In vitro effects of NIPRISAN (Nix‐0699): a naturally occurring, potent antisickling agent

Abstract

Summary. Among the various potential antisickling agents tested, hydroxyurea (HU) has been the most effective compound used for the treatment of patients with sickle cell disease (SCD). Although HU is effective in many patients, not all patients respond to this drug. In addition, some patients reveal adverse effects, including myelosuppression. In an attempt to find other effective agents with less adverse effects, we investigated the antisickling effect of NIPRISAN (Nix-0699). We found that Nix-0699, an ethanol/water extract from indigenous plants, has a strong antisickling effect. The concentration of Nix-0699 required to inhibit 50% of erythrocyte sickling was about 0AE05 mg/ml. As for the kinetics of polymerization, addition of 0AE05 lg/ml Nix-0699 caused a sixfold prolongation of the delay time prior to deoxy-Hb S polymerization when compared with that of untreated Hb S samples. The solubility of deoxy-Hb S significantly increased upon treatment with Nix-0699. Analysis of the effect of Nix-0699 on the Hb S oxygen affinity indicated that the drug slightly shifted the oxygendissociation curve of Hb S toward the left without any apparent change in the Hill coefficient. These results suggest that the antisickling properties of Nix-0699 may involve direct interaction with Hb molecules. Incubation of red blood cell (RBC) suspensions with various concentrations of Nix-0699 did not dehydrate RBCs, cause haemolysis, increase the amount of denatured Hb, nor form met-Hb. In view of the outcome of this study, Nix-0699 may be a promising option for the treatment of patients with SCD.

Treating sickle cell disease by targeting HbS polymerization

“…97,98 Niprisan inhibits in vitro sickling and increases both the solubility and delay time of solutions of deoxy-HbS, albeit in a highly nonphysiological buffer. 99 Moreover, the extract prolonged the survival of transgenic sickle mice after acute hypoxic challenge. 100 A recent phase 1B dose-escalation study of 26 HbSS and HbS/b 0 -thalassemia patients found that SCD-101 was well tolerated and, at higher doses, it seemed to relieve chronic pain and fatigue but had no impact on Hb levels or hemolysis.…”

Étude de l’activité antifalcemiante et de la thermo- et photo-dégradation des anthocyanes de <i>Centella asiatica, Thomandersia hensii et Maesopsis eminii</i>

“…Dans certaines régions d'Afrique, les porteurs du trait drépanocytaire représentent jusqu'à 20% de la population avec une prévalence en Afrique Centrale de 25 à 30% (Egunyomi et al, 2009 ;Iyamu et al, 2002 ;Moody et al, 2003 ;Ogunyemi et al, 2008;Voet et Voet, 1998). Deux pourcents de la population en République Démocratique du Congo (RDC) sont touchés par cette maladie, soit plus d'un million de personnes (Mpiana et al, 2012).…”

“…L'utilisation des plantes médicinales semble pourtant ces dernières années donner un peu plus d'espoir. En effet, plusieurs plantes utilisées en médecine traditionnelles africaine contre cette maladie génétique ont montré in vivo l'activité antifalcémiante (Akjie and Fung, 1992 ;Elekwa et al, 2005 ;Iyamu et al, 2002 ;Ibrahim, 2007 ;Egunyomi et al, 2009 ;Ogunyemi et al, 2008).…”

Blood samples collected under venous oxygen pressure from patients with sickle cell disease contain a significant number of a new type of reversibly sickled cells: Constancy of the percentage of sickled cells in individual patients during steady state

“…These results suggest that the percentage of sickled cells in the peripheral blood decreases after a painful episode. This change was confirmed in transgenic (Tg) sickle mice that were exposed to hypoxia [15][16][17][18]. We previously found that UnExp-blood collected from the antecubital vein of steady-state patients with SCD contains varying percentages of a new type of reversibly sickled cells with blunt edges [1,2].…”