Hematopoietic development during embryogenesis involves the interaction of extrinsic signaling pathways coupled to an intrinsic cell fate that is regulated by cell-specific transcription factors. Retinoic acid (RA) has been linked to stem cell self-renewal in adults and also participates in yolk sac blood island formation.

cdx4, a caudal-related homeodomain-containing transcription factor, functions as a regulator of hox genes, thereby playing a critical role in anterior-posterior (A–P) patterning during embryogenesis. In zebrafish, homozygous deletion of the cdx4 gene results in a mutant phenotype known as kugelig (kgg), with aberrant A-P patterning and severe anemia characterized by decreased gata1 expression in the posterior lateral mesoderm. To identify pathways that interact with cdx4 during primitive hematopoiesis, we conducted a chemical genetic screen in the cdx4 mutant background for compounds that increase gata1 expression in cdx4 mutants. Among 2640 compounds that were tested, we discovered two compounds that rescued gata1 expression in the cdx4 mutant embryos. The strongest rescue was observed with bergapten, a psoralen compound found in bergamont oil. Another member of the psoralen family, 8-MOP was also found to rescue gata1 expression in cdx4 mutant embryos. The psoralen compounds also disrupted normal A-P patterning of embryos. These compounds modify the cdx4 mutant phenotype, and will help elucidate signaling pathways that act downstream or parallel to the cdx4-hox pathway.

The blood glucose- lowering potentials of ethanol leaf extract of Annona muricata were studied. Thirty wistar albino rats were divided into six groups of five rats per group. Group 1 served as “Normal control” animals and received normal rat pellets and water. Diabetes mellitus was induced in Groups 2, 3, 4, and 5 by intraperitoneal injection of alloxan (130 mg/kg). Group 6 rats were administered with 400 mg/kg daily of the extract without induction; group 3 rats were treated with glibenclamide (5 mg/kg body weight), groups 4 and 5 received 200 mg/kg and 400 mg/kg body weight of A. muricata leaf extract daily respectively throughout the duration of the experiment of 14 days. Group 2 rats were induced but not treated with any drug, thus it served as the “Negative control” group. Quantitative phytochemical analysis of the leaf extract was carried out using the Association of Official Analytical Chemists (AOAC) methods. Acute toxicity test of the leaf extract of A. muricata was determined using 12 rats by Lorke’s toxicity testing method. The blood glucose levels of the animals in each group were determined using Accu-chek test strip method. The weights of the animals were determined using a standard electronic weighing balance. The result of the quantitative phytochemical analysis of the leaf showed that the ethanol leaf extract contains the following: phenols (74 mg/100 g), flavonoids (3.70 mg/100 g), tannins (2.95 mg/100 g), oxalate (6.48 mg/100 g), terpenoid (13.88 mg/100 g), phytates (130 mg/100 g), saponins (6800 mg/100 g), alkaloids (570 mg/100 g), cardiac glycoside (1690 mg/100g). Acute toxicity studies showed that LD50 was 3807.89 mg/kg body weight. The results of the average blood glucose levels (mg/dl) of the rats in each group were group 1, 82.6071±7.7524, group 2, 309.3571±163.6923, group 3, 226.7143±132.8182, group 4, 146.5000±140.1465, group 5, 150.4783±81.8340, and group 6, 83.4643±12.5329 for each group respectively. The average body weights of the rats in each group were group 1, 192.8571±22.5844, group 2, 185.7143±33.6759, group 3, 177.1429±36.67500, group 4, 219.2857±21.2908, group 5, 119.5455±23.5993, and group 6, 191.7857±25.2475. The findings from this study suggest that ethanolic leaf extract of A. muricata has notable effect in lowering blood glucose levels in diabetic rats and is a more potent drug in the treatment and management of diabetes mellitus and oxidative stress- related diseases.