Systems Pharmacology Study of the Anti-Liver Injury Mechanism of Citri Reticulatae Pericarpium

Abstract

Liver diseases are mostly triggered by oxidative stress and inflammation, leading to extracellular matrix overproduction and prone to develop into liver fibrosis, cirrhosis and hepatocellular carcinoma. Liver injury (LI) refers to various pathogenic factors leading to the destruction of stem cells that then affect the liver’s normal function, causing a series of symptoms and abnormal liver function indicators. Citri Reticulatae Pericarpium (CRP) is one of the most commonly used traditional Chinese medicines; it contains flavonoids including hesperidin, nobiletin, and tangeretin. CRP has antibacterial, antioxidant, and antitumor effects that reduce cholesterol, prevent atherosclerosis and decrease LI. Here we analyzed the components of CRP and their targets of action in LI treatment and assessed the relationships between them using a systems pharmacology approach. Twenty-five active ingredients against LI were selected based on ultra-performance liquid chromatography-quadrupole/time-of-flight mass spectrometry results and databases. The drug targets and disease-related targets were predicted. The 117 common targets were used to construct a protein-protein interaction network. We identified 1719 gene ontology items in LI treatment, including 1,525 biological processes, 55 cellular components, and 139 molecular functions. These correlated with 49 Kyoto Encyclopedia of Genes and Genomes pathways. These findings suggest that CRP may counteract LI by affecting apoptotic, inflammatory, and energy metabolism modules. In vitro experiments suggested that the mechanism may involve hesperidin and naringenin acting on CASP3, BAX, and BCL2 to affect the apoptosis pathway, attenuating liver fibrosis. Naringenin significantly inhibited AKT1 phosphorylation, which in turn mediated activation of the phosphoinositide 3-kinase-Akt signaling pathways against LI. This study provides a reference for systematically exploring the mechanism of CRP’s anti-LI action and is also expands of the application of systems pharmacology in the study of traditional Chinese medicine.

Exploratory Compatibility Regularity of Traditional Chinese Medicine on Osteoarthritis Treatment: A Data Mining and Random Walk-Based Identification

“…Radix Glycyrrhizae Polysaccharide , one of the chief bioactive components in Radix Glycyrrhizae , has been reported to participate in regulation of immunity and phagocytosis, as well as anticomplement [ 25 ]. Volatile oils and flavonoids in Pericarpium Citri Reticulatae are considered to be major components, which act alone or jointly to combat inflammatory responses and lipid peroxidation, followed by attenuating immunological reaction [ 26 ]. To conclude, the therapeutic effects resulting from combinations of couplet medicines are quite different.…”

Exploration of Ziziphi Spinosae Semen in Treating Insomnia Based on Network Pharmacology Strategy

“…The higher node degree indicates that this gene may be more important, and the details of the specific gene name and its corresponding node degree are given in Supplementary Table S4 . In addition, we calculated the mean value of 106 overlapping gene degrees to be 15.05, selected all genes with value greater than the mean value [ 34 ], and generated 48 core targets of relatively more important networks with other gene interactions ( Figure 3(b) ). Moreover, to better highlight the importance of key targets, after processing these related targets using Cytoscape software, it displayed 48 genes with higher values in the inner loop of Figure 3(c) .…”

Citri Reticulatae Pericarpium alleviates postmyocardial infarction heart failure by upregulating PPARγ expression

“…CRP, a traditional Chinese herbal medicine used in the clinic for centuries, has anti-in ammatory, antioxidant, anticancer and other bene cial properties according to modern pharmacological studies [22,24,34]. In addition, CRP may be effective for diseases affecting multiple systems, such as the digestive system, the respiratory system and particularly the cardiovascular system [22,27,35]. Accumulating evidence suggests that CRP has cardioprotective effects [15,16,36].…”

“…CRP has attracted increasing attention from researchers because it has multiple pharmacologic effects and rich resources with low toxicity and costs [23]. Modern pharmacological investigations have revealed that CRP can ght against in ammation, oxidative stress, atherosclerosis, thrombus, liver injury and tumors [22,[24][25][26][27]. Our prior studies showed that CRP can alleviate cardiac hypertrophy and brosis induced by Ang II and ISO via activating PPARγ [15,16].…”