIFLORIN ON IMMUNOLOGICAL LIVER INJURY INDUCED BY BACILLUS CALMETTE‐GUERIN PLUS LIPOPOLYSACCHARIDE: MODULATION OF TUMOUR NECROSIS FACTOR‐α AND INTERLEUKIN‐6 mRNA

Abstract

1. Paeoniflorin is one of the main effective components of the total glucosides of paeony (TGP) extracted from the root of Paeonia lactiflora which has been used for gynaecological problems and for cramp, pain and giddiness for over 1,500 years in Chinese medicine. Anti-inflammatory, antioxidative, antihepatic injury and immunoregulatory activities of TGP have been extensively proved in our laboratory for many years. Our present study investigates the effects and mechanisms of paeoniflorin on immunological liver injury in mice. 2. A model of immunological liver injury was induced by tail vein injection of bacillus Calmette-Guérin (BCG) and lipopolysaccharide (LPS) in mice. Activities of serum alanine aminotransferase (ALT) were measured by biochemical methods. Hepatic tissue sections were stained with haematoxylin and eosin and examined under a light microscope. Tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, lipopolysaccharide binding protein (LBP) and CD14 mRNA (messenger ribonucleic acid) expression in mouse liver were determined by semiquantitative reverse transcription polymerase chain reaction (RT-PCR) analysis. 3. Immunological liver injury induced by BCG plus LPS was successfully duplicated. Serum ALT activities were significantly decreased by paeoniflorin. (25, 50, 100 mg/kg). Histological examination demonstrated that paeoniflorin could attenuate the area and extent of necrosis and reduce the immigration of inflammatory cells. The increase in TNF-alpha, LBP and CD14 mRNA expression in mouse liver after BCG and LPS injection was significantly decreased by paeoniflorin (100 mg/kg) and was changed by paeoniflorin (25, 50 mg/kg) at different time-point. The augmentation of IL-6 mRNA in mouse liver was markedly increased by paeoniflorin at 1 h and 3 h after LPS injection. 4. Paeoniflorin could significantly protect against immunological liver injury in mice. TNF-alpha, IL-6, LBP and CD14 mRNA expression in mouse liver may be involved in BCG plus LPS induced liver injury. The protective mechanism of paeoniflorin might be partially related to modulation of TNF-alpha, IL-6, LBP and CD14 mRNA expressions in mouse liver.