Identification of the active ingredients and pharmacological effects of Kuntai capsules in the treatment of primary ovarian insufficiency: A review

Abstract

Kuntai capsules are effective in controlling primary ovarian insufficiency (POI). However, the precise mechanisms underlying the pharmacological effects of Kuntai capsules remain unclear. This study aimed to screen the active components and underlying mechanisms of Kuntai capsules for POI treatment using network pharmacology protocols and molecular docking technology. Potential active constituents in the chemical composition of Kuntai capsules were obtained from the Traditional Chinese Medicine System Pharmacology Database. Targets for POI were obtained from the Online Mendelian Inheritance in Man and Gene Cards database. All target data were integrated to identify the active ingredients of POI treatment. Enrichment analyses were performed using the Database for Annotation, Visualization, and Integrated Discovery database. The STRING database and Cytoscape software were used for protein-protein interaction network construction and core target identification. Finally, a molecular docking analysis of the active components and core targets was performed. A total of 157 ingredients related to POI were identified. Enrichment analysis showed that these components might participate in the mitogen-activated protein kinase, tumor necrosis factor, phosphoinositide-3-kinase/AKT serine/threonine kinase 1, and forkhead box O signaling pathways. Further protein-protein interaction network analysis revealed that the core targets were Jun proto-oncogene, AKT serine/threonine kinase 1, tumor protein P53, interleukin 6, and the epidermal growth factor receptor. Molecular docking analysis showed that baicalein was the most active ingredient with the highest affinity for the core targets. This study identified baicalein as the core functional component and elucidated the potential pharmacological effects of Kuntai capsule in the treatment of POI.

Figure 1.

Flow chart of the study.

Figure 2.

(A) Venn diagrams showing the common molecules of Kuntai capsule ingredients and POI-related targets. (B) The drug ingredients-POI targets network. The square nodes represent POI-related targets; lines represent interaction relationships; and ellipse nodes represent Kuntai capsule ingredients. M1= (+)-catechin; M2 = (2R)-2-[(3S,5R,10S,13R,14R,16R,17R)-3,16-dihydroxy-4,4,10,13,14-pentamethyl-2,3,5,6,12,15,16,17-octahydro-1H-cyclopenta[a]phenanthren-17-yl]-6-methylhept-5-enoic acid; M3 = (3S,5R,8R,9R,10S,14S)-3,17-dihydroxy-4,4,8,10,14-pentamethyl-2,3,5,6,7,9-hexahydro-1H-cyclopenta[a]phenanthrene-15,16-dione; M4 = (R)-canadine; M5 = 5,2’-dihydroxy-6,7,8-trimethoxyflavone; M6 = 5,7,2,5-tetrahydroxy-8,6-dimethoxyflavone; M7 = 5,7,4’-trihydroxy-6-methoxyflavanone, M8 = 5,7,4’-trihydroxy-8-methoxyflavone, M9 = acacetin, M10 = baicalein, M11 = kaempferol, M12 = oroxylin a, M13 = paeoniflorin, M14 = quercetin, M15 = stigmasterol, POI = primary ovarian insufficiency.

Figure 3.

Enrichment analysis. (A) Analysis of the top 20 GO terms (P < .05), (B) analysis of the top 20 KEGG pathways (P < .05). GO = gene ontology, KEGG = Kyoto encyclopedia of genes and genomes.

Figure 4.

Network visualization. (A) PPI network of 157 intersected targets with an interaction score ≥ 0.7. (B) Hub proteins of the PPI network identified by the MMC method. The darker the color, the higher the degree of the node. MMC = maximal clique centrality, PPI = protein-protein interaction.

Figure 5.

Molecular docking of baicalein with hub proteins. (A) Baicalein-JUN (binding energy: −5.520). (B) Baicalein-AKT1(binding energy: −5.784). (C) Baicalein-TP53 (binding energy: −7.860). (D) Baicalein-IL-6 (binding energy: −6.323). (E) Baicalein-EGFR (binding energy: −5.240). AKT1 = AKT serine/threonine kinase 1, EGFR = epidermal growth factor receptor, IL-6 = interleukin 6, JUN = Jun proto-oncogene, TP53 = tumor protein P53.