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. 2023 Feb 9:2023:4934711.
doi: 10.1155/2023/4934711. eCollection 2023.

Investigation of the Potential Mechanism of Alpinia officinarum Hance in Improving Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

Xuguang Zhang  1 , Xiangyi Li  1 , Hailong Li  1 , Mingyan Zhou  1 , Yuxin Zhang  1 , Weiyong Lai  1 , Xiuwen Zheng  1 , Feihu Bai  2 , Junqing Zhang  1
Affiliations

Investigation of the Potential Mechanism of Alpinia officinarum Hance in Improving Type 2 Diabetes Mellitus Based on Network Pharmacology and Molecular Docking

Xuguang Zhang et al. Evid Based Complement Alternat Med. .

Abstract

Objective: We used network pharmacology, molecular docking, and cellular analysis to explore the pharmacodynamic components and action mechanism of Alpinia officinarum Hance (A. officinarum) in improving type 2 diabetes mellitus (T2DM).

Methods: The protein-protein interaction (PPI) network, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed to predict the potential targets and mechanism of A. officinarum toward improving T2DM. The first 9 core targets and potential active compounds were docked using Discovery Studio 2019. Finally, IR-HepG2 cells and qPCR were applied to determine the mRNA expression of the top 6 core targets of the PPI network.

Results: A total of 29 active ingredients and 607 targets of A. officinarum were obtained. T2DM-related targets overlapped with 176 targets. The core targets of the PPI network were identified as AKT serine/threonine kinase 1 (AKT1), an activator of transcription 3 (STAT3), tumor necrosis factor (TNF), tumor protein p53 (TP53), SRC proto-oncogene, nonreceptor tyrosine kinase (SRC), epidermal growth factor receptor (EGFR), albumin (ALB), mitogen-activated protein kinase 1 (MAPK1), and peroxisome proliferator-activated receptor gamma (PPARG). A. officinarum performs an antidiabetic role via the AGE-RAGE signaling pathway, the HIF-1 signaling pathway, the PI3K-AKT signaling pathway, and others, according to GO and KEGG enrichment analyses. Molecular docking revealed that the binding ability of diarylheptanoid active components in A. officinarum to core target protein was higher than that of flavonoids. The cell experiments confirmed that the A. officinarum extracts improved the glucose uptake of IR-HepG2 cells and AKT expression while inhibiting the STAT3, TNF, TP53, SRC, and EGFR mRNA expression.

Conclusion: A. officinarum Hance improves T2DM by acting on numerous components, multiple targets, and several pathways. Our results lay the groundwork for the subsequent research and broaden the clinical application of A. officinarum Hance.

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Conflict of interest statement

The authors declare that they have no conflicts of interest.

Figures

Figure 1
Figure 1
The potential targets of A. officinarum improve T2DM. (a) The component-target network diagram of A. officinarum, blue nodes: targets of A. officinarum, yellow nodes: components of A. officinarum; (b) the Venn diagram of T2DM-relative targets; (c) the Venn diagram of T2DM- and A. officinarum-related targets.
Figure 2
Figure 2
PPI network analysis of potential targets of A. officinarum and T2DM. (a) Protein-protein interaction (PPI) network, DC: degree; BC: betweenness centrality; CC: closeness centrality; (b) degree values of the top 9 target proteins.
Figure 3
Figure 3
GO and KEGG enrichment analyses of the potential targets of A. officinarum and T2DM. (a) GO enrichment analysis of the targets of A. officinarum; (b) analysis of KEGG enrichment in 20 pathways as the targets of A. officinarum; (c) the chord diagram of GO terms and core targets; (d) the chord diagram of the KEGG core pathways and core targets.
Figure 4
Figure 4
The “component-target-pathways” network of A. officinarum for T2DM. Blue nodes: the KEGG pathway of the GO-term identifier; red nodes: the potential targets of A. officinarum improve T2DM, and the redder the color of the node, the higher the degree value of the node; orange node: components of A. officinarum, and the larger the node, the greater the degree value of the node; yellow node: A. officinarum; green node: T2DM.
Figure 5
Figure 5
Heat map of LibDock scores for active compounds in A. officinarum and the core target proteins. The X-axis represents the key targets; Y-axis represents the bioactive compounds. The redder the color, the higher the LibDock score.
Figure 6
Figure 6
The docked complexes of 9 target proteins along with their strongest binding compounds. (a) AKT1-hexahydrocurcumin, (b) STAT3-octahydrocurcumin, (c) TNF-hexahydrocurcumin, (d) TP53-hexahydrocurcumin, (e) SRC-5-hydroxy-7-(4″-hydroxy-3″-methoxy-phenyl)-1-phenyl-3-heptanone, (f) EGFR-1,7-diphenyl-5-hydroxy-3-heptanone, (g) MAPK1-5R-hydroxy-7-(4-hydroxy-3-methoxyphenyl)-1-(4-hydroxyphenyl)-3-heptanone, (h) ALB-octahydrocurcumin, and (i) PPARG-hexahydrocurcumin.
Figure 7
Figure 7
The effects of AOE on IR-HepG2 cells. (a) Cell viability; (b) quantitative fluorescence determined by the extent of glucose uptake; (c) the mRNA expression of AKT; (d) the mRNA expression of STAT3; (e) the mRNA expression of TNF; (f) the mRNA expression of TP53; (g) the mRNA expression of SRC; (h) the mRNA expression of EGFR. All values are expressed as the mean ± SD (n ≥ 3). ∗P < 0.05, ∗∗P < 0.01, when compared with the model control group; ##P < 0.01 and ###P < 0.001 when compared with the control group.
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