Lu Chen, Guibing Meng, Yu Pan, Lijun Yin, Yu Liu, Danna Huang, Li Jiang, Ming-Sheng Lan, Chao Luo, Wuwei Wu
{"title":"Chemical and Mechanistic Prediction Analysis of Anti-obesity Properties of Guang Hawthorn (Malus doumeri) Leaves using Network Analysis.","authors":"Lu Chen, Guibing Meng, Yu Pan, Lijun Yin, Yu Liu, Danna Huang, Li Jiang, Ming-Sheng Lan, Chao Luo, Wuwei Wu","doi":"10.2174/0113862073375434250529170324","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>This study aimed to characterize the bioactive compounds in Guang hawthorn (Malus doumeri) leaf extracts and evaluate their potential anti-obesity effects.</p><p><strong>Methods: </strong>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.</p><p><strong>Results: </strong>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.</p><p><strong>Conclusion: </strong>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.</p>","PeriodicalId":10491,"journal":{"name":"Combinatorial chemistry & high throughput screening","volume":" ","pages":""},"PeriodicalIF":1.6000,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Combinatorial chemistry & high throughput screening","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2174/0113862073375434250529170324","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMICAL RESEARCH METHODS","Score":null,"Total":0}
引用次数: 0
Abstract
Objective: This study aimed to characterize the bioactive compounds in Guang hawthorn (Malus doumeri) leaf extracts and evaluate their potential anti-obesity effects.
Methods: 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.
Results: 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.
Conclusion: 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.
目的：研究广山楂叶提取物的生物活性成分，并评价其潜在的抗肥胖作用。方法：采用70%乙醇和乙酸乙酯提取物灌胃高脂饮食诱导的肥胖大鼠。评估血清总胆固醇（TC）、甘油三酯（TG）、高密度脂蛋白（HDL-C）和低密度脂蛋白（LDL-C）水平。采用多层色谱、核磁共振、质谱等方法对叶提取物（HML）进行化学成分分析。采用网络药理学方法来探索鉴定的化合物与肥胖相关靶点之间的相互作用。结果：与对照组相比，大鼠接受高剂量的叶提取物显示出显著降低的TC、TG和LDL-C水平（p < 0.05），同时HDL-C升高（p < 0.05）。在HML中鉴定出3种生物活性化合物：根连素、木犀草素和熊竹素β-7- o -葡萄糖苷。通过数据库筛选，鉴定出这些化合物的373个独特靶点和8484个肥胖相关靶点。利用R和Cytoscape软件，确定了272个重叠靶点和32个核心靶点。功能富集分析表明，HML的抗肥胖作用与磷酸化、细胞增殖、凋亡和激酶活性有关。值得注意的是，这32个核心靶点与癌症相关的蛋白聚糖、孕酮介导的卵细胞成熟（通过FoxO）和PI3K-Akt信号通路有关。结论：本研究证实了西叶酚素和熊竹素β-7- o -葡萄糖苷在HML中的抗肥胖作用。这些化合物与苯丙素一起调节PI3K-Akt和FoxO信号通路和蛋白聚糖合成，有助于逆转肥胖相关的影响。这些发现表明，杜梅叶提取物可能为肥胖管理提供了一种很有前途的天然治疗方法。
期刊介绍：
Combinatorial Chemistry & High Throughput Screening (CCHTS) publishes full length original research articles and reviews/mini-reviews dealing with various topics related to chemical biology (High Throughput Screening, Combinatorial Chemistry, Chemoinformatics, Laboratory Automation and Compound management) in advancing drug discovery research. Original research articles and reviews in the following areas are of special interest to the readers of this journal:
Target identification and validation
Assay design, development, miniaturization and comparison
High throughput/high content/in silico screening and associated technologies
Label-free detection technologies and applications
Stem cell technologies
Biomarkers
ADMET/PK/PD methodologies and screening
Probe discovery and development, hit to lead optimization
Combinatorial chemistry (e.g. small molecules, peptide, nucleic acid or phage display libraries)
Chemical library design and chemical diversity
Chemo/bio-informatics, data mining
Compound management
Pharmacognosy
Natural Products Research (Chemistry, Biology and Pharmacology of Natural Products)
Natural Product Analytical Studies
Bipharmaceutical studies of Natural products
Drug repurposing
Data management and statistical analysis
Laboratory automation, robotics, microfluidics, signal detection technologies
Current & Future Institutional Research Profile
Technology transfer, legal and licensing issues
Patents.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
