Exploration on the mechanism and experimental verification of Buzhong Yiqi Decoction on retinitis pigmentosa based on network pharmacology and molecular docking
10.3760/cma.j.cn115398-20230803-00034
- VernacularTitle:基于网络药理学和分子对接探究补中益气汤对视网膜色素变性作用机制及实验验证
- Author:
Xirui YANG
1
;
Jixue WANG
Author Information
1. 河南中医药大学第一附属医院眼科，郑州 450000
- Keywords:
Bu Zhong Yi Qi Tang;
Retinal pigmentation;
Ferroptosis;
Network pharmacology;
Mechanism
- From:
International Journal of Traditional Chinese Medicine
2024;46(8):1015-1022
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the mechanism of Buzhong Yiqi Decoction in the treatment of retinitis pigmentosa (RP) based on network pharmacology; To verify it by in vitro experiments.Methods:The effective active components and corresponding targets of Buzhong Yiqi Decoction were screened by retrieving TCMSP database, and the RP-related targets were obtained by searching GeneCards, OMIM and other databases. The interaction network diagram of Buzhong Yiqi Decoction-RP was drawn by Cytascape3.7.1 software, and the core targets were extracted. DAVID online database was used to enrich and analyze gene ontology (GO) and Kyoto Encyclopedia of Genes and Genome (KEGG) pathway; the FerrDb database was searched to obtain the genes that regulate ferroptosis, and finally comprehensively analyze the relationship between the active targets of Buzhong Yiqi Decoction, RP and ferroptosis and make predictions; finally, molecular docking was performed by Auto Dock software to verify the reliability of the results. In vitro experiment, rat Muller cells were used as the research object, and LPS-induced cells were used to construct model cells in vitro. The blank group, model group, Buzhong Yiqi Decoction low-, medium- and high-dosage groups were set up, and the cell proliferation was detected by CCK-8 method; the concentrations of lactate dehydrogenase (LDH), superoxide dismutase (SOD), malondialdehyde (MDA) and ferroptosis in the cells were detected by the kit method; the expressions of HIF-1α MRNA and GPX-4, FTH-1, ACSL4 mRNA levels in cells of each group were detected by RT-PCR.Results:Totally 117 effective targets were selected from Buzhong Yiqi Decoction, and IL-6, IL-1β, EGFR, ESR1, PPARG may be the targets of Buzhong Yiqi Decoction in regulating ferroptosis and anti-RP. Buzhong Yiqi Decoction could regulate ferroptosis by mediating MAPK, HIF-1, TNF, AGE-RAGE, Toll-like receptor, IL-17, PI3K-Akt and other signal pathways. Molecular docking virtual results suggested that the quercetin, kaempferol, β-Sitosterol and IL-6, IL-1β, EGFR, ESR1, PPARG and other candidate core targets had good binding activity. Compared with the model group, the cell activity, level of SOD, LDH activity, MDA content and Fe 3+ content, IL-6 mRNA, HIF1A mRNA ,ACSL4 mRNA in each Buzhong Yiqi Decoction group significantly decreased ( P<0.05), the expressions of GPX-4 and FTH-1mRNA significantly increased ( P<0.05). Conclusion:Buzhong Yiqi Decoction may play the role of anti-inflammation and anti-ferroptosis through multiple components, multiple targets and multiple molecular pathways, thus achieving the effect of prevention and treatment of RP.
