.png){kind=icon}
.png){kind=icon}
Return
Investigation of the action mechanism of Madhumega kudineer formulation against diabetic nephropathy by network pharmacology, molecular docking and dynamics strategies
.png){kind=icon}
PRE
AI
B
P
J
E
R
S
DOI：10.1016/j.hermed.2025.101061.png)
.png){kind=icon}
Original request for help.png){kind=icon}
Share.png){kind=icon}
Save
Abstract
En 中文
Introduction: Diabetic nephropathy (DN), a microvascular complication of diabetes leads to chronic kidney disease and end stage kidney disease. In this study, we aim to elucidate the major pathways and key targets involved in the therapeutic effect of Madhumega kudineer (MK-polyherbal formulation), used in the treatment of DN by network pharmacology. Methods: The common gene-targets corresponding to MK-phytochemicals and DN were used for phytochemical-target network construction, gene-ontology enrichment, KEGG pathway enrichment and protein-protein interaction (PPI) network. The major cellular pathways and the key-targets involved were further identified by KEGG enrichment. The interaction of identified key-targets with phytochemicals was investigated by in silico methods of molecular docking, molecular dynamics simulation and MM-PBSA. Results: From the PPI network of common gene-targets, 23 core-targets with degree above mean (> 83) were shortlisted and their KEGG pathway enrichment revealed AGE-RAGE complications, TNF signalling and IL-17 signalling to be the top pathways. From the cross-section of the above pathways, the key-targets identified includes AKT1, TNF-alpha and IL6. Based on the highest binding affinity, the key-target and the corresponding MKphytochemical complex were AKT1-quercetin, TNF-alpha-andrographolide and IL6-andrographolide. Molecular dynamic simulations evaluated the conformational stability of these complexes. MM-PBSA binding energy calculations revealed that van der Waals interactions predominantly drive the binding of MK phytochemicals to AKT1, TNF-alpha and IL6, with energy contributions from the hydrophobic residues in their binding regions. Conclusion: Our in-silico analysis suggests that the phytochemicals of Madhumega kudineer combats diabetic nephropathy by targeting AKT1, TNF-alpha and IL6 involved in inflammatory pathways.
Keywords:
Polyherbal formulation
Inflammatory response
Diabetic complication
Protein - protein interaction
AGE-RAGE signalling
Journal
J
IF:
1.9
Papers:
45
Citations:
0
Organization
Cited Papers