Unveiling anti-hypertensive potential of maize silk bioactive compounds: transcriptomics-integrated in silico approach

Hypertension, a leading risk factor for acute myocardial infarction, has risen by 31% over the past 25 years. Angiotensin-converting enzyme (ACE) is a key component of the renin–angiotensin–aldosterone system (RAAS), which a key regulator of blood pressure and fluid balance. Recent studies show that maize silk (Zea mays) proteins suppress ACE activity and lower systolic blood pressure in hypertensive rats, highlighting their potential as natural antihypertensive agents. The objective of the study was to examine and compare the expression profiles of genes involved in the synthesis of bioactive compounds across several maize silk cultivars and to determine the efficacy of these bioactive compounds against hypertension. An integrated in-silico bioinformatics approach incorporating transcriptomic analysis, DFT calculations, molecular docking, and molecular dynamics simulations was deployed to screen maize silk bioactive compounds, characterizing their stability and therapeutic potential against human anti-hypertensive target proteins. Transcriptomic profiling revealed 57 differentially expressed genes, implicated in fatty acid biosynthesis and triterpenoid metabolic processes. Additionally, eight hypertension proteins were found among 617 proteins from the OMIM and DisGeNet databases that typically target the 13 biotic agents that are categorized as hypertensive proteins. Comparative genotypes studied, the W22 maize silk exhibited a significantly stronger transcriptional response compared to B73, Mo17, and Mo17×B73 hybrid. Literature-based analysis identified 3 established hypertension-related targets, including ACE in the RAAS pathway, with exploratory analysis of nuclear receptors PPARG, PPARD and VDR involved in vascular and metabolic regulation, selected for molecular docking studies. The binding energy of β-Sitosterol with PPARD and PPARG was found − 13.47 kcal/mol and − 12.97 kcal/mol, whereas the binding energy of Linoleic acid with PPARG is − 8.22 kcal/mol, and the binding energy of Oleic acid with VDR was found to be − 9.52 kcal/mol. The study showed that current bioactive molecules from different types of maize had excellent potential binding affinity with the targeted receptors. It demonstrates how different maize cultivars may be used medicinally to treat hypertension.