Puerarin improves MASLD by remodeling intestinal microenvironment to promote mitochondrial fusion and autophagy

Area of Science:

• Pharmacology
• Hepatology
• Microbiology

Background:

• Pueraria Mirifica exhibits anti-inflammatory and lipid-lowering effects.
• Puerarin is identified as a key active component.
• Non-alcoholic fatty liver disease (NAFLD), now termed Metabolic dysfunction-associated steatotic liver disease (MASLD), is a growing health concern.

Purpose of the Study:

• To investigate the therapeutic mechanisms of Pueraria and its active component, puerarin, in treating MASLD.
• To elucidate how puerarin modulates the gut microbiota and its impact on liver health.
• To explore the relationship between gut flora, short-chain fatty acids, and hepatic lipid metabolism.

Main Methods:

• Utilized a high-fat diet (HFD) mouse model to induce MASLD.
• Assessed therapeutic effects using serum and liver pathology indicators.
• Analyzed gut microbiota composition, short-chain fatty acid (SCFA) levels, and intestinal barrier integrity.
• Employed bioinformatics for microbial mechanism prediction and q-PCR for hepatic gene expression analysis.
• Conducted intestinal microbial clearance experiments for verification.

Main Results:

• Puerarin treatment reduced hepatic steatosis, inflammation, and vacuolar-like changes in HFD mice.
• Significant remodeling of gut microbiota abundance and diversity was observed.
• Increased SCFA content and improved intestinal mucosal barrier function were noted.
• Puerarin downregulated inflammatory cytokines and regulated hepatic lipid metabolism genes.
• Gut microbiota alterations and anti-inflammatory effects were confirmed as key mechanisms.

Conclusions:

• Puerarin demonstrates significant therapeutic potential for MASLD.
• The mechanism involves regulating gut microbiota, enhancing SCFA production, and reducing inflammation.
• Puerarin acts via the gut-liver axis to alleviate hepatic steatosis and metabolic dysfunction.