Exploring the Molecular Mechanism of Aconiti Kusnezoffii Radix Ameliorates Diabetes Mellitus Type 2 Based on Systems Pharmacology
10.13748/j.cnki.issn1007-7693.20223931
- VernacularTitle:基于系统药理学探讨草乌改善2型糖尿病的分子机制
- Author:
Tingting LIU
1
;
Yue WU
2
;
Qi CHEN
3
;
Fuhou CHANG
4
;
Mengdi ZHANG
4
Author Information
1. School of Pharmacy, Inner Mongolia Medical University, Hohhot 010000, China；School of Life Sciences, Henan University, Kaifeng 475004, China
2. Pharmacy Department of Affiliated Hospital of Inner Mongolia Medical University, Hohhot 010000, China
3. School of Pharmacy, Inner Mongolia Medical University, Hohhot 010000, China；College of Traditional Chinese Medicine, China Pharmaceutical University, Nanjing 210009, China
4. School of Pharmacy, Inner Mongolia Medical University, Hohhot 010000, China
- Publication Type:Journal Article
- Keywords:
Aconiti Kusnezoffii Radix ；diabetes mellitus type 2；systematic pharmacology ； bioinformatics； molecular docking；molecular mechanism
- From:
Chinese Journal of Modern Applied Pharmacy
2024;41(5):606-618
- CountryChina
- Language:Chinese
-
Abstract:
OBJECTIVE :To explore the potential of Aconiti Kusnezoffii Radix in affecting diabetes mellitus type 2(T2DM) and the potential mechanism for T2DM related symptoms based on systematic pharmacology, bioinformatics, molecular docking and in vitro and in vivo experiments.
METHODS
The database was used to search the related chemical components of Aconiti Kusnezoffii Radix, predict the potential targets and intervene related diseases. The differential genes of T2DM relative healthy people were retrieved from GEO database, mapped with the action target of Aconiti Kusnezoffii Radix, and placed in DAVID database for biological function enrichment. The sensitivity of the target gene to T2DM was analyzed by one-way ANOVA, binary logistic regression analysis and ROC curve. The binding position and interaction force between chemical compounds of Aconiti Kusnezoffii Radix and target proteins were analyzed by molecular docking technology. The effect of Aconiti Kusnezoffii Radix and its chemical compounds on the expression of target protein was verified by T2DM model in vivo and in vitro.
RESULTS
Through database retrieval and analysis, 304 kinds of target related diseases(P value<0.05, FDR<0.05) were obtained, and T2DM with the highest degree value(Degree=59) was selected and analyzed. The 43 target genes were obtained from the intersection of differential genes in T2DM relatively healthy people and potential action targets of Aconiti Kusnezoffii Radix. A total of 9 genes with significant differences were obtained by one-way ANOVA, 5 meaningful genes were obtained by binary logistic regression analysis, and 3 genes with area under ROC curve AUC>0.5 were obtained. By molecular docking (+)-Isoboldine binds to proteins APEX1, CASP1 and CBFB, Napelline binds to proteins CBX1 and EHMT2 through different forces such as hydrogen bond interaction, ligand interaction, hydrophobic interaction, ionizability and electrostatic interaction, so as to increase the ability of ligands to target proteins. After 2 weeks of treatment with Aconiti Kusnezoffii Radix aqueous extract, Aconiti Kusnezoffii Radix may alleviated the symptoms of T2DM by improving peripheral neuropathy. Moreover, Aconiti Kusnezoffii Radix could affect the protein expression of APEX1, CASP1, CBFB, CBX1 and EHMT2 in rat liver tissue. The effect of (+)-Isoboldine and Napelline chemical compounds in Aconiti Kusnezoffii Radix on the target protein of the model in vitro was consistent with that in vivo.
CONCLUSION
It is preliminarily revealed that Aconiti Kusnezoffii Radix can be used as a potential therapeutic drug to improve T2DM peripheral neuropathy, which lays a theoretical foundation for the research and development of Chinese Mongolian medicine and the excavation of new target drugs for the treatment of T2DM.
