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.

Gongronema latifolium modulates Rauwolfia vomitoria-induced behaviour and histomorphology of the cerebral cortex / Gongronema latifolium modula los cambios de comportamiento e histomorfología de la corteza cerebral inducidos por Rauwolfia vomitoria

Rauwolfia vomitoria (RV) has potent sedative effect, which may result in severe unpleasant consequences if not controlled. This necessitated this study on the effect of Gongronema latifolium (GL) on RV-induced behaviour, biochemical activities, and histomorphology of the cerebral cortex. Eighteen male Wistar rats of average weight 266 g were grouped into three (1­3). Group 1 was the control administered 0.5 mL of Tween®20, while groups 2 and 3 were administered 150 mg/kg of RV, and a combination of 150 mg/kg of RV and 200 mg/kg of GL (RV+GL), respectively for seven days. Twelve hours after treatments, open field neurobehavioral test was carried-out and the animals euthanized. Their sera were analyzed, and their cerebral cortices routinely processed by H&E method. There was lower (p<0.05) ambulatory, rearing and freezing activities in the RV group, while there was no difference in aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase activities, as well as serum cholesterol and triglycerides levels in all the groups. Cerebral cortical neurohistology of RV and RV+GL groups showed most neurons appearing hypertrophied with pyknotic nuclei in some, and less cellular population compared with the control group. RV produces sedative behaviour, and cerebral cortical neurohistological changes, which GL combination may help modulate.

Rauwolfia vomitoria (RV) tiene un efecto sedante potente, el que puede provocar graves consecuencias si no es controlado. Se estudió el efecto de Gongronema latifolium (GL) sobre el comportamiento inducido por RV, como también en las actividades bioquímicas, e histomorfología de la corteza cerebral. Dieciocho ratas macho Wistar con un peso promedio de 266 g, fueron separadas en tres Grupos (1­3). El Grupo 1 (control) recibió 0,5 mL de Tween® 20, mientras que a los Grupos 2 y 3 se les administró, durante siete días, 150 mg/kg de RV y una combinación de 150 mg/kg de RV y 200 mg/kg de GL (RV + GL), respectivamente. Doce horas después de los tratamientos y pruebas neuroconductuales de campo abierto, los animales fueron sacrificados. Se analizaron los sueros y cortezas cerebrales, los cuales fueron procesados y teñidos on HE. Se observó menor actividad ambulatoria y de congelación (p<0,05) en el grupo RV, mientras que no hubo diferencia en la actividad aspartato aminotransferasa sérica y de fosfatasa alcalina, así como tampoco en los niveles de colesterol y triglicéridos séricos en todos los grupos. La neurohistología cortical cerebral de los grupos RV y RV + GL mostró que la mayoría de las neuronas aparecen hipertrofiadas con núcleos picnóticos, y una menor cantidad celular en comparación con el grupo control. La RV produce un comportamiento sedante, y cambios neurohistológicos a nivel de la corteza cerebral lo que podría ser modulado al combinarse con GL.

Urate synthesis and oxidative stress in phenytoin hepatotoxicity: the role of antioxidant vitamins.

Phenytoin is known to induce microsomal enzymes including xanthine oxidase which catalyzes uric acid synthesis with superoxides as byproducts, thus contributing to the oxidative stress of phenytoin hepatotoxicity. To investigate the role of antioxidant vitamins in ameliorating phenytoin induced hepatic changes through possible actions on xanthine oxidase activities as measured by urate concentration. Growing albino rats of Wistar strain were randomly divided into 8 groups of 7 rats each. Group 2, 3, 4, 5, 6, 7 and 8 were treated with phenytoin alone, phenytoin + folic acid, phenytoin + vitamin E, phenytoin + vitamin E + vitamin C, phenytoin + vitamin C, phenytoin + folic acid + vitamin E and phenytoin + vitamin E + vitamin C + folic acid respectively while animals in group 1 were given normal saline to serve as control. Serum concentrations of uric acid, albumin, total protein and the activities of aspartate and alanine aminotransferases (AST and ALT) and catalase were measured spectrophotometrically using appropriate commercial reagent kits. Result showed that administration of phenytoin alone caused significant (p < 0.05) increase in serum levels of globulin, uric acid, AST and ALT activities while the levels of albumin and catalase were reduced significantly (p < 0.05). Supplementation of phenytoin treatment with vitamins resulted in various degrees of protection. However, the elevated level of uric acid in serum was not significantly (p < 0.05) affected by any of the vitamins used and there was no significant correlation between the activities of aminotransferases and uric acid concentration in the vitamin treated animals as was observed between aminotransferases and catalase. The findings in this study suggest that antioxidant vitamins were able to ameliorate phenytoin hepatotoxic effects by improving oxidant radicals removal in the animals but would not inhibit further generation of the superoxides by xanthine oxidase activity and that xanthine oxidase may contribute significantly to the oxidative stress of phenytoin therapy.

