Yinchenhao decoction and its active compound rhein ameliorate intrahepatic cholestasis of pregnancy in mice via modulation of intestinal flora

Background: Intrahepatic cholestasis of pregnancy (ICP), a medical condition, increases the risk of adverse pregnancy outcomes. Since the causes and mechanisms behind ICP remain unclear, the available treatment options are presently restricted.

Purpose: This research sought to explore the therapeutic efficacy of Yinchenhao decoction (YCHD), a traditional Chinese medicine formula, using two different ICP mouse models, as well as to clarify its fundamental mechanisms of action.

Methods: Through HPLC-MS and network pharmacology, the active ingredients of YCHD for treating the two mouse models of ICP were studied. The therapeutic mechanisms of YCHD and its active ingredient rhein in the two mouse models of ICP were studied using 16S rRNA technology.

Results: The findings of this research indicated that the gut microbiota in individuals with ICP undergoes specific changes. Furthermore, mice that are given the intestinal microbiome from these patients can exhibit characteristics of the ICP phenotype. Notably, YCHD led to significant enhancements in the clinical features of mice modeled for ICP and partially restored the balance of their gut flora. Further experiments revealed that rhein is the key active ingredient of YCHD in ICP treatment. Rhein can significantly improve the clinical phenotypes of mice in two different ICP models and correct their imbalanced intestinal flora. In addition, interventions involving YCHD and rhein led to a decrease in g_Fimenecus abundance, while simultaneously increasing g_Intestimonas abundance, which may be the key mechanism by which YCHD and rhein affect ICP.

Conclusion: YCHD and rhein could have beneficial impacts on ICP mouse models through the modulation of gut microbiota, offering a novel approach to clinical ICP management.

Intestinal flora; Intrahepatic cholestasis of pregnancy; Rhein; Yinchenhao decoction.