A Triterpenoid-Enriched GLE70 Fraction From Ganoderma lingzhi Ameliorates Alcoholic Liver Disease via Multi-Target...

Alcoholic liver disease (ALD) arises from chronic alcohol consumption and progresses toward severe hepatic injury. Ganoderma lingzhi (G. lingzhi) triterpenoids possess notable hepatoprotective potential, yet the dense structure and complex chemical composition of the fruiting body make it challenging to obtain representative and bioactive fractions. In this study, an ultrasound-assisted enzymatic extraction was used to prepare a Ganoderma lingzhi triterpenoid-enriched extract (GLE), and its hepatoprotective effects were evaluated through physicochemical characterization, network pharmacology, and animal experiments. The optimized extraction yielded 16.32 ± 0.22 mg of total triterpenoids per gram of dry material. Functional screening identified GLE70 as the most active fraction, showing strong antioxidant activity, alcohol dehydrogenase activation, inhibition of carbohydrate-hydrolysing enzymes, and bile acid binding capacity. HPLC-TOF-MS/MS analysis showed that GLE70 contained multiple triterpenoids, with eight relatively abundant components including ganoderic acids B and D. Network pharmacology and molecular docking predicted AKT1, TNF, and SRC as key targets associated with the hepatoprotective effects of GLE70. In vivo, GLE70 increased AKT1 expression, reduced TNF-α and SRC-associated inflammatory signals, and improved hepatic function, antioxidant status, and lipid metabolism, suggesting a coordinated multi-target regulatory effect. Overall, this study obtained a bioactive triterpenoid-enriched fraction from G. lingzhi and provided insights into its multi-target regulatory characteristics in alleviating ALD, providing a basis for further application of G. lingzhi triterpenoids in liver protection.