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生品和醋制精油改善 CCl 诱导的肝纤维化:整合网络药理学和分子机制评价。

Essential oil from the raw and vinegar-processed ameliorate CCl-induced liver fibrosis: integrating network pharmacology and molecular mechanism evaluation.

机构信息

State Key Laboratory of Southwestern Chinese Medicine Resources, School of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu 611137, Sichuan, China.

Institute of Thai-Chinese Medicine Department of Thai Traditional and Alternative Medicines, Ministry of Public Health, Bangkok 11000, Thailand.

出版信息

Food Funct. 2021 May 11;12(9):4199-4220. doi: 10.1039/d0fo03052j.

DOI:10.1039/d0fo03052j
PMID:33870974
Abstract

Liver fibrosis, caused by multiple chronic liver injuries, is a known contributor to cirrhosis and even liver cancer. As a Traditional Chinese Medicine (TCM), Rhizoma curcumae has been extensively used in the treatment of liver fibrosis with satisfying therapeutic effects; however, its mechanism is unclear. The essential oil is the main bioactive component. The purpose of this study was to investigate the chemical profile and the pharmacological mechanisms of the essential oil of Rhizoma curcumae (EORC) against liver fibrosis by combining network pharmacology and transcriptomic technologies. A total of 37 active compounds were identified using the GC/MS system and literature mining, and the corresponding putative targets were predicted. Then, network pharmacology method was applied to identify the 168 candidate targets of EORC-alleviated liver fibrosis. String database and Cytoscape software were used to build the herb-compound-target network and protein-protein interactions (PPIs) network. Functional and pathway enrichment analysis indicated that EORC significantly influenced TGF-β1/Smads and PI3K/AKT pathways. Experimentally, we verified that EORC attenuated the severity and pathological changes during liver fibrosis progression based on the CCl4-induced liver fibrosis rat model. Transcriptomic technologies demonstrated that EORC ameliorated liver fibrosis partially by regulating the TGF-β1/Smads and PI3K/AKT pathways. In addition, the effect of vinegar-processed EORC was more significant than that of the raw one. Therefore, EORC can alleviate the severity of liver fibrosis through mechanisms predicted by network pharmacology and provide a basis for the further understanding of the application of EORC in the treatment of liver fibrosis.

摘要

肝纤维化是由多种慢性肝损伤引起的,是肝硬化甚至肝癌的已知诱因。作为一种中药,莪术已广泛用于治疗肝纤维化,疗效满意;然而,其机制尚不清楚。精油是主要的生物活性成分。本研究旨在通过网络药理学和转录组学技术,研究莪术精油(EORC)抗肝纤维化的化学成分谱和药理机制。采用 GC/MS 系统和文献挖掘法鉴定出 37 种活性化合物,并预测其相应的靶标。然后,采用网络药理学方法鉴定 EORC 缓解肝纤维化的 168 个候选靶标。利用 String 数据库和 Cytoscape 软件构建了草药-化合物-靶标网络和蛋白质-蛋白质相互作用(PPIs)网络。功能和通路富集分析表明,EORC 显著影响 TGF-β1/Smads 和 PI3K/AKT 通路。实验证实,EORC 可减轻 CCl4 诱导的肝纤维化大鼠模型中肝纤维化进展过程中的严重程度和病理变化。转录组学技术表明,EORC 通过调节 TGF-β1/Smads 和 PI3K/AKT 通路部分改善肝纤维化。此外,醋制莪术的效果比生品更显著。因此,EORC 可以通过网络药理学预测的机制减轻肝纤维化的严重程度,为进一步了解 EORC 在肝纤维化治疗中的应用提供依据。

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