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.

Toxicological evaluation of a polyherbal formulation on testicular function and gonadal histomorphology in exposed Wistar rats.

Introduction: Dr Iguedo Goko Cleanser® is a herbal formulation (HF) widely marketed in southern Nigeria and purported to be very efficacious for the management of various diseases including giardiasis, toilet infections, hypertension, diabetes, ulcer, impotence, low libido, low sperm count amongst others. Medicinal plants reportedly produce an array of adverse reactions capable of inducing harmful conditions, including death. Aim: This study evaluated the subchronic toxicity concern of HF on testicular function and gonadal histoarchitecture in Wistar rats. Methods: Thirty Wistar rats of both sexes were randomly divided into six groups (5/group) and were orally administered HF for 60 days. The control groups received 5 mL/kg of distilled water; the treatment groups were administered 476.24 and 158.75 mg/kg body weight of HF each for both male and female rats. Using standard procedures, semen analysis was done for all male rats. Animals were anaesthetised and sacrificed on the 62nd day; the gonads were eviscerated, weighed and fixed in 10% buffered formalin for histopathological examinations. Results: Significant (p < 0.05) increase in sperm count relative to control as well as spermatotoxic effects were observed in male rats. Histologically, the ovary presented some degrees of pathologies: cloggy appearing ovarian cortex with a display of a tumour-like cortical area, scantily displayed primordial follicles, haemorrhagic blood vessels, atretic secondary follicle, and eroding granulosa cells amongst others. Testicular histopathology showed abnormal seminiferous tubules' histoarchitecture, degenerated spermatids, distorted spermatogenic cells' orientation, and displaced spermatids into the luminal space. Conclusion: Herbal drugs are usually regarded to be completely safe due to their natural sources, however, this study discovered exposure-related toxic effects of Dr Iguedo Goko Cleanser® on testicular function and gonadal histomorphology. The findings recommend extreme caution with chronic use and avoidance whenever possible.

Antiplasmodial activity and cytotoxicity of ethanol extract of Zea mays root.

OBJECTIVE: Zea mays root decoction that has been traditionally used for the treatment of malaria by various tribes in Nigeria, was evaluated for antimalarial potential against malaria parasites using in vivo and in vitro models. MATERIALS AND METHODS: The root extract of Zea mays was investigated for antimalarial activity against Plasmodium berghei in mice using rodent malaria models; suppressive, prophylactic and curative tests and in vitro antiplasmodial activity against chloroquine-sensitive (Pf 3D7) and resistant (Pf INDO) strains of Plasmodium falciparum using SYBR green assay method. Median lethal dose and cytotoxic activity against HeLa and HEKS cells were assessed and phytochemical screening was also carried out using standard procedures. RESULTS: The LD50 value of root extract was found to be 474.34 mg/kg. The crude extract (45-135 mg/kg, p.o) showed significant (p<0.05-0.001) antimalarial activity against P. berghei infection in suppressive, prophylactic and curative tests with a prolonged survival time. The crude extract also showed moderate activity against both chloroquine-sensitive (Pf 3D7) and resistant (Pf INDO) strains of P. falciparum with an IC50 value of 71.62±3.38 µg/ml (for Pf 3D7) and 63.76±4.12 µg/ml (for Pf INDO). The crude extract was not cytotoxic to the two cell lines tested with TC50 of >100 µg/ml against both HeLa and HEKS cell lines. CONCLUSION: These results suggest that the root extract of Zea mays possesses antimalarial activity against both chloroquine-sensitive and resistant malaria and these data justify its use in ethnomedicine to treat malaria infections.

Hepatoprotective activity of the extract of Homalium letestui stem against paracetamol-induced liver injury.

OBJECTIVE: Homalium letestui Pellegr (Flacourtiaceae) has been traditionally used by the Ibibios of Southern Nigeria to treat stomach ulcer, malaria and other inflammatory diseases and Yorubas of western Nigeria as an antidote. This study evaluates the hepatoprotective properties of the ethanol extract of the plant stem. MATERIALS AND METHODS: The hepatoprotective effect of the extract of the stem of the plant (200-600 mg/kg) was evaluated by the assay of liver function parameters, namely total and direct bilirubin, serum protein and albumin, total cholesterol, alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), and alkaline phosphatase activities (ALP), antioxidant enzymes like superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx), reduced glutathione (GSH) and histopathological study of the liver. Also, GCMS analysis of n-butanol fraction of the extract was carried out. RESULTS: Administration of the extract of the stem of the plant caused a significant (p<0.05 - 0.001) dose-dependent reduction of high levels of liver enzymes (ALT, AST and ALP), total cholesterol, direct and total bilirubin as well as elevation of serum levels of total protein, albumin and antioxidant enzymes (SOD, CAT, GPx and GSH). Histology of the liver sections from extract and silymarin-treated animals showed reductions in the pathological features compared to the paracetamol-treated animals. The chemical pathological changes were consistent with histopathological observations suggesting marked hepatoprotective effect of the extract of H. letestui stem. GCMS analysis of n-butanol fraction revealed the presence of 16 bioactive compounds. CONCLUSION: The results show that the extract of H. letestui has hepatoprotective potential which may be due to the antioxidant activity of its phytoconstituents.

Hepatoprotective activity of Mammea africana ethanol stem bark extract.

OBJECTIVE: The stem bark of Mammea africana Sabine (Guttiferae), (M. africana) a common plant that has been traditionally used to treat various diseases and ailments was evaluated for hepatoprotective potentials against paracetamol-induced liver injury in rats. MATERIALS AND METHODS: The hepatoprotective effect of the stem bark extract (30-90 mg/kg) was evaluated by the assay of liver function parameters, namely total and direct bilirubin, serum protein and albumin, total cholesterol, alanine aminotransaminase (ALT), aspartate aminotransaminase (AST), and alkaline phosphatase activities (ALP), antioxidant enzymes: superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), reduced glutathione (GSH) and histopathological study of the liver. RESULTS: Administration of the stem bark extract caused a significant (p<0.05 - 0.001) dose-dependent reduction of high levels of liver enzymes (ALT, AST and ALP), total cholesterol, direct and total bilirubin as well as elevation of serum levels of total protein, albumin and antioxidant enzymes (SOD, CAT, GPx and GSH). Histology of the liver sections of extract and silymarin-treated animals showed reductions in the pathological features compared to the paracetamol-treated animals. The chemical pathological changes were consistent with histopathological observations suggesting marked hepatoprotective effect of the stem bark extract of M. africana. CONCLUSION: The results show that the stem bark extract of M. africana has hepatoprotective potential which may be due to its antioxidant activity.

Antidiarrhoeal and antiulcer activities of Hippocratea africana root extract.

The effect of ethanol root extract of H. africana on experimentally induced diarrhoea and ulcer was studied in rodents. The extract (200-600 mg/kg) considerably inhibited castor oil induced diarrhoea, small intestine transit time and castor oil induced fluid accumulation as well as indomethacin and ethanol induced ulcer models. The effect of the extract in these models was comparable to the various standard drugs used. The root extract of H. africana has antidiarrhoeal and antiulcer properties which justify its uses in ethnomedicine.