A network pharmacology-based approach to explore the effects of Chaihu Shugan powder on a non-alcoholic fatty liver rat model through nuclear receptors
A network pharmacology-based approach to explore the effects of Chaihu Shugan powder on a non-alcoholic fatty liver rat model through nuclear receptors
复制标题
基于网络药理学的方法探讨柴胡疏肝散通过核受体对非酒精性脂肪肝大鼠模型的影响
DOI：
10.1111/jcmm.15166
复制
发表时间：
2020-03-18
影响因子：
5.3
通讯作者：
Yang, Qinhe
中科院分区：
文献类型：
--
作者：
Nie, Huan;Deng, Yuanjun;Yang, Qinhe
非酒精性脂肪性肝病(NAFLD)的发病机制尚不完全清楚，目前尚无有效的药物治疗方法。核受体(NRs)是NAFLD的重要生物学参与者，显示出巨大的治疗潜力。柴胡疏肝散(CSP)是一种治疗非酒精性脂肪肝(NAFLD)的中药方剂，但其有效成分及作用机制尚不清楚。我们采用了多个数据库的网络药理学方法进行基因本体(GO)浓缩分析和分子复合体检测(MCODE)方法进行蛋白质-蛋白质相互作用(PPI)分析，并使用分子对接方法筛选NR靶标并确定相应的CSP组分。筛选结果通过NAFLD大鼠模型进行了验证，该模型用于解释CSP和NAFLD之间的可能关系。最后，我们筛选了PPAR-γ、FXR、PPAR-α、RAR-α和PPAR-Delta作为目的基因，以栎素、山奈酚、柚皮苷、异鼠李素和诺比林为目的化合物。采用高效液-质联用法对这5种成分进行了检测，结果与PPAR-γ、PPARα和PPAR Delta的对接实验结果相吻合。CSP干预后，NAFLD模型大鼠体重、肝组织病理学、血清和肝脂等指标均有明显改善，PPAR-γ、FXR、PPAR-α和RAR-α的mRNA水平均有明显变化。本研究的结果表明，CSP在NAFLD模型中具有愈合作用，用网络药理学方法筛选NR靶点并确定相应的CSP组分是解释CSP改善NAFLD机制的一种实用策略。
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 PPAR gamma, FXR, PPAR alpha, RAR alpha and PPAR delta 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 PPAR gamma, PPAR alpha and PPAR delta. 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 PPAR gamma, FXR, PPAR alpha and RAR alpha 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.