AI Article Synopsis
- Cholestasis is a serious liver condition caused by bile acid accumulation, and Artemisia capillaris, known as Yinchen, has been historically used in China to treat it, yet its mechanisms remain unclear.
- The study aims to explore how Yinchen decoction (YCD) protects against liver damage caused by cholic acid through FXR signaling, using a mouse model for intrahepatic cholestasis.
- Results show that YCD significantly improves liver function and protects against injury by activating specific signaling pathways related to bile acid homeostasis, although this effect is lost in mice lacking the FXR receptor, identifying chlorogenic and caffeic acids as potential therapeutic components.
Article Abstract
Ethnopharmacological Relevance: Cholestasis is a pathophysiological syndrome characterized by the accumulation of bile acids (BAs) that leads to severe liver disease. Artemisia capillaris is documented in Chinese Pharmacopoeia as the authentic resources for Yinchen. Although Yinchen (Artemisia capillaris Thunb.) decoction (YCD) has been used in China for thousands of years to treat jaundice, the underlying mechanisms to ameliorate cholestatic liver injury have not been elucidated.
Aim Of The Study: To investigate the molecular mechanism of how YCD protects against 1% cholic acid (CA) diet-induced intrahepatic cholestasis through FXR signaling.
Materials And Methods: Wild-type and Fxr-deficient mice were fed a diet containing 1% CA to establish the intrahepatic cholestasis model. The mice received low-, medium-, or high-dose YCD for 10 days. Plasma biochemical markers were analyzed, liver injury was identified by histopathology, and hepatic and plasma BA content was analyzed. Western blot was used to determine the expression levels of transporters and enzymes involved in BA homeostasis in the liver and intestine.
Results: In wild-type mice, YCD significantly improved plasma transaminase levels, multifocal hepatocellular necrosis, and hepatic and plasma BA contents, upregulated the expression of hepatic FXR and downstream target enzymes and transporters. Meanwhile, YCD significantly induced the expressions of intestinal FXR and FGF15 and hepatic FGFR4. In contrast, the hepatic protective effect of YCD on cholestasis was abolished in Fxr-deficient mice.
Conclusion: YCD protects against cholestatic liver injury induced by a CA diet by restoring the homeostasis of BAs via activation of the liver FXR/SHP and ileal FXR/FGF15 signaling pathways. Furthermore, chlorogenic acid and caffeic acid may be the pharmacological agents in YCD responsible for protecting against cholestatic liver injury.
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| http://dx.doi.org/10.1016/j.jep.2023.116560 | DOI Listing |
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