Elucidating the active interaction mechanism of phytochemicals withanolide and withanoside derivatives with human serum albumin

Abstract

Withania somnifera (Ashwagandha) is an efficient medicinal plant known in Ayurveda and Chinese medicine since ancient times, whose extracts are consumed orally as food supplement or as a health tonic owing to its several restorative properties for various CNS disorders, inflammation, tumour, stress, rheumatism etc. In this study, we have analyzed the binding interaction of four derivatives of Withania somnifera (Withanolide A, Withanolide B, Withanoside IV and Withanoside V) with HSA because of their important pharmacological properties. To unravel the binding between derivatives of Withania somnifera and HSA, fluorescence spectroscopy was used. Binding studies were further studied by molecular docking and dynamics and results confirmed greater stability upon binding of derivatives with HSA. Circular dichroism data illustrated change in the secondary structure of protein upon interaction with these derivatives, particularly the helical structure was increased and β-sheets and random coils were decreased. Furthermore, morphological and topological changes were observed using AFM and TEM upon binding of ligands with HSA indicating that HSA-withnoside/withanolide complexes were formed. All the results cumulatively demonstrate strong binding of withanosides and withanolides derivatives with serum albumin, which should further be explored to study the pharmacokinetics and pharmacodynamics of these derivatives.

The Marine-Derived Triterpenoid Frondoside A Inhibits Thrombus Formation

“…These contradictory findings may be explained by a different sensibility of the cell types used. Moreover, the binding to soluble proteins within PRP, such as human serum albumin (HSA) or immunoglobulins, may have interfered with the uptake of frondoside A into platelets [22]. Therefore, higher concentrations of the compound were needed to exert detectable antithrombotic effects in our experimental setting.…”

Leishmanicidal Activity of Withanolides from Aureliana fasciculata var. fasciculata

“…In silico results of our study also corroborate with the one performed by Singh et al [43] in which withanolide A from Withania somnifera (L.), with neuropharmacological activity, presented high PPB, passive permeability and a fast and wide distribution kinetics in vitro. Also, Dubay et al [44] demonstrated that withanolides and withanosides of W. somnifera have a strong binding to serum albumin. In addition, further structure-based drug design with withanolides is required.…”

Investigation of food microstructure and texture using atomic force microscopy: A review

“…For example, four extracts from Withania somnifera were interacted with human serum albumin to explore their pharmaceutical properties. AFM showed that the derivatives could bind to human serum proteins resulting in greater stability, thus enhancing the scope for development of such steroidal derivatives (Dubey, Kallubai, Sarkar, & Subramanyam, 2018). AFM has been used to explore the interaction between marine bacterial GY785 exopolysaccharide and transforming growth factor-β1, showing that the interaction can promote the differentiation of some tissues.…”