Yinchenhao decoction inhibits autophagy via the mTOR signaling pathway to ameliorate pregnancy outcomes in intrahepatic cholestasis of pregnancy

Background: Intrahepatic cholestasis of pregnancy (ICP) is linked to negative outcomes in pregnancy, potentially due to placental autophagy dysfunction. Yinchenhao decoction (YCHD) may improve ICP outcomes, the object of this study was to examine the impact of YCHD on autophagy in the placenta of ICP rats and elucidate the underlying mechanisms. Methods: The ICP rat model was induced with 17α-ethinyl estradiol and treated with intragastric YCHD. An ICP HTR-8/SVneo cell model was created using taurocholic acid and treated with YCHD drug-containing serum. The decoction's impact on ICP was evaluated using hematoxylin-eosin staining and serum biochemical markers. Assessment of cell viability was conducted by employing the CCK-8 assay. Immunohistochemistry and Western blotting analyzed autophagy markers LC3I and LC3II in placental tissues. Key proteins and genes related to the mTOR pathway were studied via Western blotting and quantitative real-time PCR. An electron microscope was used to observe an autolysosome. Results: The damage induced by TCA in HTR-8/SVneo cells was notably alleviated by YCHD, which resulted in an upregulation of mTOR mRNA expression, a counteraction of rapamycin's mTOR pathway inhibition, and a decrease in LC3 expression. It improved survival and birth weight in ICP rats, restored liver function, and reduced bile acid. Additionally, YCHD lessened liver and placenta damage and decreased placental thrombosis. It activated p-mTOR/mTOR and p-PI3K/PI3K in the ICP rat placenta while inhibiting LC3II/LC3I, indicating mTOR pathway activation and autophagy inhibition. Conclusion: YCHD alleviated symptoms and pathological damage in ICP rats and counteracted the damage induced by TCA. Its therapeutic mechanism involved activating the mTOR signaling pathway, thereby inhibiting aberrant placental autophagy. These findings hold significant importance in enhancing the clinical utility of YCHD.