Inhibition of B-cell activating factor activity using active compounds from Physalis angulata in the mechanism of nephrotic syndrome improvement: A computational approach

Nephrotic syndrome, a multifaceted medical condition characterized by significant proteinuria, has recently prompted a reorientation of research efforts toward B-cell-mediated mechanisms. This shift underscores the pivotal role played by B-cells in its pathogenesis. The aim of this study was to explore potential therapeutic pathways, with specific attention given to compounds found in <i>Physalis angulata</i>, including withanolides, such as physalins, which constitute one of the five distinct withanolide subgroups identified in <i>Physalis angulata</i>. Furthermore, the study assessed the monoclonal antibody belimumab, designed to target B-cell activating factor (BAFF) and its associated receptors (TACI, BCMA, and BAFF-R). Various research techniques were employed, encompassing data mining, bioactivity analysis, Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) profiling, molecular modeling, and docking studies. Withanolide was demonstrated as a potential inhibitor for the protein BAFF, showing a binding energy of -7.1 kcal/mol. Physalin F emerged as the leading candidate inhibitor for the protein TACI, with a binding energy of -8.3 kcal/mol. Similarly, withanolide was identified as the top inhibitor candidate for the protein BCMA, exhibiting a binding energy of -7.0 kcal/mol. The most favorable interaction with BAFF-R was physalin F, which displayed a binding energy of -8.0 kcal/mol. Moreover, molecular dynamic simulation suggested that physalin F was able to maintain protein stability, hence being a good inhibitor candidate for BAFF-R and TACI proteins. The results of this investigation demonstrated substantial promise, indicating that these withanolides and withaphysalin A compounds derived from <i>Physalis angulata</i> offer alternative avenues for B-cell targeting. Consequently, this study presents opportunities for pioneering treatments in the management of nephrotic syndrome.