The Kampo medicine Daikenchuto (TU-100) prevents bacterial translocation and hepatic fibrosis in a rat model of biliary atresia

Background. Biliary atresia is the most common cause of end-stage liver disease in children. It is known that bile duct ligation contributes to liver fibrosis via bacterial translocation (BT) and toll-like receptor 4 (TLR4) signaling of hepatic stellate cells (HSCs). We have reported previously that the traditional Japanese medicine, Dai-kenchu-to (TU-100), a form of Kampo medicine prevents BT in rats exposed to the stress of fasting. The aim of this study was to clarify the effect of TU-100 on a rat model of biliary atresia using bile duct ligation. Methods. Bile duct ligation and subsequent daily oral administration of TU-100 was performed in 6 week-old rats. The rats were killed at 3, 7, or 14 days after bile duct ligation to evaluate the liver injury, occurrence of BT, and hepatic fibrosis. As an in vitro experiment, we isolated fresh HSCs from the rats undergoing bile duct ligation. After cell attachment, TU-100 and its 3 component herbs (eg, processed ginger, ginseng radix, and Japanese pepper) were added, and the expressions of Alpha actin2 (acta2), Alpha-1 type I collagen (colla1), and tissue inhibitor of metalloproteinase 1 (timp1) were analyzed. Results. In vivo experiments demonstrated that oral administration of TU-100 decreased liver injury and atrophy of intestinal mucosa BT, hepatic fibrosis, and hepatic expression of alpha smooth muscle actin (alpha SIVIA) and TLR4, compared with rats that underwent bile duct ligation only. In vitro experiments showed that administration of TU-100 or the component herbs inhibited the expressions of acta2, collal, and timp1 in the HSCs. Conclusion. TU-100 prevented BT, activation of HSCs, and subsequent hepatic fibrosis. TU-100 may prevent progression of hepatic fibrosis in children with biliary atresia and improve prognosis.