Taraxasterol from dandelion improves glycolipid metabolism dysfunction in diet-induced metabolic dysfunction-associated steatotic liver disease by modulating hepatic FXR.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE: Dandelion (also known as Taraxaci Herba), a plant used in traditional Chinese medicine for both medicinal and dietary purposes, serves as a key ingredient in various liver-protecting herbal formulations. Its primary bioactive compound, taraxasterol (TAR), exhibits antioxidant and anti-inflammatory properties and can inhibit lipid synthesis. Nevertheless, the specific mechanism underlying its role in metabolic dysfunction-associated steatotic liver disease (MASLD) remains unclear. MATERIALS AND METHODS: The study integrated ethnopharmacological knowledge with modern techniques. Following in vitro assessment of lipid clearance in mouse hepatocytes, network pharmacology analysis was performed to identify potential targets. The therapeutic effects of TAR were subsequently validated in a high-fat diet-induced MASLD mouse model, with a focus on the FXR signaling pathway. RESULTS: TAR effectively reduced hepatic lipid accumulation and inflammation, confirming its ethnopharmacological relevance. Network analysis revealed that TAR's multi-target effects converge on the FXR signaling pathway. In vivo experiments demonstrated that TAR significantly alleviated HFD-induced metabolic dysregulation and liver injury through FXR activation, with efficacy abolished upon FXR knockdown. CONCLUSION: TAR ameliorates HFD-induced MASLD by modulating and enhancing the expression of hepatic FXR, thereby normalizing glucolipid metabolism and restraining oxidative and inflammatory damage. These findings position TAR as a promising plant-derived candidate for MASLD therapy and provide mechanistic insight into its hepatoprotective action.