Hepatoprotective effects of Hovenia dulcis seeds against alcoholic liver injury and related mechanisms investigated via network pharmacology

Background: Alcoholic liver disease (ALD) is a worldwide health problem, and natural products have been shown to improve ALD due to their antioxidant activities. Some parts of Hovenia dulcis (H. dulcis), such as roots, peduncles, and stems, provide health benefits. Nevertheless, the effects and mechanisms of H. dulcis seeds on ALD have not yet been fully elucidated.

Aim: To determine H. dulcis antioxidant activity, evaluate its effects against ALD, and investigate the related mechanisms via network pharmacology.

Methods: The antioxidant activity of H. dulcis seed was determined by both ferric-reducing antioxidant power and trolox equivalent antioxidant capacity assays. The total phenolic and flavonoid contents were determined by Folin-Ciocalteu method and aluminum chloride colorimetry, respectively, and polysaccharide was determined by phenol-sulfuric acid method. The effects of H. dulcis seeds against alcoholic liver injury were investigated in mice with water extract pretreatment for 7 days followed by alcohol administration. Moreover, the mechanisms of action were explored with network pharmacology.

Results: The results showed that H. dulcis seeds possessed strong antioxidant activity (245.11 ± 10.17 μmol Fe²⁺/g by ferric-reducing antioxidant power and 284.35 ± 23.57 μmol TE/g by trolox equivalent antioxidant capacity) and contained remarkable phenols and flavonoids, as well as a few polysaccharides. H. dulcis seeds attenuated alcohol-induced oxidative liver injury, showing reduced serum alanine and aspartate aminotransferases, alkaline phosphatase, and triglyceride, elevated hepatic glutathione, increased activities of superoxide dismutase and catalase, and reduced malondialdehyde and hepatic triglyceride. The results of network pharmacology analysis indicated that kaempferol, stigmasterol, and naringenin were the main bioactive compounds in H. dulcis seeds and that modulation of oxidative stress, inflammation, gut-derived products, and apoptosis were underlying mechanisms of the protective effects of H. dulcis seeds on ALD.

Conclusion: The results of this study demonstrate that H. dulcis seeds could be a good natural antioxidant source with protective effects on oxidative diseases such as ALD.

Keywords: Hovenia dulcis; Alcoholic liver disease; Antioxidant activity; Hepatoprotection; Network pharmacology; Oxidative stress.