Betulinic and ursolic acids from Nauclea latifolia roots mediate their antimalarial activities through docking with PfEMP-1 and PfPKG proteins.

BACKGROUND: Chemotherapies target the PfEMP-1 and PfPKG proteins in Plasmodium falciparum, the parasite that causes malaria, in an effort to prevent the disease's high fatality rate. This work identified the phytochemical components of Nauclea latifolia roots and docked the chemical compounds against target proteins, and examined the in vivo antiplasmodial effect of the roots on Plasmodium berghei-infected mice. METHODS: Standard protocols were followed for the collection of the plant's roots, cleaning, and drying of the roots, extraction and fraction preparation, assessment of the in vivo antiplasmodial activity, retrieval of the PfEMP-1 and PfPKG proteins, GCMS, ADME, and docking studies, chromatographic techniques were employed to separate the residual fraction's components, and the Swis-ADME program made it possible to estimate the drug's likeness and pharmacokinetic properties. The Auto Dock Vina 4.2 tool was utilized for molecular docking analysis. RESULTS: The residual fraction showed the best therapeutic response when compared favorably to amodiaquine (80.5%) and artesunate (85.1%). It also considerably reduced the number of parasites, with the % growth inhibition of the parasite at 42.8% (D2) and 83.4% (D5). Following purification, 25 compounds were isolated and characterized with GCMS. Based on their low molecular weights, non-permeation of the blood-brain barrier, non-inhibition of metabolizing enzymes, and non-violation of Lipinski's criteria, betulinic and ursolic acids were superior to chloroquine as the best phytochemicals. Hence, they are lead compounds. CONCLUSION: In addition to identifying the bioactive compounds, ADME, and docking data of the lead compounds as candidates for rational drug design processes as observed against Plasmodium falciparum target proteins (PfEMP-1 and PfPKG), which are implicated in the pathogenesis of malaria, the study has validated that the residual fraction of N. latifolia roots has the best antiplasmodial therapeutic index.

Antioxidant potentials and effects on the hematology and osmotic fragility scores of a polyherbal formulation used in Southeast Nigeria.

Background In this study, the hematological and antioxidant potential as well as the osmotic fragility effects of a Nigerian polyherbal formulation were evaluated. Materials and methods A total of 40 fats were divided into four groups of 10 rats each. Group 1 served as the control group, and the rest were assigned increasing daily oral administration of the extract for 28 days. At the end of treatment, blood was collected for hematological and osmotic fragility studies. The free radical scavenging effect of the extract was investigated via different in vitro models as well. Results Results showed that the nitric oxide scavenging and 2,2-diphenyl-1-picrylhydrazyl (DPPH) activities of the extract were significant (p < 0.05) and compared favorably with that of vitamin C. At 200 and 400 µg/mL, the nitric oxide scavenging activities for Ajumbise Polyherbal Extract (APE) were 60.71 ± 0.25% and 59.49 ± 0.98%, respectively, whereas for the same concentrations of vitamin C, 74.60 ± 0.25% and 85.24 ± 0.14 scavenging activities were obtained. The (DPPH) activity at 100 µg/mL was 81.24 ± 0.02% for the extract and 96.22 ± 0.18% for vitamin C. However, at all concentrations, the extract had significantly lower Ferric Reducing Antioxidant Power (FRAP) activity than vitamin C. Red blood cell counts (RBCC), hemoglobin and packed cell volume values (PCV) were significantly lowered only in groups treated with 400 and 800 mg/kg of the extract (p < 0.05), whereas other RBCC parameters and white blood cell counts (WBCC) were not significantly affected (p < 0.05). Platelet (PLT) count was also significantly lowered in all extract-treated groups. The extract also significantly reduced RBCC percentage hemolysis (p < 0.05). Conclusions Ajumbise polyherbal may be free of hematoxicity and may improve the integrity of the RBC membrane due to its appreciable antioxidant activity.