Potential of Three Ethnomedicinal Plants as Antisickling Agents

Abstract

Sickle cell disease (SCD) is a genetic blood disorder that affects the shape and transportation of red blood cells (RBCs) in blood vessels, leading to various clinical complications. Many drugs that are available for treating the disease are insufficiently effective, toxic, or too expensive. Therefore, there is a pressing need for safe, effective, and inexpensive therapeutic agents from indigenous plants used in ethnomedicines. The potential of aqueous extracts of Cajanus cajan leaf and seed, Zanthoxylum zanthoxyloides leaf, and Carica papaya leaf in sickle cell disease management was investigated in vitro using freshly prepared 2% sodium metabisulfite for sickling induction. The results indicated that the percentage of sickled cells, which was initially 91.6% in the control, was reduced to 29.3%, 41.7%, 32.8%, 38.2%, 47.6%, in the presence of hydroxyurea, C. cajan seed, C. cajan leaf, Z. zanthoxyloides leaf, and C. papaya leaf extracts, respectively, where the rate of polymerization inhibition was 6.5, 5.9, 8.0, 6.6, and 6.0 (×10−2) accordingly. It was also found that the RBC resistance to hemolysis was increased in the presence of the tested agents as indicated by the reduction of the percentage of hemolyzed cells from 100% to 0%. The phytochemical screening results indicated the presence of important phytochemicals including tannins, saponins, alkaloids, flavonoids, and glycosides in all the plant extracts. Finally, gas chromatography–mass spectrometry analysis showed the presence of important secondary metabolites in the plants. These results suggest that the plant extracts have some potential to be used as alternative antisickling therapy to hydroxyurea in SCD management.

Phytocomponents from Anacardium occidentale, Psidium guajava, and Terminalia catappa altered membrane osmotic stability of sickle erythrocytes

“…Additionally, aromatic compounds such as L-phenylalanine and its derivative L-phenylalanine benzyl ester are effective agents, even at relatively low concentrations, against HbS polymerization and have been proposed to be effective therapeutic agents for the management of SCD [72][73][74][75][76]. The improved sickle erythrocyte osmotic stability in samples containing petroleum ether extract of T. catappa appeared to suggest that aromatic compounds in petroleum ether extract of T. catappa attenuated HbS polymerization-induced hemolysis in hypotonic solutions as previously described [35,59,70,71]. From another perspective, the antioxidant phytocomponents from plant materials viz.…”

“…Furthermore, the use of mathematical models had revealed the relationship between sickle hemoglobin (HbS) polymerization and membrane morphology, osmotic properties, viscoelasticity, rheology, and related physicochemical characteristics of sickle erythrocytes as empirically described [67][68][69]. By implication, phytocomponents that deterred HbS aggregation and polymerization improved sickle erythrocyte membrane stability [35,59,70,71] within limits of their permeability across the biomembrane system as previously described [72]. In line with the present findings, the presence of isothiocyanates, a notable anti-HbS polymerization phytochemicals [70,71], in ethylacetate extract of A. occidentale obviously contributed, in parts, in stabilizing the sickle erythrocyte membrane against osmotic stress.…”

“…Sickle cell disease (SCD) is a hereditary autosomal recessive erythrocyte disorder caused by mutant hemoglobin molecules (sickle cell hemoglobinopathy; α 2 β 2 s ) that polymerize under low oxygen tension within the microvasculature. Intra-erythrocytic polymerization of deoxygenated sickle hemoglobin, in turn, promotes distortion of the erythrocytes that take up the sickle morphology [33][34][35]. The functional and structural defective erythrocytes elicit multiple clinical disorders, notably; severe anemia, vasoocclusion, multiple organ damage, and splenomegaly associated secondary infections [36].…”

“…Sickle erythrocytes are relatively fragile and frequently undergo spontaneous osmotic lysis because of low elasticity and rigidity of their membrane structures [35]. The enhanced membrane fragility index is further exacerbated by high oxidative stressed status of sickle erythrocytes [39][40][41].…”

Privileged substructures for anti-sickling activity via cheminformatic analysis

“…Nevertheless, the side effects of this drug include neutropenia, bone marrow suppression, elevation of hepatic enzymes, anorexia, nausea, vomiting and infertility. 10,11 Recently, on July 7, 2017, the U.S. FDA approved L-glutamine oral powder (Endari) as the rst new drug in 20 years for SCD, which acts by reducing acute complications in adults and children of 5 years and older. Although its mechanism of action is not fully understood, the drug is found to be involved in the oxidative stress phenomena of SCD.…”