Abstract
The pathogenesis of non‐alcoholic fatty liver disease (NAFLD) is still not fully understood, and currently, no effective pharmacotherapy is available. Nuclear receptors (NRs) are important biological participants in NAFLD that exhibit great therapeutic potential. Chaihu Shugan powder (CSP) is a traditional Chinese medicine (TCM) formula that has a wide therapeutic spectrum including NAFLD, but the effective components and functional mechanisms of CSP are unclear. We adopted a network pharmacology approach using multiple databases for Gene Ontology (GO) enrichment analysis and the molecular complex detection (MCODE) method for a protein‐protein interaction (PPI) analysis, and we used molecular docking method to screen the NR targets and determine the corresponding CSP components. The screening results were validated through a NAFLD rat model that was used to explain the possible relationship between CSP and NAFLD. Finally, we screened PPARγ, FXR, PPARα, RARα and PPARδ as target genes and quercetin, kaempferol, naringenin, isorhamnetin and nobiletin as target compounds. The five components were detected through high‐performance liquid chromatography‐mass spectrometry (HPLC‐MS), the results of which aligned with the docking experiments of PPARγ, PPARα and PPARδ. After CSP intervention, the NAFLD rat model showed ameliorated effects in terms of bodyweight, hepatic histopathology, and serum and liver lipids, and the mRNA levels of PPARγ, FXR, PPARα and RARα were significantly changed. The results from this study indicate that CSP exhibits healing effects in an NAFLD model and that the network pharmacology approach to screening NR targets and determining the corresponding CSP components is a practical strategy for explaining the mechanism by which CSP ameliorates NAFLD.
Highlights
| 5177 of the HFD group, the Nuclear receptors (NRs) in the Chaihu Shugan powder (CSP) group exhibited a similar trend to that of the normal control (NC) group, but there was no significant difference. These results indicated that PPARγ and RARα may have been down-regulated in the non-alcoholic fatty liver disease (NAFLD) or high-fat diet rat model, whereas farnesoid X-activated receptor (FXR), PPARα and PPARδ may have been up-regulated (Figure 7)
CSP showed positive effects on some factors closely related to NAFLD, such as bodyweight and lipid accumulation
The final five compounds that were screened out are flavonoids, which can combine with the screened-out target genes PPARγ, PPARα and PPARδ, and show potential as drugs for NAFLD
Summary
Non-alcoholic fatty liver disease (NAFLD) is a metabolic stress injury to the liver that is closely related to insulin resistance and is based on genetic susceptibility without a history of excessive alcohol consumption. | 5177 of the HFD group, the NRs in the CSP group exhibited a similar trend to that of the NC group, but there was no significant difference These results indicated that PPARγ and RARα may have been down-regulated in the NAFLD or high-fat diet rat model, whereas FXR, PPARα and PPARδ may have been up-regulated (Figure 7). All the docking processes had good scores (Figure 8) (Table 1)
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