Objectives: Diabetic nephropathy (DN) is one of the most prevalent secondary complications associated with diabetes mellitus. Decades of research have implicated multiple pathways in the etiology and pathophysiology of diabetic nephropathy. There has been no reliable predictive biomarkers for the onset or progression of DN and no successful treatments are available.
Methods: In the present study, we explored the datasets of RNA sequencing data from patients with Type II diabetes mellitus (T2DM)-induced nephropathy to identify a novel gene signature. We explored the target bioactive compounds identified from Azanza garckeana, a medicinal plant commonly used by the traditional treatment of diabetes nephropathy.
Results: Our analysis identified lymphotoxin beta (LTB), SRY-box transcription factor 4 (SOX4), SOX9, and WAP four-disulfide core domain protein 2 (WFDC2) as novel signatures of T2DM-induced nephropathy. Additional analysis revealed the pathological involvement of the signature in cell-cell adhesion, immune, and inflammatory responses during diabetic nephropathy. Molecular docking and dynamic simulation at 100 ns conducted studies revealed that among the three compounds, Terpinen-4-ol exhibited higher binding efficacies (binding energies (ΔG) = -3.9~5.5 kcal/mol) against the targets. The targets, SOX4, and SOX9 demonstrated higher druggability towards the three compounds. WFDC2 was the least attractive target for the compounds.
Conclusion: The present study was relevant in the diagnosis, prognosis, and treatment follow up of patients with diabetes induced nephropathy. The study provided an insight into the therapeutic application of the bioactive principles from Azanza garckeana. Continued follow-up invitro validations study are ongoing in our laboratory.
Keywords: Azanza garckeana; biochemical parameter; dyslipidemia; hepatopathy; nephropathy.
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