Protective effect of Maren-Tiaogan Decoction on high-fat diet-induced MASLD in mice

Recent epidemiological studies have highlighted a significant increase in the global prevalence of metabolic dysfunction-associated steatotic liver disease (MASLD). This study explores the hepatoprotective mechanisms of Maren-Tiaogan Decoction (MRTGD), a traditional Chinese medicine (TCM) formulation, using a high-fat diet (HFD) murine model of MASLD. The findings may provide a safer and more effective TCM-based therapeutic option for patients with MASLD.

A 12-week HFD-induced mouse model of MASLD was established. MRTGD was administered at high, medium and low doses via oral gavage twice daily as the therapeutic intervention. The chemical constituents of MRTGD were identified using UPLC-MS/MS. Hepatic steatosis and changes in adipocyte area were assessed using hematoxylin and eosin (H&E) staining and Oil Red O staining. Biochemical analyses were conducted to measure serum aminotransferase levels, serum lipid profiles, hepatic lipid content and oxidative stress. Furthermore, mRNA expression and protein abundance of critical regulators governing lipid homeostasis and autophagic flux were quantitatively analyzed through real-time reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot.

MRTGD, containing 467 constituents, exhibits significant protective effects against HFD-induced MASLD/MASH by suppressing elevated serum transaminases and hyperlipidemia, reducing hepatic lipid accumulation and steatosis, ameliorating histopathological alterations and adipocyte hypertrophy, while alleviating hepatocyte apoptosis and hepatic oxidative stress. MRTGD not only effectively restores the abnormal up-regulation of lipogenic proteins (such as SREBP-1c and ACC) and the down-regulation of lipid-catabolizing proteins (including PPARα), but also normalizes the expression levels of the PI3K/AKT/mTOR signaling pathway.

The experimental results demonstrate that MRTGD effectively prevents HFD-induced MASLD, partially through modulation of lipid metabolism and autophagy pathways.