Persimmon leaf extract ameliorates hyperlipidemia by modulating lipid genes expression and gut microbiota in high-fat-diet-fed mice.

BACKGROUND

Hyperlipidemia is characterized by abnormally elevated blood lipids. Persimmon leaf has multiple pharmacological activities and is valued for its lipid-lowering effect. However, few reports have revealed the hypolipidemic mechanism of persimmon leaf. In this study, compositions from the ethanol extract of persimmon leaf (PLE) were identified by high-resolution liquid chromatography-electrospray ionization-tandem mass spectrometry and high-performance liquid chromatography. The mechanism of PLE against hyperlipidemia induced by high-fat diet in mice was then explored based on lipid gene expression and gut microbiota.

RESULTS

The study demonstrated that 27 compositions from PLE were identified, of which the primary hypolipidemic compositions were astragalin, hyperoside, catechin, chlorogenic acid, and quercetin. Supplementation of PLE could reduce serum lipids, liver injury, lipid accumulation, and inflammation. The analysis of lipid gene expression indicated that PLE downregulated the expression of lipid synthesis genes FAS (fatty acid synthase; P < 0.001), ACC (acetyl coenzyme A carboxylase; P < 0.01), SCD1 (stearyl coenzyme A dehydrogenase 1; P < 0.05) and SREBP-1c (sterol regulatory element binding protein 1c; P < 0.01), while upregulating the expression of lipid degradation genes PPAR-α (peroxide-activated receptor alpha; P < 0.05) and CYP7A1 (cholesterol 7α-hydroxylase; P < 0.05). Simultaneously, PLE greatly recovered the intestinal short-chain fatty acid content, especially butyric acid (P < 0.05), valeric acid (P < 0.01) and isovaleric acid (P < 0.05). Furthermore, 16S rRNA analysis showed that PLE decreased the Firmicutes/Bacteroidetes ratio and increased the abundance of Lactobacillus, Turicibacter, and Dubosiella microbiota, which maintained the homeostasis of intestinal flora.

CONCLUSION

PLE could prevent lipid metabolism disorders and modulate gut microbiota homeostasis in hyperlipidemic rats. This study provides insights into PLE as a natural active substance for the prevention of hyperlipidemia. © 2025 Society of Chemical Industry.