Effects of Hochu‐ekki‐to and Ninjin‐youei‐to, Traditional Japanese Medicines, on Porcine Serum‐Induced Liver Fibrosis in Rats

Abstract

In this study, we estimated the effects of traditional Japanese medicines on liver fibrosis in Wistar rats injected with porcine serum twice a week for 8 weeks. The rats were orally administered Hochu‐ekki‐to, Ninjin‐youei‐to (100 and 300 mg/kg/day) or Sho‐saiko‐to (300 mg/kg/day) 5 days per week. Serum and liver samples were obtained 2 days after the last porcine serum injection. Hochu‐ekki‐to and Ninjin‐youei‐to showed significant suppressive effects on the increase in hepatic hydroxyproline, namely total collagen. Further, Ninjin‐youei‐to significantly suppressed the increases of type IV collagen localized in the basement membrane and prolyl 4‐hydroxylase, a collagen synthesis enzyme, in serum or liver. Hochu‐ekki‐to showed a similar trend. Although Sho‐saiko‐to did not significantly suppress the increase in hepatic hydroxyproline, it intensely suppressed serum type IV collagen. Further, Hochu‐ekki‐to, Ninjin‐youei‐to, and Sho‐saiko‐to inhibited the production of fibrogenic cytokines, namely TGF‐β1 and IL‐13, in the serum and liver. Additionally, we showed that IL‐13 levels were positively correlated with hydroxyproline contents in the liver. These results suggest that Ninjin‐youei‐to as well as Hochu‐ekki‐to suppress porcine serum‐induced liver fibrosis more effectively than Sho‐saiko‐to. The effects of these three medicines probably depend on the inhibition of fibrogenic cytokine production, resulting in the suppression of collagen synthesis and deposition in the liver, though different mechanisms underlie their anti‐fibrogenic effects.