Application of widely targeted metabolomics combined with network pharmacology and molecular docking to elucidate growth stage-specific metabolite accumulation and predict the diuretic mechanisms of Leontopodium leontopodioides (Willd.) Beauv
- 1College of Grassland Science, Key Laboratory of Forage Cultivation, Processing and High Efficient Utilization of Ministry of Agriculture and Rural Affairs, Key Laboratory of Grassland Resources, Ministry of Education, Inner Mongolia Agricultural University
- 2Inner Mongolia Academy of Agricultural and Animal Husbandry Sciences
Abstract
Leontopodium leontopodioides (Wild.) Beauv. (LLB) was investigated to determine its metabolite profiles and bioactivities across different growth stages. Ultrasound-assisted extraction was employed to obtain total flavonoids and phenolic acids from LLB samples collected at the vegetative and reproductive stages, and their in vitro antioxidant capacities were then evaluated. UHPLC-MS/MS-based metabolomics was subsequently used to compare the metabolite changes between the two growth stages. Finally, network pharmacology analysis was conducted to predict potential diuretic components and elucidate their mechanisms of action. The results revealed that samples from the vegetative stage contained higher levels of bioactive compounds and exhibited stronger antioxidant activity than those from the reproductive stage. A total of 1,817 metabolites were identified, belonging to 12 compound classes such as flavonoids, phenolic acids, lipids, amino acids and derivatives, and terpenoids. Comparative analysis revealed 305 differentially expressed metabolites between growth stages, predominantly flavonoids. KEGG pathway enrichment analysis showed significant enrichment of these differential metabolites in three biosynthetic pathways: flavone and flavonol biosynthesis, flavonoid biosynthesis, and isoflavonoid biosynthesis. Through integrated ingredient screening and network pharmacology, five potential diuretic components in Leontopodium leontopodioides (Wild.) Beauv were predicted: 3,4-dimethoxycinnamic acid, jasmonic acid, chrysin, rivularin, and tangeretin. Molecular docking validation suggested that these compounds likely exert diuretic effects by targeting key proteins such as AKT1, MAPK1, and MAPK3. Collectively, this work systematically elucidates the metabolic variations in Leontopodium leontopodioides (Wild.) Beauv. during different growth stages, predicts its diuretic potential from a multi-component, multi-target perspective, and reveals the underlying material basis and molecular mechanisms. These findings provide critical evidence for active compound screening and mechanistic clarification, supporting the future development of Leontopodium leontopodioides (Wild.) Beauv. into standardized diuretic agents or functional products with well-defined mechanisms of action.
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BibTeX
@article{yi2026application,
title = {{Application of widely targeted metabolomics combined with network pharmacology and molecular docking to elucidate growth stage-specific metabolite accumulation and predict the diuretic mechanisms of Leontopodium leontopodioides (Willd.) Beauv}},
author = {Rule Yi and Junfeng Hao and Zhijun Wang and Jian Bao and Zhuna Bao and Yuqi Zou and Mingga Qi and Yi Zhang and Gentu Ge},
journal = {Scientific Reports},
year = {2026},
month = jul,
doi = {10.1038/s41598-026-60647-y},
url = {https://doi.org/10.1038/s41598-026-60647-y},
note = {CC BY},
}
RIS
TY - JOUR
TI - Application of widely targeted metabolomics combined with network pharmacology and molecular docking to elucidate growth stage-specific metabolite accumulation and predict the diuretic mechanisms of Leontopodium leontopodioides (Willd.) Beauv
AU - Rule Yi
AU - Junfeng Hao
AU - Zhijun Wang
AU - Jian Bao
AU - Zhuna Bao
AU - Yuqi Zou
AU - Mingga Qi
AU - Yi Zhang
AU - Gentu Ge
PY - 2026
DA - 2026/07/01
JO - Scientific Reports
DO - 10.1038/s41598-026-60647-y
UR - https://doi.org/10.1038/s41598-026-60647-y
AB - Leontopodium leontopodioides (Wild.) Beauv. (LLB) was investigated to determine its metabolite profiles and bioactivities across different growth stages. Ultrasound-assisted extraction was employed to obtain total flavonoids and phenolic acids from LLB samples collected at the vegetative and reproductive stages, and their in vitro antioxidant capacities were then evaluated. UHPLC-MS/MS-based metabolomics was subsequently used to compare the metabolite changes between the two growth stages. Finally, network pharmacology analysis was conducted to predict potential diuretic components and elucidate their mechanisms of action. The results revealed that samples from the vegetative stage contained higher levels of bioactive compounds and exhibited stronger antioxidant activity than those from the reproductive stage. A total of 1,817 metabolites were identified, belonging to 12 compound classes such as flavonoids, phenolic acids, lipids, amino acids and derivatives, and terpenoids. Comparative analysis revealed 305 differentially expressed metabolites between growth stages, predominantly flavonoids. KEGG pathway enrichment analysis showed significant enrichment of these differential metabolites in three biosynthetic pathways: flavone and flavonol biosynthesis, flavonoid biosynthesis, and isoflavonoid biosynthesis. Through integrated ingredient screening and network pharmacology, five potential diuretic components in Leontopodium leontopodioides (Wild.) Beauv were predicted: 3,4-dimethoxycinnamic acid, jasmonic acid, chrysin, rivularin, and tangeretin. Molecular docking validation suggested that these compounds likely exert diuretic effects by targeting key proteins such as AKT1, MAPK1, and MAPK3. Collectively, this work systematically elucidates the metabolic variations in Leontopodium leontopodioides (Wild.) Beauv. during different growth stages, predicts its diuretic potential from a multi-component, multi-target perspective, and reveals the underlying material basis and molecular mechanisms. These findings provide critical evidence for active compound screening and mechanistic clarification, supporting the future development of Leontopodium leontopodioides (Wild.) Beauv. into standardized diuretic agents or functional products with well-defined mechanisms of action.
SN - 2045-2322
ER -