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Outline
Through network pharmacology and molecular docking technology, combined with in vivo experiment verification through aged db/db mice, we explored the anti-neuroinflammation mechanism of Dracocephalum rupestre Hance in aging type 2 diabetes. Neuroinflammatory targets were collected through Gene Cards, and nerve related differential genes (DEGs) in elderly patients with diabetes were screened by GEO NCBI database; 56 component targets and 31 component targets were obtained by Venny 2.1.0 software from core component targets of Dracocephalum rupestre Hance between neuroinflammatory targets and DEGs; protein-protein interaction (PPI) networks were constructed using STRING database, visualize PPI and medicine-composition-target network through Cytoscape software, and the Top 10 core targets were elected using Maximum Clique Centrality (MCC); GO (gene ontology) functional enrichment and KEGG (kyoto encyclopedia of genes and genes) pathway analysis were conducted by DAVID database. It was found that the neuroprotection effect of Dracocephalum rupestre Hance mainly include alleviated aging diabetes neuroinflammation through regulated MAPK, NF-κB and other pathway proteins. Molecular docking results showed that the core active ingredients of Dracocephalum rupestre Hance, chlorogenic acid, diosmetin, and kaempferol, have good binding activity with targets AKT1, IL-1β, BCL2, and HMOX1. In vivo experiments showed that Dracocephalum rupestre Hance can reduce blood glucose and lipid levels in aging db/db mice, ameliorate the disorder of liver tissue cell arrangement and lipid vacuoles, and reduce the level of serum pro-inflammatory cytokines; down-regulate the expression of brain TNF-α, IL-1β, TLR4, and nuclear NF-κB; inhibit the overactivation of Iba-1 in mouse brain. What's more, Dracocephalum rupestre Hance could decreased the activation of NLRP3 inflammasome. This study preliminarily revealed that the therapeutic effect of Dracocephalum rupestre Hance on aging diabetes encephalopathy may be related to improve the neuroinflammatory signal pathway, such as the regulation of TLR4/NF-κB, inhibition of NLRP3 inflammasome, etc. This experiment was approved by the Medical Ethics Committee of Shenyang Pharmaceutical University (No. SYPU-IACOC-2024-1016-103).
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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