Acute toxicity, biochemical and haematological study of Aframomum melegueta seed oil in male Wistar albino rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Aframomum melegueta is a popular medicinal plant in Nigeria believed to have many agents acting in different ways to bring about human health benefits. This study aimed to determine the acute toxicity, identify some phytochemicals known to be present in this plant and the possible effects on lipid profile, haematological indices and biomarker of prostate and cardiac dysfunction. MATERIALS AND METHODS: Twenty four Wistar rats (284-326 g) were used in four groups of six animals. Group 1 (control) received normal saline; groups 2, 3 and 4, received intraperitoneal injection of 27.39, 54.77 and 82.16 mg/kg body weight of the extract respectively for 7 days. Haematological and biochemical parameters were measured. RESULTS: Alkaloids, flavonoids, saponins, tannins, cardiac glycosides, terpenoids and steroids were identified in this plant extract. The LD50 was 273.86 mg/kg body weight. Prostate Specific Antigen (PSA) decreased significantly in group 2. Testosterone increased significantly in all the test groups compared to the control. Cardiac troponin I (0 ng/dl) was recorded for the test groups while the control had 1.69 ± 0.12 ng/dl. Lipid profile results showed increase in HDL and decrease in total cholesterol and LDL-cholesterol. Haemoglobin (Hb) and Red Blood Cells count (RBC) decreased significantly in group 4. White Blood Cells count (WBC), Mean Cell Volume (MCV), Mean Cell Haemoglobin (MCH) and Mean Cell Haemoglobin Concentration (MCHC) did not change significantly. CONCLUSION: Aframomum melegueta seed oil has the potential of ameliorating benign prostatic hyperplasia (BPH) and cardiac dysfunction as indicated by testosterone, PSA, lipid profile and troponin I levels. The LD50 of 273.86 mg/kg body weight is indicative of mild toxicity. The lower than normal Hb, RBC confirms the possibility of toxicity.

Vitamin e supplementation with rauwolfia vomitoria root bark extract improves hematological indices.

BACKGROUND: Vitamin supplementation in Rauwolfia vomitoria root bark extract administration may interact and impact significantly on hematology of albino Wistar rats. AIM: In this investigation we studied vitamin E supplementation with Rauwolfia vomitoria root bark extract on the hematology of experimental animals. MATERIALS AND METHODS: Forty two rats weighing 200 - 230 g were randomly selected into six groups of seven animals each. Group 1 animals serve as controls; group 2 received vitamin E (10 IU/kg body weight). Groups 3 and 4 were given the extract (150 and 300 mg/kg body weight) respectively. Groups 5 and 6 were given vitamin E (10 IU/kg body weight), the extract (150 and 300 mg/kg body weight) respectively. The extract and the vitamin were administered daily by oral intubation. Blood samples analyzed for hematological indices. RESULTS: Decrease in white blood cell count (WBC) was observed, indicating improved immunity of animals. Extract at 150 and 300 mg/kg body weight with and without vitamin E affected hemoglobin and packed cell volume. CONCLUSION: Rauwolfia vomitoria with or without vitamin E improved animal's immunity and enhances their hematology. Interaction of vitamin E with the extract affects medicinal therapeutics of this plant.

Evaluation of calabash chalk effect on femur bone morphometry and mineralization in young wistar rats: A pilot study.

BACKGROUND: Calabash chalk, a popularly consumed geophagic material in Nigeria has been reported to contain lead, arsenic, alpha lindane, endrin, and endosulfan 11 among other pollutants. AIM: The continuous exposure of young children to this chalk necessitated this study on the bone morphometry and mineralization in young Wistar rats. MATERIALS AND METHODS: Fourteen young (weanling) Wistar rats of both sexes weighing 54-72 g were assigned into two groups of seven animals each. Group I served as control, while group II was the test group (TG). 40 mg/ml of C. chalk was administered as suspension to the test animals in group II. Animals in the control group were orally treated with 1ml of distilled water. Administration of the C. chalk in the animals lasted for 28 days, and the animals were sacrificed on day 29, using chloroform anaesthesia. The femur bones were dissected out, cleaned of flesh and sun-dried. The lengths and weights of the femur bones were measured using graphite furnace atomic mass spectrophotometer. RESULTS: Results showed 1.6% decrease in body weight change in the TG, insignificant decreases in the weights and lengths of both the right and left femur bones, and significant decreased (P < 0.0126) organ-somatic index, and femur bones concentrations (mg/l) of zinc, phosphate, carbonate, calcium, sodium, and potassium (P < 0.05). CONCLUSION: In conclusion, this study showed that C. chalk may alter growth rate, and cause de-mineralization in the femur bone, hence, it may be detrimental to bone growth.

Effect of folic acid and vitamin B(12) administration on phenytoin induced toxicity in rats.

Folic acid and vitamin B(12) are very important vitamins needed for normal cellular metabolic activities. The effects of folic acid and vitamin B(12) on liver integrity of growing Wistar albino rats following therapeutic dose of phenytoin administration were investigated. The activities of serum AST, ALT, ALP were investigated. Serum total protein level and lipid profile were also measured as indices of biochemical changes. The ingestion of phenytoin alone in rats significantly reduced serum protein while AST, ALT activities incresed as compared to the control (P<0.05). Supplementation of phenytoin with oral administration of 70microgram/kg body wt of folic acid resulted in a significant reversal in serum total protein and suppression in serum AST and ALT activities. Vitamin B(12) supplementation did not afford any significant protection against the effect of phenytoin ingestion but rather phenytoin toxicity was exacerbated in this study. However, the combined effects of vitamin B(12) and folic acid ameliorated the effects of phenytoin on serum enzymes of experimental rats. The effect of combination of phenytoin with folic acid or folic acid and vitamin B(12) is an interesting finding. Supplementation of phenytoin with folic acid or combination of these vitamins may be recommended for the purpose of ameliorating the adverse biochemical changes which are associated with phenytoin therapy. Further work is ongoing to help elucidate the effects of phenytoin and these vitamins on oxidative stress inducing mechanism.