A network pharmacology‐based approach to explore the effects of Chaihu Shugan powder on a non‐alcoholic fatty liver rat model through nuclear receptors

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 proteinprotein 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.

Clinical Significance of HSPD1/MMP14/ITGB1/miR-6881-5P/Lnc-SPARCL1-1:2 RNA Panel in NAFLD/NASH Diagnosis: Egyptian Pilot Study

“…Accordingly, they proposed using Gremlin 1 as a biomarker and potential therapeutic target in complications of obesity such as NASH [ 35 ]. In addition, Nie et al proposed that PPARγ and RARα mRNAs are down-regulated in the NAFLD rat model [ 36 ]. Similarly, Pirola et al found that miR-122, miR-192 and miR-375 miRNAs were up-regulated in simple steatosis and even more so in NASH cases [ 37 ].…”

Potential Molecular Mechanisms of Chaihu‐Shugan‐San in Treatment of Breast Cancer Based on Network Pharmacology

“…Among them, gallic acid (source: Shaoyao), oxidized paeoniflorin (source: Shaoyao), paeoniflorin (source: Shaoyao), paeoniflorin (source: Shaoyao), glycyrrhizin (source: Gancao), naringin (source: Chenpi, Zhiqiao), hesperidin (source: Chenpi, Zhiqiao), and ferulic acid (source: Chuanxiong) had higher contents, all above 1000 mg/g [ 28 ]. Although some studies have comprehensively elucidated the treatment of depression [ 6 , 29 ], nonalcoholic fatty liver disease [ 30 , 31 ] and functional dyspepsia [ 5 ] by Chaihu-Shugan-San, no studies have comprehensively elucidated the mechanism of Chaihu-Shugan-San in the treatment of breast cancer. Therefore, with the aid of network pharmacology, this study analyzed the specific molecular mechanism of Chaihu-Shugan-San in the treatment of breast cancer from a microscopic perspective.…”

Metabolic Impact of Flavonoids Consumption in Obesity: From Central to Peripheral

“…Through a network pharmacological approach Nie et al [ 262 ] highlighted that Chaihu shugan powder (CSP) may exert its beneficial effects against NAFLD through the interaction of its main compounds with nuclear receptors. Through a molecular docking approach, they screened PPARγ, FXR, PPARα, RARα and PPARδ and quercetin, kaempferol, naringenin, isorhamnetin and nobiletin interactions.…”

“…The NAFLD-induced rats treated with CSP exhibited ameliorated effects in body weight, hepatic histopathology and serum and liver lipids. Moreover, the mRNA levels of Pparγ, FXR, Pparα and Rarα were modified suggesting nuclear receptors regulation as a potential molecular mechanism underlying the effects of CSP [ 262 ].…”