Abstract
Fructus Aurantii (FA) is a traditional herbal medicine that has been widely used for thousands of years in China and possesses a variety of pharmacological effects. However, the active ingredients in FA and the potential mechanisms of its therapeutic effects have not been fully explored. Here, we applied a network pharmacology approach to explore the potential mechanisms of FA. We identified 5 active compounds from FA and a total of 209 potential targets to construct a protein-protein interaction (PPI) network. Prostaglandin G/H synthase 2 (PTGS2), heat shock protein 90 (HSP90), cell division protein kinase 6 (CDK6), caspase 3 (CASP3), apoptosis regulator Bcl-2 (Bcl-2), and matrix metalloproteinase-9 (MMP9) were identified as key targets of FA in the treatment of multiple diseases. Gene ontology (GO) enrichment demonstrated that FA was highly related to transcription initiation from RNA polymerase II promoter, DNA-templated transcription, positive regulation of transcription, regulation of apoptosis process, and regulation of cell proliferation. Various signaling pathways involved in the treatment of FA were identified, including pathways in cancer and pathways specifically related to prostate cancer, colorectal cancer, PI3K-Akt, apoptosis, and non-small-cell lung cancer. TP53, AKT1, caspase 3, MAPK3, PTGS2, and BAX/BCL2 were related key targets in the identified enriched pathways and the PPI network. In addition, our molecular docking results showed that the bioactive compounds in FA can tightly bind to most target proteins. This article reveals via network pharmacology research the possible mechanism(s) by which FA exerts its activities in the treatment of various diseases and lays a foundation for further experiments and the development of a rational clinical application of FA.
Highlights
Fructus Aurantii (FA, the unripe fruit of Citrus aurantium Linn, known as Zhike) is a traditional herbal medicine widely used for thousands of years in China
We identified the targets of the active ingredients in FA via the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and PharmMapper databases and constructed a compound-target network to analyze the potential interactions between active compounds and potential targets
In silico prescreening models were used to identify the main components of FA with favorable pharmacokinetic characteristics; total of 5 candidate compounds of FA were obtained after ADME identification (Table 1)
Summary
Fructus Aurantii (FA, the unripe fruit of Citrus aurantium Linn, known as Zhike) is a traditional herbal medicine widely used for thousands of years in China. FA exhibits a variety of pharmacological properties, such as antidepressant, antidiabetic, antinephrolithic, and anticarcinogenic properties, enhances gastrointestinal motility, and conveys cardiovascular protective effects [2, 3]. Its usage as a protective herb to treat gastrointestinal dysfunction via accelerated gastric emptying and intestinal transit has been confirmed by pharmacological studies and clinical trials [5, 6]. Other pharmacological effects of FA, such as blood lipid regulation, obesity prevention by modulating gut Evidence-Based Complementary and Alternative Medicine microbiota, and anti-inflammatory effects, have been widely reported [9, 10]. Many studies have confirmed that FA exhibits various therapeutic effects, the active ingredients and underlying mechanisms of FA have not yet been fully explored, which has complicated the modernization and clinical usage of FA. Many studies have confirmed that FA exhibits various therapeutic effects, the active ingredients and underlying mechanisms of FA have not yet been fully explored, which has complicated the modernization and clinical usage of FA. us, it is necessary to identify the bioactive substances of FA and elucidate the mechanisms of action
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