Exploring the molecular mechanism of Polygonum multiflorum in treating androgenic alopecia based on the methods of bioinformatics and molecular docking

Abstract

This study aims to research and discuss the molecular mechanism of Polygonum multiflorum (PM) to treat androgenic alopecia (APA). The target network and protein interaction network of APA of PM were established using traditional Chinese medicine molecular mechanism bioinformatics databases and disease gene databases. The core subnetworks were screened based on topological analysis, and Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses were performed, molecular docking of the 10 genes with the highest connectivity. According to the intersection of active components and potential targets of PM, 1325 common target factors were obtained. The core subnetwork composed of 66 genes was screened by topological analysis. The results of Kyoto Encyclopedia of Genes and Genomes enrichment showed that PM mainly exerts biological functions by regulating inflammatory response, oxidation stress, apoptosis, autophagy, and other pathways. The result of molecular docking shows that the binding energies of HRAS, PIK3CA, PIK3CB, and RHOA -resveratrol, -polygonin, -chrysophanol, -rheum emodin, and -rhein were all <-9 kcal/mol. PM's mechanism in treating APA may regulate the expression of PIK3CA and PIK3CB through the emodin-mediated phosphoinositide 3-kinase/protein kinase B pathway to regulate cell apoptosis. In addition, some processes, such as inhibiting inflammation, oxidative stress, and inducing melanin production, are also involved. PM has application value in treating APA and can be popularized after testing.

Keywords: Polygonum multiflorum; androgenic alopecia; bioinformatic; molecular docking; molecular mechanism.

Figure 1.

Identifying the effective components and the potential disease targets of PM.(A) GSE84839 Heat Map. Heat map of the expression of APA-associated key genes with the respective values from the GSE84839 dataset. The heat map represents each gene’s relative expression from various samples. Gene names are indicated across the x-axis with the color scale representing the relative expression; red is high, and blue is low. This visualization highlights insight into the differential expression of genes involved in APA in the dataset. (B) GSE84839 Volcano Plot. Volcano plot displaying the differential regulation of genes in the GSE84839 dataset in androgenic alopecia. The x-axis shows the gene expression and fold change with a base of 2, and the y-axis has the −log10(P value) for statistical significance. Genes that are the most significant and with the most considerable fold change are highlighted and labeled in the plot. This allows identifying the highest expressed and the lowest expressed genes in APA with surprising ease. (C) Identification of genes associated with androgenic alopecia from all results by 5 databases combined. Venn diagram showing the intersections of gene lists obtained from the 5 database sources: GeneCards, OMIM, TTD, DrugBank, and GEO. A total of 2070 disease-related genes are identified, and their overlap with drug target genes is analyzed to reveal potential targets for APA treatment. (D) Overlap of drug target genes and disease-related genes. Venn diagram showing the overlap of drug target genes with disease-related genes. The potential targets with maximum use in the treatment of androgenic alopecia are represented by a total number of 1325 common target genes. This illustrates the genes that could serve as therapeutic targets for the action of PM in APA. APA = androgenic alopecia, GEO = Gene Expression Omnibus, PM = Polygonum multiflorum.

Figure 2.

Ranks among the most highly connected genes in the core subnetwork based on MCC screening. The top 10 genes with the highest connectivity in the core subnetwork, as revealed through maximum cluster centrality (MCC) screening. In other words, the listed genes of SOS1, PIK3CA, PIK3R1, HRAS, PIK3CB, KRAS, NRAS, LCK, RHOA, and EGFR surface several important findings that link to molecular mechanisms underlying androgenic alopecia. This figure, however, neatly shows their roles in the regulatory network and gives weight to potential therapeutic targets for APA. APA = androgenic alopecia, MCC = maximum cluster centrality.

Figure 3.

An overview of the assessment of risk of bias. A summary of the risk of bias across studies is included in the analysis. The risk of bias in each study was assessed based on the following domains: selection bias, performance bias, detection bias, and reporting bias. The bias risk was depicted graphically, showing the studies as either low, high, or unclear. This summary provides insight into their methodological quality and reliability, considering these studies in the review.

Figure 4.

Molecular docking of effective ingredients of pm and core subnetwork. Molecular docking results of effective ingredients from PM with the core subnetwork target proteins. The interactions between the active components and the target proteins are depicted, with binding energies (in kcal/mol) provided for each pairwise interaction. The following protein-ligand pairs are shown: (A) HRAS-resveratrol, (B) HRAS-polygonin, (C) HRAS-chrysophanol, (D) HRAS-rheum emodin, (E) HRAS-rhein, (F) PIK3CA-resveratrol, (G) PIK3CA-polygonin, (H) PIK3CA-chrysophanol, (I) PIK3CA-rheum emodin, (J) PIK3CA-rhein, (K) PIK3CB-resveratrol, (L) PIK3CB-polygonin, (M) PIK3CB-chrysophanol, (N) PIK3CB-rheum emodin, (O) PIK3CB-rhein, (P) RHOA-resveratrol, (Q) RHOA-polygonin, (R) RHOA-chrysophanol, (S) RHOA-rheum emodin, (T) RHOA-rhein. The figure shows strong interactions between the selected compounds and target proteins, with binding energies <−9 kcal/mol indicating significant docking interactions. These findings suggest the potential of PM’s active ingredients to interact with key proteins involved in the pathogenesis of APA, making them potential therapeutic agents for the condition. APA = androgenic alopecia, PM = Polygonum multiflorum, rhein = 5-hydroxy-3-(4-hydroxyphenyl)-7-methoxy-2-methyl-1,4-benzodioxane.