Phytochemicals and bioactive compounds effective against acute myeloid leukemia: A systematic review.

This systematic review identified various bioactive compounds which have the potential to serve as novel drugs or leads against acute myeloid leukemia. Acute myeloid leukemia (AML) is a heterogeneous hematopoietic malignancy that arises from the dysregulation of cell differentiation, proliferation, and cell death. The risk factors associated with the onset of AML include long-term exposure to radiation and chemicals such as benzene, smoking, genetic disorders, blood disorders, advancement in age, and others. Although novel strategies to manage AML, including a refinement of the conventional chemotherapy regimens, hypomethylating agents, and molecular targeted drugs, have been developed in recent years, resistance and relapse remain the main clinical problems. In this study, three databases, PubMed/MEDLINE, ScienceDirect, and Google Scholar, were systematically searched to identify various bioactive compounds with antileukemic properties. A total of 518 articles were identified, out of which 59 were viewed as eligible for the current report. From the data extracted, over 60 bioactive compounds were identified and divided into five major groups: flavonoids, alkaloids, organosulfur compounds, terpenes, and terpenoids, and other known and emerging bioactive compounds. The mechanism of actions of the analyzed individual bioactive molecules differs remarkably and includes disrupting chromatin structure, upregulating the synthesis of certain DNA repair proteins, inducing cell cycle arrest and apoptosis, and inhibiting/regulating Hsp90 activities, DNA methyltransferase 1, and histone deacetylase 1.

Wnt/ß-catenin signaling pathway inhibitors, glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside-1, diosmin, and rutin in medicinal plants have better binding affinities and anticancer properties: Molecular docking and ADMET study.

Wnt/ß-catenin signaling pathway plays a role in cancer development, organogenesis, and embryogenesis. The abnormal activation promotes cancer stem cell renewal, proliferation, and differentiation. In the present study, molecular docking simulation and ADMET studies were carried out on selected bioactive compounds in search of ß-catenin protein inhibitors for drug discovery against cancer. Blind docking simulation was performed using PyRx software on Autodock Vina. ß-catenin protein (PDB ID: 1jdh) and 313 bioactive compounds (from PubChem database) with selected standard anticancer drugs were used for molecular docking. The ADMET properties of the best-performing compounds were calculated using SwissADME and pkCMS web servers. The results obtained from the molecular docking study showed that glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside-1, diosmin, and rutin had the best binding interactions with ß-catenin protein based on their binding affinities. Glycyrrhizic acid and solanine had the same and lowest binding energy of -8.5 kcal/mol. This was followed by polyphyllin I with -8.4 kcal/mol, and crocin, hypericin, and tubeimoside-1 which all had a binding energy of 8.1 kcal/mol. Other top-performing compounds include diosmin and rutin with binding energy of -8.0 kcal/mol. The ADMET study revealed that the following compounds glycyrrhizic acid, solanine, polyphyllin I, crocin, hypericin, tubeimoside-1, diosmin, rutin, and baicalin all violated Lipinski's rule of 5 which implies poor oral bioavailability. However, based on the binding energy score, it was suggested that these pharmacologically active compounds are potential molecules to be tested against cancer.

Ameliorative Effect of Rice Husk Methanol Extract on Liver and Kidney Toxicities Induced by Subchronic Codeine Administration.

Background and Objective. Rice husk remains a key by-product of rice milling generated in significant amount. Accumulated evidence indicates that rice husk contains numerous bioactive compounds; however, its application is limited. This study was designed to introduce an in vivo application of rice husk extract, against opioid-induced liver and kidney injuries. Codeine was considered a psychotic inducer in this study due to its global alarming misuse recently. The hepatorenal ameliorative proclivity of rice husk extract against codeine-induced toxicity on the liver and kidney in male albino Wistar rats was examined. To this effect, thirty-six (36) albino Wistar rats of weight 100-110 g were utilized and weight-matched animals placed in 6 groups of 6 rats each. After 30 days of the combined administration of codeine and the rice husk extract, the experimental animals were assayed for basic liver and renal markers such as AST, ALP, ALT, total protein, albumin, conjugated and total bilirubin, urea, creatinine, and electrolytes (sodium, potassium, chloride, and bicarbonate). Rice husks were collected from a local rice mill, and the extraction was done with methanol. Findings. Rice husk extract (RHE) significantly ameliorated the recorded hepatic damage. More so, the extract showed a significant action on the renal markers as well. A histopathology examination of the liver and kidney tissues revealed that RHE showed a hepatorenal ameliorative potential in a dose-dependent manner. Conclusion. Phytonutrient from RH possesses a healing ability against opioid-induced hepatorenal toxicity. Thus, RH is safe for human and may be adopted to obviate and manage codeine-induced hepatorenal damage or injury. Significance and Novelty. Data on the application of RHE as a phytonutrient to combat liver and kidney injuries were demonstrated. Future studies should evaluate its potential on other organs.

