Flavonoids in Astragali Radix Functions as Regulators of CDK2, VEGFA and MYC in Osteoporosis and Type 1 Diabetes Mellitus

Abstract

Background: People with type 1 diabetes mellitus (T1DM) are significantly more likely to have osteoporosis (OP). Astragali Radix is a Chinese herbal medicine containing various active ingredients, and several clinical trials have been reported to use it to treat OP and T1DM, respectively. Objective: To evaluate the targets and potential mechanisms of Astragali Radix administration on OP and T1DM. Methods: The targets of Astragali Radix were identified using the Traditional Chinese Medicine Systems Pharmacology (TCMSP) database. The OP and T1DM datasets were downloaded from the Gene Expression Omnibus (GEO) database. The weighted gene correlation network analysis (WGCNA) method was used to identify the co-expression genes associated with OP and T1DM. In addition, the common gene targets of OP and T1DM were screened using two public databases. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses were performed using the R tool. After the validation of key genes, molecular docking was performed to visualize small molecule-protein interactions. Results: The compound target network mainly contained 17 compounds and 147 corresponding targets. There were 561 GO items and 154 signaling pathways in KEGG, mainly including the AGE-RAGE signaling pathway in diabetic complications and osteoclast differentiation. The results of molecular docking showed that flavonoids were the top compound of Astragali Radix, which had a high affinity with CDK2, VEGFA, and MYC. Conclusion: Flavonoids in Astragali Radix may regulate multiple signaling pathways through MYC, CDK2, and VEGFA, which may play a therapeutic role in OP and T1DM.