Exploring the potential mechanism of Kaixinsan powder for the same pathogenesis of PTSD and anxiety based on network pharmacology and molecular docking: A review

Abstract

Background: Post-traumatic stress disorder (PTSD) and anxiety are common mental illnesses and there are many similar pathogenesis and clinical manifestations between PTSD and anxiety. Kaixinsan powder (KXS), a commonly used prescription in traditional Chinese medicine, has been widely used to treat PTSD and anxiety. This study aims to explore the potential mechanisms of KXS for the same pathogenesis of PTSD and anxiety using a network pharmacology approach.

Methods: The bioactive components and relevant target genes of KXS were obtained from the database about Traditional Chinese Medicine. The key genes of PTSD and anxiety were derived from disease databases. Subsequently, the network of protein-protein interaction and a network of "drug-components-disease-targets" was constructed. In order to treat PTSD and anxiety, gene ontology enrichment and signaling pathway enrichment were analyzed by using R language and components-core targets associated were validated by molecular docking.

Results: One hundred three targets of KXS in treating PTSD and anxiety were identified. The results of protein-protein interaction analysis and molecular docking indicated that AKT1 and IL-6 were crucial targets. Moreover, KEGG analysis has shown that neuroactive ligand-receptor interaction, calcium signaling pathway, and cAMP signaling pathway may play crucial roles in treating PTSD and anxiety. Ten biological process, 10 molecular function, and 10 cellular component were revealed via gene ontology analysis.

Conclusions: The network pharmacology study and molecular docking indicated that KXS treated anxiety and PTSD by multiple components, targets, and signaling pathways. These results provide an important reference for subsequent basic research on PTSD and anxiety.

Figure 1.

Schematic diagram of the process of network pharmacology analysis with molecular docking.

Figure 2.

Venn diagram showed the overlapping gene among PTSD, anxiety and KXS. KXS = Kaixinsan powder, PTSD = Post-traumatic stress disorder.

Figure 3.

The medicine-components-overlapping targets-diseases network construction. The network included 167 nodes and 577 edges. Green rectangles represented overlapping targets, purple rhombus represented bioactive components, blue triangles represented medicine, red oval represented KXS and Wathet rectangle represented diseases. KXS = Kaixinsan powder.

Figure 4.

Network of PPI analysis. PPI network analysis included the interaction of 103 overlapping protein. PPI = protein–protein interaction.

Figure 5.

Proteins with top 10 node degree. The top 10 proteins in terms of node degree included AKT1, IL-6, CASP3, NOS3, PTGS2, JUN, ESR1, SLC6A4, COMT, and CAV1.

Figure 6.

The top 10 gene-ratio term in BP, CC, and MF. The y axis showed the BP, CC, and MF respectively. The x axis showed the enrichment scores of these term, and the size of the circles mean that counts of gene-ratio of each term. BP = biological process, CC = cellular components, MF = molecular function.

Figure 7.

Network construction of MF in GO enrichment analysis. The network consisted of 42 nodes and 117 edges. Blue circles represented targets gene, and purple rhombus represented core MF. GO = gene ontology, MF = molecular function.

Figure 8.

Network construction of BP in GO enrichment analysis. The network consisted of 78 nodes and 232 edges. Blue circles represented targets gene, and purple rhombus represented core BP. BP = biological process, GO = gene ontology.

Figure 9.

Network construction of CC in GO enrichment analysis. The network consisted of 51 nodes and 179 edges. Blue circles represented targets gene, and purple rhombus represented core CC. CC = cellular components, GO = gene ontology.

Figure 10.

The top 10 gene-ratio term in KEGG enrichment analysis. The y axis shown the term of KEGG signaling pathways and the x-axis showed the enrichment scores of these term, and the size of the circles indicated the counts of gene-ratio in each pathway. KEGG = Kyoto encyclopedia of genes and genomes.

Figure 11.

Network construction of KEGG enrichment analysis. The network consisted of 73 nodes and 152 edges. Blue circles represented targets gene, and purple rhombus represented core signaling pathways. KEGG = Kyoto encyclopedia of genes and genomes.

Figure 12.

Mapping of neuroactive ligand-receptor interaction.

Figure 13.

Mapping of calcium signaling pathway.

Figure 14.

Chemical structures of core target proteins and positive drugs: (A) beta-sitosterol, (B) Stigmasterol, (C) Fumarine, (D) Tenulin, (E) Andrographolide, and (F) Resveratrol.

Figure 15.

The combined figures of the 3D molecular models as followed: (A) beta-sitosterol-AKT1, (B) Stigmasterol-AKT1, (C) Fumarine-AKT1, (D) Tenulin-AKT1, (E)positive drug-AKT1, (F) beta-sitosterol-IL6, (G) Stigmasterol-IL6, (H) Fumarine-IL6, (I) Tenulin-IL6, and (J) positive drug-IL6.

Figure 16.

The 3D molecular models between AKT1 and drug/component as followed: (A) beta-sitosterol-AKT1, (B) Stigmasterol-AKT1, (C) Fumarine-AKT1, (D) Tenulin-AKT1, and (E) positive drug-AKT1.

Figure 17.

The 3D molecular models between IL-6 and drug/component as followed: (A) beta-sitosterol-IL6, (B) Stigmasterol-IL6, (C) Fumarine-IL6, (D) Tenulin-IL6, and (E) positive drug-IL6. IL = interleukin.