Studies on the effect of boeravinone b and withanolide a on human dendritic cell development

Abstract

Various vaccines against many pathogenic diseases have led to a dramatic decrease in the incidence of these diseases such as diphtheria, measles, mumps, pertussis, rubella, poliomyelitis, cholera, tuberculosis and tetanus worldwide. To address the problems of insignificant potency of some vaccines, such as HIV vaccine, cancer vaccine etc, studies at the mentor s lab have been performed with various new techniques to increase the efficacy of vaccines. Adjuvants, chemical and biological origins such as squalene, muramyl dipeptide, IL-2, Flt-3 and CD40L, have been studied to increase the potency of vaccines. Dendritic cells are called nature s adjuvants. Their uses as an adjuvant have been investigated by many labs, including our lab. DCbased vaccinia melanoma oncolysate vaccine (DC-melvac) was studied as adjuvant therapy for patients with malignant melanoma cancer. In continuation of investigation in vaccine adjuvant, the current study was performed to identify plant-derived compounds as promising immunoadjuvants. More specifically, effects of plant derivatives Boeravinones from Boerhaavia diffusa and Withanolides from Withania somnifera were studied for the DC immunomodulatory properties. Therefore, the current study was designed with the following objectives: 1) To screen the Boeravinones and Withanolides for drug likeness activity using bioinformatics tools. 2) To study the binding of Boeravinone B (BB) and Withanolide A (WA) on IMMs present on DC, using in silico methods. 3) To extract and purify BB and WA from B.diffusa and W.somnifera, respectively. 4) To study the development of DC from precursor DC in the medium containing BB or WA. 5) To understand the effect of BB or WA- developed DC to stimulate and proliferate antigen specific T-cells using model antigen TT, PPD and BCG.In the in silico studies, BB and WA, were identified to have drug likeness property. Molecular docking studies were performed to check the binding affinity of BB and WA with 162 human immunomodulatory receptor molecules expressed o