Potential of isoquercitrin as antisickling agent: a multi-spectroscopic, thermophoresis and molecular modeling approach

Abstract

Sickle cell disease is an inherited disease caused by point mutation in hemoglobin (β-globin gene). Under oxygen saturation, sickle hemoglobin form polymers, leading to rigid erythrocytes. The transition of the blood vessels is altered and initiated by the adhesion of erythrocytes, neutrophils and endothelial cells. Sickle Hemoglobin (HbS) polymerization is a major cause in red blood cells (RBC), promoting sickling and destruction of RBCs. Isoquercitrin, a medicinal bioactive compound found in various medicinal plants, has multiple health benefits. The present study examines the potential of isoquercitrin as an anti-sickle agent, showing a significant decrease in the rate of polymerization as well as sickling of RBCs. Isoquercitrin-induced graded alteration in absorbance and fluorescence of HbS, confirmed their interaction. A negative value of ΔG° strongly suggests that it is a spontaneous exothermic reaction induced by entropy. Negative ΔH° and positive ΔS° predicted that hydrogen and hydrophobic binding forces interfered with a hydrophobic microenvironment of β6Val leading to polymerization inhibition of HbS. HbS-Isoquercitrin complex exhibits helical structural changes leading to destabilization of the HbS polymer as confirmed by CD spectroscopy. MST and DSC results indicate greater changes in thermophoretic mobility and thermal stability of sickle hemoglobin in the presence of isoquercitrin, respectively. These findings were also supported by molecular simulation studies using DOCK6 and GROMACS. Hence, we can conclude that isoquercitrin interacts with HbS through hydrogen bonding, which leads to polymerization inhibition. Consequently, isoquercitrin could potentially be used as a medication for the treatment of sickle cell disease.

Communicated by Ramaswamy H. Sarma

Keywords:

• Sickle hemoglobin
• isoquercitrin
• fluorescence spectroscopy
• molecular modeling
• hb s polymerization inhibition

Acknowledgments

The authors are indebted to the central instrumentation facility of the Savitribai Phule Pune University, Pune. We are also grateful to all the authorities of the Sickle Cell Unit, Sane Guruji Hospital, MAM’s Sumatibhai Shah Ayurved Mahavidyalaya, Pune and sickle cell patients who agreed to provide their blood for this research. The authors thank to Dr. Sivaramaiah Nallapeta and Dr. Saji Menon form NanoTemper Technologies, Bangalore, India for help in MST analysis.

Disclosure statement

The authors declare that they have no conflict of interest.

Additional information

Funding

This research was supported by Grant DST-SERB, (GOI A-738) and DIC MHRD GOI (A-694).