FMS-like tyrosine kinase-3 (FLT3) inhibitors with better binding affinity and ADMET properties than sorafenib and gilteritinib against acute myeloid leukemia: in silico studies.

Over 30-35% of patients down with AML are caused by mutations of FLT3-ITD and FLT3-TKD which keeps the protein activated while it activates other signaling proteins downstream that are involved in cell proliferation, differentiation, and survival. As drug targets, many inhibitors are already in clinical practice. Unfortunately, the average overall survival rate for patients on medication suffering from AML is 5 years despite the huge efforts in this field. To perform docking simulation and ADMET studies on selected phytochemicals against FLT3 protein receptor for drug discovery against FLT3 induced AML, molecular docking simulation was performed using human FLT3 protein target (PDB ID: 6JQR) and 313 phytochemicals with standard anticancer drugs (Sorafenib and Gilteritinib in addition to other anticancer drugs). The crystal structure of the protein was downloaded from the protein data bank and prepared using Biovia Discovery Studio. The chemical structures of the phytochemicals were downloaded from the NCBI PubChem database and prepared using Open Babel and VConf softwares. Molecular docking was performed using PyRx on Autodock Vina. The ADMET properties of the best performing compounds were calculated using SwissADME and pkCMS web servers. The results obtained showed that glabridin, ellipticine and derivatives (elliptinium and 9-methoxyellipticine), mezerein, ursolic acid, formononetin, cycloartocarpesin, hypericin, silymarin, and indirubin are the best performing compounds better than sorafenib and gilteritinib based on their binding affinities. The top-performing compounds which had better binding and ADMET properties than sorafenib and gilteritinib could serve as scaffolds or leads for new drug discovery against FLT3 induced AML.Communicated by Ramaswamy H. Sarma.

The protective effect of fluted pumpkin seeds against atrazine-induced testicular injury.

The present study evaluated the protective effect of fluted pumpkin seeds (FPS) on atrazine (ATZ)-induced testicular damage. Twenty adult male Wistar rats were divided into four groups of five animals each. The control animals (Group A) received corn oil (2 mL/kg body weight), Group B animals received 50 mg ATZ/kg body weight by gavage, while Groups C and D received 50 mg ATZ/kg body weight once a week in addition to the gavage of 25 mg FPS/kg body weight and 50 mg FPS/kg body weight respectively for 60 days. The results showed that testicular myeloperoxidase activity and nitrite concentration were decreased in all groups compared to the control value. The increase in malondialdehyde and decrease in glutathione concentrations in group B were abrogated in group C (p < 0.05) but not in group D animals. The increase in γ-glutamyl transpeptidase and decrease in lactate dehydrogenase enzyme activities in the group B animals were also normalized to control values in group C but not in group D animals. Interestingly, the testis of the group D animals showed massive depletion of germ cells and the diameter of the seminiferous tubules of these animals were decreased compared to all other groups. However, the number of motile sperms, abnormal sperms and sperm count in Group D animals were similar to the ATZ-treated animals and lower than control values. In conclusion, FPS protected against ATZ-induced testicular damage but can also harm the testis at a higher dose.

Toxicity of Nanoparticles in Biomedical Application: Nanotoxicology.

Nanoparticles are of great importance in development and research because of their application in industries and biomedicine. The development of nanoparticles requires proper knowledge of their fabrication, interaction, release, distribution, target, compatibility, and functions. This review presents a comprehensive update on nanoparticles' toxic effects, the factors underlying their toxicity, and the mechanisms by which toxicity is induced. Recent studies have found that nanoparticles may cause serious health effects when exposed to the body through ingestion, inhalation, and skin contact without caution. The extent to which toxicity is induced depends on some properties, including the nature and size of the nanoparticle, the surface area, shape, aspect ratio, surface coating, crystallinity, dissolution, and agglomeration. In all, the general mechanisms by which it causes toxicity lie on its capability to initiate the formation of reactive species, cytotoxicity, genotoxicity, and neurotoxicity, among others.

