Abstract
BackgroundTraditional Chinese medicine (TCM) has a long history of treating glaucoma with remarkable effects, but there is no clear conclusion on its mechanism.MethodsNetwork pharmacology and molecular docking were used to analyze the mechanism and targets of TCM in the treatment of glaucoma, and baicalein was used to treat chronic ocular hypertension animal models rats for observation.ResultsThe results of animal experiments showed that baicalein could significantly reduce intraocular pressure (IOP) in a rat model of chronic ocular hypertension and protect the structure of the retina and optic nerve, as shown by hematoxylin–eosin (H&E) staining and transmission electron microscopy (TEM). Reducing the apoptosis of retinal ganglion cells (RGCs) by upregulating the expression of the antiapoptotic protein BCL-2 is basically consistent with the results of molecular docking. In the network pharmacology analysis, many key proteins of biological pathways involved in the herbal therapeutic processes in glaucoma, such as threonine kinase 1 (AKT1, core protein of PI3K/AKT signaling), tumor protein p53 (TP53, a tumor suppressor gene coding tumor protein P53), signal transducer and activator of transcription 3 (STAT3, core protein of JAK/STAT signaling), interleukin 6 (IL-6) and interleukin 17 (IL-17, proinflammatory factors), were identified. Their interactions built complicated chain reactions in the process of glaucoma.ConclusionBy combining the analysis of network pharmacology and animal experimental results, baicalein could effectively improve the symptoms of glaucoma and reduce RGC apoptosis, suggesting that the potential mechanism of TCM in treating glaucoma is related to regulating inflammation and cellular immunity and reducing apoptosis.
Highlights
Glaucoma, an optic neuropathy, has become a leading cause of irreversible vision loss due to its unpredictable morbidity and atypical initial symptoms, resulting in profound visual impairment worldwide
Herbal data collection The active ingredients of Erigeron breviscapus, Radix salviae, Lycii fructus, Croci stigma and Ginkgo folium were acquired from the Traditional Chinese Medicine Systems Pharmacology (TCMSP) Database, which focuses on Traditional Chinese medicine (TCM) [15], under the screening conditions of oral bioavailability (OB) ≥ 30%
We analyzed the gene chip GSE9944 and related platform files GPL571 and GPL8300 obtained from GEO datasets by searching the key term “glaucoma”, and the results provided 940 differential genes (DEGs), which were exhibited as heatmaps and volcano plots using R software (Fig. 2a, b)
Summary
An optic neuropathy, has become a leading cause of irreversible vision loss due to its unpredictable morbidity and atypical initial symptoms, resulting in profound visual impairment worldwide. The management of IOP, including drugs, surgical treatments and prognostic estimates, is the only verified method that has been widely used in the clinic to slow disease progression [5,6,7]. Due to the importance of RGCs in the pathology of glaucoma and the limits of current treatments, ophthalmological practitioners and researchers have paid more attention to the neuroprotection and regeneration of RGCs [9, 10]. TCM is widely used in the prevention and treatment of glaucoma in China, and some studies have found profound neuroprotective effects of TCMs [11]. We constructed glaucoma-target drug and protein–protein interaction (PPI) networks based on herbal active ingredients and drug-disease common targets acquired from different databases and performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Traditional Chinese medicine (TCM) has a long history of treating glaucoma with remarkable effects, but there is no clear conclusion on its mechanism
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