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<p>According to gas chromatography-mass spectrometry (GC-MS) analysis, mulberry seed oil (MSO) contains a high proportion of unsaturated fatty acids, accounting for 88.26% of its total composition. Although unsaturated fatty acids are reported to have lipid-lowering activity, the molecular targets involved in the mechanism of lipid-lowering action of MSO have not yet been systematically demonstrated. This mechanism is explored through an interdisciplinary approach, employing network pharmacology and molecular docking analysis techniques, supplemented by in vivo experimental validation. We employ network pharmacology to identify candidate targets, assessed binding affinity through molecular docking, and conducted experimental validation in LO2 cells and <i>C. elegans</i> to evaluate lipid-lowering activity. Network pharmacology identified 157 shared targets between MSO and obesity, subsequently pinpointing IL-6 and PPARG as core targets through protein-protein interaction analysis. The active components of MSO were found to bind with these targets with high binding affinities by molecular docking. The results demonstrated that MSO alleviates lipid accumulation in oleic acid-induced LO2 cell model, reduces lowering total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), whilst simultaneously elevating high-density lipoprotein cholesterol (HDL-C) levels. Furthermore, Western blot analysis showed that MSO dose-dependently suppressed p-RAF, MEK, ERK, and BCL-2 expression, implicating the RAF/MEK/ERK pathway in MSO-mediated lipid regulation. In <i>C. elegans</i>, MSO lowered triglyceride and cholesterol levels and modulated the insulin/IGF-1 signaling pathway. A systemic explanation of the multi-target regulatory process of MSO over lipid metabolism is described in our findings, which is the scientific basis of its development.</p>

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Lipid-lowering activity of mulberry seed unsaturated fatty acids: integrating network pharmacology and experimental validation

  • 期刊论文

  • 发表日期：

    2026年6月17日

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  • Yue Zhang,
  • Haoran Huang,
  • Jianglong He,
  • Yuqi Li,
  • Xueping Jiang,
  • Ping Wu,
  • Syed Asim Shah Bacha,
  • Ran Zhang,
  • Hao Li,
  • Gaiqun Huang,
  • Zhongzheng Gui

摘要

According to gas chromatography-mass spectrometry (GC-MS) analysis, mulberry seed oil (MSO) contains a high proportion of unsaturated fatty acids, accounting for 88.26% of its total composition. Although unsaturated fatty acids are reported to have lipid-lowering activity, the molecular targets involved in the mechanism of lipid-lowering action of MSO have not yet been systematically demonstrated. This mechanism is explored through an interdisciplinary approach, employing network pharmacology and molecular docking analysis techniques, supplemented by in vivo experimental validation. We employ network pharmacology to identify candidate targets, assessed binding affinity through molecular docking, and conducted experimental validation in LO2 cells and C. elegans to evaluate lipid-lowering activity. Network pharmacology identified 157 shared targets between MSO and obesity, subsequently pinpointing IL-6 and PPARG as core targets through protein-protein interaction analysis. The active components of MSO were found to bind with these targets with high binding affinities by molecular docking. The results demonstrated that MSO alleviates lipid accumulation in oleic acid-induced LO2 cell model, reduces lowering total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), whilst simultaneously elevating high-density lipoprotein cholesterol (HDL-C) levels. Furthermore, Western blot analysis showed that MSO dose-dependently suppressed p-RAF, MEK, ERK, and BCL-2 expression, implicating the RAF/MEK/ERK pathway in MSO-mediated lipid regulation. In C. elegans, MSO lowered triglyceride and cholesterol levels and modulated the insulin/IGF-1 signaling pathway. A systemic explanation of the multi-target regulatory process of MSO over lipid metabolism is described in our findings, which is the scientific basis of its development.