Cholestasis is a complex hepatobiliary syndrome without effective treatment. Agrimonia pilosa Ledeb has been used in traditional Chinese medicine for centuries to treat various diseases, including inflammatory diseases, liver and gallbladder disorders. The active ingredient of agrimonolide (AM) is a derivative of the isocoumarin from Agrimonia pilosa Ledeb. In this study, we evaluated the pharmacological effect of AM and its mechanism for the treatment of cholestatic liver injury. To explore the pharmacological effects and mechanisms of AM in chronic cholestatic liver injury, we conducted two independent experiments. In the first study, DDC-induced cholestasis liver injury mice were treated with three doses of AM (10, 30, and 90 mg/kg), which resulted in dose-dependent alleviation of ductular proliferation, intraductal plugs, pericholangitis, fibrosis, and macrophage infiltration. Specifically, the antifibrotic and anti-inflammatory effects of AM were evidenced by increased bile acid efflux and export. In the second study, a high dose of 90 mg/kg AM was used to confirm its hepatoprotective pharmacological effects against cholestatic liver injury. Mechanistically, bile acid efflux and the transporter inhibitor BMS-986020 diminished the AM-mediated hepatoprotective effect because co-treatment resulted in diminishing three main effects of AM: suppression of ductular proliferation, biliary fibrosis, and macrophage infiltration.. AM has therapeutic potential in cholestatic liver diseases by ameliorating ductular proliferation, fibrosis, and macrophage infiltration through the inhibition of bile acid excretion transporters.
Han et al. (Fri,) studied this question.