Phytochemical Profiling and <i>In Silico</i> Targeting of Krüppel-Like Factors 4 (KLF4) by <i>Orthosiphon stamineus</i> for CKD Intervention

The incidence of chronic kidney disease (CKD), which is believed to be between 10% to 14% worldwide, is a growing public health concern. The study's main objective was to investigate the nephroprotective and nephrocurative properties of the folk plant Orthosiphon stamineus using molecular docking and dynamics analyses to assess its potential for treating CKD. Graph-theoretical network analysis identified the transcription factor Krüppel-Like Factors 4 (KLF4) as a significant therapeutic target for CKD. Eighty-four phytochemicals were identified from public repositories and docked against the KLF4 protein, and their binding affinities were compared with those of the standard CKD drug Furosemide. Based on the docking results Neoschaftoside (-6.9 kcal/mol), Hederagenin (-6.8 kcal/mol), Stigmasterol (-6.8 kcal/mol), Orthosiphol D (-6.8 kcal/mol), Beta- Sitosterol (-6.6 kcal/mol), Eupatorin (-6.4 kcal/mol), Sinensitin (-6.4 kcal/mol) having a higher binding affinity than the standard drug Furosemide (-6.2 kcal/mol), were chosen for further studies among the 84 compounds from Orthosiphon stamineus. Furthermore, the Eupatorin and Sinensetin molecules exhibited substantial druglikeness and ADME properties, along with reduced toxicity profiles. Neoschaftoside, Eupatorin, and Sinensetin appear to establish robust and specific interactions with KLF4 that are comparable to, or even better than, those of the common medication Furosemide, according to MD simulation results. Hence, the Eupatorin and Sinensetin molecules, with further in vitro and in vivo analyses, can be used as potent and safe drug candidates for managing CKD.