Puerarin ameliorates metabolic dysfunction-associated fatty liver disease by inhibiting ferroptosis and inflammation

Area of Science:

• Biochemistry
• Pharmacology
• Hepatology

Background:

• Metabolic dysfunction-associated fatty liver disease (MAFLD) often co-occurs with type 2 diabetes mellitus (T2DM), worsening both conditions.
• Currently, no standardized treatments exist for MAFLD, highlighting the need for novel therapeutic strategies.

Purpose of the Study:

• To investigate the therapeutic potential of puerarin, a flavonoid, in ameliorating MAFLD.
• To elucidate the underlying mechanisms by which puerarin exerts its protective effects against MAFLD.

Main Methods:

• A MAFLD animal model was established using a high-fat diet (HFD) and streptozotocin (STZ).
• Palmitic acid (PA)-induced AML12 cells were used for in vitro studies.
• Puerarin treatment was administered to both models.
• Key molecular pathways, including SIRT1/Nrf2 signaling, ferroptosis, oxidative stress, and inflammation, were analyzed using techniques like Western blot and transmission electron microscopy.

Main Results:

• Puerarin administration improved glucose tolerance, insulin sensitivity, liver function, and lipid profiles in MAFLD mice.
• Puerarin significantly reduced oxidative stress and hepatic inflammation.
• Inhibition of ferroptosis was observed in vivo following puerarin treatment.
• Mechanistic studies revealed that puerarin upregulates SIRT1, enhances Nrf2 nuclear translocation, and its protective effects on AML12 cells were dependent on SIRT1 and Nrf2 activity.

Conclusions:

• Puerarin demonstrates significant therapeutic effects in ameliorating MAFLD.
• The mechanism involves the suppression of ferroptosis and inflammation via the SIRT1/Nrf2 signaling pathway.
• Puerarin holds promise as a potential therapeutic agent for managing MAFLD.