"Dose-Effect-Response" Relationships of Paeoniae Radix Rubra on Alpha-Naphthylisothiocyanate-Induced Acute Cholestatic Hepatitis in Rats

Objective To investigate the hepatoprotective effects of Paeoniae Radix Rubra (PRR) at different doses against alpha-naphthylisothiocyanate (ANIT)-induced acute cholestatic hepatitis in rats. Methods Rats were ig admini- strated with vehicle or PRR ((1, 9, 18, 36, 54, 72, and 81 g/(kg·d)) 3 d before and 2 d after ANIT (60 mg/kg) ig administration. The general status of rats, histopathology of liver, serum alanine aminotransaminase, aspartate aminotransaminase, total bilirubin, direct bilirubin, and alkaline phosphatase levels, were observed at respective time points (24 and 48 h) after ANIT administration. Using cluster analysis and correspondence analysis, the "dose-effect-response" relationships of PRR were evaluated. Results The results showed that compared with model group, the serum biochemistry index significantly decreased with the increasing of PRR dosage (P < 0.01), and the change and necrosis of hepatic cellula, and inflammatory cell infiltration were gradually alleviated. However, the improvement was not obviously found in the low-dose group (1 g/(kg·d)). The cluster analysis and correspondence analysis results showed that different doses of PRR could significantly ameliorate ANIT-induced acute cholestatic hepatitis of rats in a dose-dependent manner. Conclusion The experiments show that administration doses of PRR in clinical use should be added properly in order to gain the expectant therapeutic effect, especially in the treatment of heavy acute cholestasis hepatitis.