Exploring the Pharmacological Mechanisms of Ginkgo biloba Extract in the Treatment of Sensorineural Hearing Loss

Abstract

Backgrounds: Anincreasing people are suffering from sensorineural hearing loss (SNHL) and facing great psychological and physical stress. Although the extract of extract of Ginkgo biloba (EGb) has been widely used to treat SNHL for many years, underlying pharmacological mechanisms remain unclear. Methods: Active ingredients of EGb and compounds targets were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP). SNHL-related genes were obtained from GeneCards. Venny 2.1 was used to select common targets between active ingredients of EGb and SNHL, and Gene ontology (GO) enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed. Cytoscape was used to construct a network map to assess the relationship between active ingredients, interacting targets, and signaling pathways, and Chem3D, AutoDock Tools, and PyMol were employed to perform molecular docking between active ingredients and hub genes. Besides, House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were treated with cisplatin and EGb to verify target genes by quantitative Real-time PCR (q-PCR). Results: Venny diagram showing that SNHL and EGb had a total of 64 intersecting targets (core targets). The results of GO and KEGG analysis indicated that 64 core targets were involved in regulating of biological process, stabilization of cell membranes and organelles, protein binding, and diverse signaling pathways. According to the cytoscape and PPI network analyses, three genes (GSK3B, NOS3 and AKT1) and nine kinds of corresponding ingredients (kaempferol, quercetin, sesamin, luteolin, isorhamnetin, isogoycyrol, laricitrin, syringetin and chryseriol) were picked. Molecular docking demonstrates protein binding models for intersection genes and effective ingredients. Eventually, the results of q-PCR experiments further revealed that GSK3B, NOS3 and AKT1 genes exerted their functions in treatment of SNHL by EGb. Conclusions: Our findings indicate the mechanisms of action of EGb in treating SNHL. There are five active components, including luteolin, quercetin, isorhamnetin, kaempferol, and sesamin. Those ingredients exert their effects through regulating three genes (GSK3B, NOS3 and AKT1), which are involved in the PI3K-Akt signaling pathway.