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. 2022 Mar 31:2022:1106353.
doi: 10.1155/2022/1106353. eCollection 2022.

Study on Closely Related Citrus CMMs based on Chemometrics and Prediction of Components-Targets-Diseases Network by Ingenuity Pathway Analysis

Qixuan Mu  1 , Yaping Zhang  1 , Ying Cui  1 , Xin Chai  1 , Junlian Liu  2 , Yongzhi Li  2 , Huijuan Yu  1 , Yuefei Wang  1
Affiliations

Study on Closely Related Citrus CMMs based on Chemometrics and Prediction of Components-Targets-Diseases Network by Ingenuity Pathway Analysis

Qixuan Mu et al. Evid Based Complement Alternat Med. .

Abstract

As the representatives of closely related Chinese medicinal materials (CMMs) originated from Rutaceae family, Aurantii fructus immaturus (AFI), Aurantii fructus (AF), Citri reticulatae pericarpium viride (CRPV), and Citri reticulatae pericarpium (CRP) have better functions in regulating qi and promoting gastrointestinal motility. However, differences in the quality of closely related Citrus CMMs have not yet been revealed until now. Herein, this study focused on the systematic differentiation and in-depth understanding of closely related Citrus CMMs by a strategy integrating chemometrics and network pharmacology. Determined by ultra performance liquid chromatography, the content of nine flavonoids showed obvious fluctuations in the decoction pieces from different species (Citrus aurantium Linnaeus and Citrus reticulate Blanco) with decreasing levels in the samples of ripe fruits. Decoction pieces from the different species and ripening stages were well distinguished by orthogonal projection to latent structure-discriminate analysis (OPLS-DA) and cluster analysis. As a result, four active components including narirutin, naringenin, hesperidin, and 3,5,6,7,8,3',4'-heptemthoxyflavone were filtered out by variable importance for the projection (VIP) value (VIP > 1.0), which were regarded as chemotaxonomic markers. Furthermore, a components-targets-diseases network was constructed via ingenuity pathway analysis (IPA), and the correlations were predicted between four chemotaxonomic markers, 223 targets, and three diseases including colitis, breast cancer, and colorectal cancer. The obtained results will be of great significance for identifying closely related Citrus CMMs and conduce to improving the resource utilization of CMMs.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
The representative UPLC chromatograms of mixed reference solution (a) and sample solutions of CRPV (b), CRP (c), AF (d), and AFI (e). (1. Nar, 2. Nan, 3. Hed, 4. Ned, 5. Por, 6. Nag, 7. Not, 8. Hep, and 9. Tar).
Figure 2
Figure 2
Optimization of extraction conditions by “spider-web” mode, including extraction solvent, solid-liquid ratio, and ultrasonic time.
Figure 3
Figure 3
The relative content of nine flavonoids in 80 batches samples of four closely related Citrus CMMs.
Figure 4
Figure 4
Discrimination of four closely related Citrus CMMs by OPLS-DA (a), and VIP values of the tested compounds (b). The compounds were marked as red, which had important effects on the differentiation of samples.
Figure 5
Figure 5
Clustering heatmap analysis based on flavonoids' content in four decoction pieces.
Figure 6
Figure 6
Top 10 pathways in targets associated chemotaxonomic markers (a). Network diagram of components-targets-diseases (b). (Blue represents the chemotaxonomic markers, red represents the disease, and other colors represent the targets in different locations).
See this image and copyright information in PMC

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