# Therapeutic role of Crateva religiosa in diabetic nephropathy: Insights into key signaling pathways

## TL;DR

This study explores how Crateva religiosa may help treat diabetic nephropathy by identifying key bioactive compounds and signaling pathways involved.

## Contribution

The study combines computational and empirical methods to identify novel phytoconstituents and their molecular targets in diabetic nephropathy.

## Key findings

- Five phytoconstituents from Crateva religiosa showed potential therapeutic activity in diabetic nephropathy.
- Common targets like AKT1, PPARG, and PTGS2 were found to have strong molecular affinities.
- Key pathways like PI3K-Akt and AGE-RAGE were linked to inflammation and oxidative stress in diabetic nephropathy.

## Abstract

Crateva religiosa, a plant used in traditional medicine, is valued for its bioactive properties. Traditional approaches are more accepted worldwide as a cost effective alternatives being used in network pharmacology to explore the complex interactions of drug targets among molecular pathways. The study investigated the potential of Crateva religiosa’s phytoconstituents using meticulous computational analysis and empirical confirmation. The IMPPAT, GeneCards and DisGeNET data bases were used to obtain the active moieties and disease targets respectively. Crateva phytoconstituent’s DN-target network and protein-protein interaction (PPI) network were developed and analyzed using the STRING online platform and Cytoscape software. GO and KEGG analyses were conducted using the g: profiler databases while the process of molecular docking involved the use of MOE software. The screening process identified dillapiole (CR-C1), beta ionone (CR-C2) 10-epi-γ-eudesmol (CR-C3), cis/trans linalool oxide (CR-C4/5) and nerolidol (CR-C6), as potential active phytoconstituents of C. religiosa and AKT1, PPARG, PTGS2, EGFR, ESR1, JAK2, MAPK1, PARP1, GSK3B, and PPARA as matching targets in DN. The enrichment analysis revealed that the common targets were primarily linked to inflammatory response, oxidative stress, immunological modulation, and cell death. The main signal pathways suggested were PI3K-Akt, AGE-RAGE, and IL-17. Moreover, molecular docking analysis determined that the AKT1, PPARG and PTGS2 are the essential targets that had a good affinity for their respective active molecules.