Unveiling the anticancer potential of genus Aerva as therapeutics for CLL (Chronic Lymphocytic Leukemia): from plant to patient.

The genus Aervacomprises diverse medicinal plant species traditionally used for various therapeutic purposes, yet their pharmacokinetic and toxicological profiles remain largely uncharacterized. This study aimed to evaluate a library of 125 phytochemicals derived from Aerva species using comprehensive in silico approaches. Drug-likeness, ADME parameters, and toxicity profiles were assessed using SwissADME and ProTox-II platforms. Six compounds (AJ26, AJ30, AJ39, AJ43, AJ47, AJ55) exhibited optimal pharmacokinetic properties, including high gastrointestinal absorption, favorable lipophilicity (log P: 1.54-2.56), and acceptable water solubility. All selected compounds met multiple drug-likeness criteria and showed no PAINS alerts. Toxicity analysis revealed low risk for hepatotoxicity, carcinogenicity, and immunotoxicity. Three GEO datasets (GSE22529, GSE26725 and GSE50006) were examined to investigate their therapeutic relevance in chronic lymphocytic leukemia (CLL). 164 common differentially expressed genes (DEGs) were identified, which were primarily associated with pathways of B-cell activation and immunity. The protein-protein interaction analysis identified the CD22, CD38, and CCR6 as strong hub genes, with CD22 had the highest diagnostic performance (average AUC = 0.939). Molecular docking showed that all the molecules showed good interactions with the corresponding receptors such as AJ26-CD38, AJ30-CD22 and AJ43-CCR6. These findings show that Aerva-derived compounds as interesting candidates for future preclinical development in phytochemical-based therapeutics.