Sanguinarine (SGN) is a benzophenathridine
alkaloid extracted from Sanguinaria canadensis plant. SGN is incriminated in epidemic
dropsy (ED) characterized by
multiple-organ failure and
anemia. Nevertheless, how SGN leads to
anemia of ED remains poorly understood. This study was thus initiated to investigate the interaction of SGN with human red blood cells (RBCs) and to delineate associated molecular mechanisms.
Heparin- and
EDTA-anticoagulated blood was collected from healthy participants and whole blood was analyzed for a complete blood count, while isolated RBCs were examined for hemolytic and eryptotic markers following exposure to 1-100 μM SGN for 24 h at 37 °C.
Calcium was measured by Fluo4/AM,
hemolysis by
hemoglobin leakage, membrane scrambling by
Annexin V-FITC, cell size by forward scatter (FSC), cell granularity by side scatter (SSC), and oxidative stress by
H2DCFDA. SGN led to increased Fluo4 fluorescence and dose-dependent
hemolysis which was not ameliorated by exclusion of extracellular Ca2+ but was nevertheless sensitive to hyperosmotic conditions and to the presence of
aspirin. SGN also caused significant increase in
Annexin V-positive cells, decreased FSC and SSC values, and elevated DCF fluorescence. Moreover, significantly reduced lymphocyte and basophil percentages along with selective toxicity to platelets was noted. Collectively, SGN possesses
sucrose- and
cyclooxygenase-sensitive hemolytic potential and elicits eryptosis characterized by Ca2+ accumulation,
phosphatidylserine externalization, morphological alterations including cell shrinkage and loss of granularity, and oxidative stress. In conclusion, this report reveals a novel activity of SGN against human RBCs and informs prospective policies in ED prevention and management.