The citrus shield: how quzhou fructus aurantii conquers MASH via PPARα activation

Metabolic dysfunction-associated steatohepatitis (MASH) is a progressive liver disease that often leads to cirrhosis and hepatocellular carcinoma. With current FDA-approved drugs facing limitations, natural alternative therapies are crucial. Quzhou Fructus Aurantii ethyl acetate extract (QFAEE), rich in diverse flavonoids, presents a compelling candidate for MASH treatment.

Evaluated in high-fat diet mice and palmitic acid-treated hepatocytes, QFAEE significantly ameliorated liver enlargement, lipid accumulation, and liver injury. It also displayed potent anti-inflammatory and anti-fibrotic effects, suppressing the NF-κB pathway, reducing proinflammatory cytokines, and restoring apoptotic balance.

Mechanistically, combining network pharmacology and RNA sequencing pinpointed the PPAR signaling pathway as QFAEE’s primary target. QFAEE selectively activated PPARα and RXRα. This activation upregulated CPT1A to enhance fatty acid β-oxidation while concurrently downregulating lipogenic markers (FAS, SCD1, CD36). When this pathway was blocked using the PPARα antagonist NXT629, MASH worsened, but QFAEE successfully reversed this, proving its PPARα dependence. Furthermore, molecular docking identified narirutin and nobiletin as key PPARα agonists within the extract. Ultimately, QFAEE offers a promising, multi-target natural therapy to halt MASH progression.

The work entitled “Quzhou Fructus Aurantii extract alleviates metabolic dysfunction-associated steatohepatitis by activating the PPARα signaling pathway” was published on Chinese Journal of Natural Medicines (published on July 20, 2026).