Naringin binds to protein disulfide isomerase to inhibit its activity and modulate the blood coagulation rates: Implications in controlling thrombosis

Currently used antithrombotic drugs are beset with several drawbacks which necessitates the need for new and cheaper alternatives. Protein disulfide isomerase (PDI) is secreted in the blood plasma in cellular stress conditions and initiates the thrombus formation. A screening of library of natural compounds revealed that naringin had a high binding affinity for the PDI (-8.2 kcal/mol). Recombinant PDI was purified using the affinity chromatography. Incubation of purified PDI (3 mu M) with naringin (0-100 mu M, pH 7.4, 25 degrees C) partially modulated its conformation. Consequently, the fluorescence emission spectra of the PDI binding to naringin were assessed using the Stern-Volmer equation, which indicated an association constant of 2.78 x 104 M-1 suggesting an appreciable affinity for the naringin, with a unique binding site. An insulin turbidity assay showed that PDI activity is decreased in the presence of naringin indicating inhibition. Molecular dynamic simulation studies showed the changes in the PDI structure on binding to the naringin. Incubation of naringin (80 mu M) in fresh human plasma along with exogenous PDI (175 nM) showed a significant delay in the intrinsic and extrinsic coagulation pathways. We show that naringin is able to modulate the PDI conformation and activity resulting in altered blood coagulation rates.

Automated summary

Current antithrombotic drugs have drawbacks, prompting the search for new and cheaper alternatives. This study found that naringin has high binding affinity for PDI, altering its conformation and activity, and thereby affecting blood coagulation rates.