Chemical and Mechanistic Prediction Analysis of Anti-obesity Properties of Guang Hawthorn (Malus doumeri) Leaves...

This study aimed to characterize the bioactive compounds in Guang hawthorn (Malus doumeri) leaf extracts and evaluate their potential anti-obesity effects.

70% Ethanol and ethyl acetate extracts from M. doumeri leaves were administered to high-fat diet-induced obese rats. Serum levels of total cholesterol (TC), triglycerides (TG), highdensity lipoprotein (HDL-C), and low-density lipoprotein (LDL-C) were assessed. The chemical composition of the leaf extracts (HML) was analyzed using multi-chromatography, NMR, and mass spectrometry. Network pharmacology approaches were employed to explore the interactions between the identified compounds and obesity-related targets.

Rats receiving a high dose of the leaf extracts exhibited significantly lower TC, TG, and LDL-C levels compared to controls (p < 0.05), with a concurrent increase in HDL-C (p < 0.05). Three bioactive compounds-phlorizin, sieboldin, and kumatakenin β-7-O-glucoside-were identified in HML. Through database screening, 373 unique targets for these compounds and 8484 obesity-related targets were identified. Using R and Cytoscape software, 272 overlapping targets and 32 core targets were determined. Functional enrichment analysis revealed that the anti- obesity effects of HML were related to phosphorylation, cell proliferation, apoptosis, and kinase activities. Notably, the 32 core targets were implicated in cancer-related proteoglycans, progesterone- mediated oocyte maturation via FoxO, and the PI3K-Akt signaling pathway.

This research demonstrates the anti-obesity potential of sieboldin and kumatakenin β-7-O-glucoside in HML. These compounds, along with phlorizin, modulated the PI3K-Akt and FoxO signaling pathways and proteoglycan synthesis, contributing to the reversal of obesityrelated effects. These findings suggest that M. doumeri leaf extracts may offer a promising natural therapeutic approach for obesity management.