Potential inhibitory effect of Shigyakusan on gallstone formation in a mice model of cholesterol gallstone Disease

Cholesterol gallstones (CGs) are formed in the biliary system due to cholesterol supersaturation in the bile and delayed bile excretion. The current treatments for CGs involve potentially severe complications, and novel therapeutic approaches are still required. Shigyakusan is a traditional Chinese medicine used for treating CG disease (CGD), but there are no reports on the action or efficacy of Shigyakusan in CGD. The present study was conducted to clarify the inhibitive effects of Shigyakusan on CGD. Mice were fed a normal or lithogenic diet for 8 weeks (to create a mouse model of CGD) and simultaneously treated with vehicle or Shigyakusan. Organs were removed after blood sampling to examine CG formation and perform pathological evaluations. Genetic analysis of the liver, gallbladder, and ileum tissues was also conducted. CGD was induced by feeding mice with a lithogenic diet. Specifically, gallstones were detected, and serum T-CHO and LDL-C were significantly elevated. Administration of Shigyakusan to CGD mice reduced the development of CGs and lowered the serum T-CHO and LDL-C levels. Additionally, Shigyakusan administration increased ABCG5/G8 and ABCB4 mRNA expression in the liver, AQP5 expression in the gallbladder, and ABCG5 expression in the ileum of CGD mice. Shigyakusan administration diminished the synthesis of CGs in mice by lowering serum cholesterol and improving bile flow. The results show that Shigyakusan may be a beneficial option for CGD treatment and prevention.