Study on the Mechanism of Guizhi Fuling Decoction in Treating Hyperlipidemia Based on Network Pharmacology and Experimental Methods
Mi Zhang1, Yuntian Zhang1, Hongyun Wang1, Chunlei Fan1★★ Corresponding author
- 1School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, CHINA.
CORRESPONDENCE
Chunlei Fan
School of Life Sciences, Zhejiang Chinese Medical University, Hangzhou, Zhejiang, CHINA.
Received: 18-07-2024; Accepted: 21-08-2024.
Volume 21, Issue 1 · pp. 152–160 · PUBLISHED 2025 · DOI: 10.1177/09731296241281441
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ABSTRACT
Background: Hyperlipidemia, caused by abnormal lipid metabolism, has become a significant health concern, especially in younger populations. While statins are commonly used for treatment, they often cause severe side effects with long-term use, leading to increased interest in finding natural alternatives. Objectives: This study aimed to investigate how Guizhi Fuling Decoction (GZFL) treats hyperlipidemia using network pharmacology and experimental validation. Materials and Methods: Network pharmacology analyzed GZFL’s active components, targets, and treatment mechanisms for hyperlipidemia. Hyperlipidemia rat and high-fat cell models were established. Experimental validation included enzymelinked immunosorbent assay, Western blot, quantitative polymerase chain reaction, Oil Red O staining, and other methods. Statistical analysis was performed using one-way analysis of variance followed by Tukey’s post hoc test for multiple comparisons. Pearson correlation analysis was used to identify correlations between key protein expressions and lipid levels. Results: GZFL comprises 85 active components and targets 218 proteins. Hyperlipidemia involves 3,852 targets, with 175 overlapping targets. Key targets included estrogen receptor 1, prostaglandin-endoperoxide synthase 2, interleukin-6 (IL-6), protein kinase B (AKT) 1, tumor necrosis factor, interleukin-1 beta, peroxisome proliferator-activated receptor gamma (PPARG), tumor protein p53 (TP53), and fructo oligosaccharide (FOS). Major active components were quercetin, phytosterols, kaempferol, and baicalein. Enrichment analysis highlighted processes like lipopolysaccharide response and lipid signaling pathways. Animal studies showed GZFL significantly reduced serum total cholesterol, triglycerides, and low-density lipoprotein cholesterol levels, and increased apolipoprotein A1 (p < 0.05). Western blot indicated that GZFL influenced AKT, TP53, IL-6, PPARγ expression, and mRNA levels in the phosphatidylinositol 3-kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) pathway (p < 0.01). Serum pharmacology experiments demonstrated GZFL-medicated serum reduced lipid droplet formation in high-fat cell models. Conclusion: GZFL contains multiple pharmacologically active components, such as quercetin, phytosterols, and kaempferol, which can influence lipid metabolism. It may exert its effects by regulating proteins like AKT, TP53, IL-6, and PPARγ, participating in lipid and atherosclerosis signaling pathways and the PI3K/AKT/mTOR pathway.
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Zhang, M., Zhang, Y., Wang, H., & Fan, C. (2025). Study on the Mechanism of Guizhi Fuling Decoction in Treating Hyperlipidemia Based on Network Pharmacology and Experimental Methods. Pharmacognosy Magazine, 21(1), 152–160. https://doi.org/10.1177/09731296241281441