Effect of aqueous extract of the leaves of Acalypha wilkesiana 'Godseffiana' Muell Arg (Euphorbiaceae) on the hematology, plasma biochemistry and ocular indices of oxidative stress in alloxan induced diabetic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Acalypha wilkesiana are used in Southern Nigeria for the management of hypertension and diabetes mellitus. In this study, the effect of aqueous extract of the leaves of Acalypha wilkesiana on the hematology, plasma biochemistry and ocular indices of oxidative stress was investigated in alloxan induced diabetic rats. METHODOLOGY: Diabetes mellitus was induced by injection of alloxan (80 mg/kg body weight), via the tail vein. The extract was administered orally at 100, 200 and 300 mg/kg (both to normal and diabetic rats), and metformin at 50mg/kg. RESULTS: On gas chromatographic analysis of the extract, twenty nine known flavonoids were detected, consisting mainly of 29.77% apigenin, 14.97% quercetin, 11.12% naringenin, 10.62% kaempferol, 9.05% (-)-epicatechin and 4.04% (+)-catechin. Tannic acid and ß-sitosterol were also detected. Compared to test control, the treatment lowered (significantly, P < 0.05) plasma glucose, triglyceride, conjugated bilirubin levels, atherogenic index of plasma, plasma alanine transaminase activity, total protein and total bilirubin, aspartate transaminase activity and unconjugated bilirubin, plasma urea, blood urea nitrogen and ocular malondialdehyde contents, lymphocyte and monocyte counts, and not significantly, plasma very low density lipoprotein cholesterol, but increased (significantly, P < 0.05) plasma calcium contents, total white cell and platelet counts, mean cell volume and ocular ascorbic acid content, and (though not significantly) plasma high density lipoprotein cholesterol level, red cell and neutrophil counts. CONCLUSIONS: This study showed that the extract was hypoglycemic, positively affected the hemopoietic system and integrity and function (dose dependently) of the liver and kidney of the diabetic rats; improved the lipid profile and had no deleterious effect on red cell morphology. It also protected against oxidative stress in ocular tissues. This study also revealed the presence of pharmacologically active compounds in the leaf extract. All of these highlights the cardioprotective potential of the leaves of Acalypha wilkesiana and support its use in traditional health practices for the management of diabetes mellitus.

Evaluation and decontamination of crude oil-polluted soils using Centrosema pubescen Benth and amendment-support options.

Growth performance and phytoremediation of soil of the Niger Delta Region of Nigeria artificially-contaminated with crude oil (up to 100 mL/2 kg soil) using centrosema pubescen Benth was investigated for 12 weeks. The soil samples in which the plants were established were either un-amended, or amended with NPK, or UREA or chicken manure. The extents of removal of PAHs and BTEX were measured as well as the rates of growth of the plants. Gas Chromatographic analysis confirmed the degradation of carcinogenic hydrocarbons like BTEXs and PAHs with this technique. At the highest dose of crude, the contaminant concentrations were 43 mg/kg PAHs, 10 mg/kg BTEX, and 5,613 mg/kg O&G. The greatest percent removal of BTEX was observed at the highest contaminant dose, and with the manure amendment. Similar trends were observed with PAHs and although they were less marked, the trends with PAHs may have been more highly statistically significant. There was no measurable plant uptake of contaminants. Inhibition of plant growth (measured as leaf area, shoot length and production of dry weight) was proportional to the dose of crude oil, but the manure amendment was very effective at reducing the growth inhibition. Interestingly, manure amendment reduced the phytotoxicity significantly in this study.

Hepatoprotective effect of an aqueous extract of the leaves of Acalypha wilkesiana 'Godseffiana' Muell Arg (Euphorbiaceae) against carbon tetrachloride induced liver injury in rats.

The potential of aqueous extract of the leaves of Acalypha wilkesiana, to protect against carbon tetrachloride induced liver damage was investigated in Wistar albino rats. The carbon tetrachloride was prepared 1:5 (v:v) in olive oil, and administered subcutaneously at 1 mL/kg body weight. The extract was administered to both normal and carbon tetrachloride treated rats at 100, 200 and 300 mg/kg. On fractionation and gas chromatographic analysis of the crude aqueous extract, thirty nine known alkaloids were detected, consisting mainly of akuamidine (69.027 %), voacangine (26.226 %), echitamine (1.974 %), echitamidine (0.599 %), lupanine (0.521 %) and augustamine (0.278 %). Compared to test control, the treatment dose dependently produced significantly lower (P<0.05) alkaline phosphatase, aspartate and alanine transaminase activities. Histopathological studies on the liver sections showed that pre-treatment with the extract protected against carbon tetrachloride induced fatty degeneration of hepatocytes, thus, confirming the results of the biochemical studies. The above results imply that treatment with the plant extract protects the liver against carbon tetrachloride induced hepatotoxicity, therefore, justifying the use of Acalypha wilkesiana in African traditional health care for the management of liver problems.

Characterization and safety evaluation of the impact of hydrocarbon contaminants on ecological receptors.

Hydrocarbon-contaminant removal efficiency of Bambara groundnuts and biomagnification was investigated. The crude oil contaminated soil samples in which the plants were established were either un-amended, or amended with NPK, or Urea, or Poultry manure. Amendments improved phytoextraction rates as follows: Urea - 63.37%, NPK - 65.99%, Poultry - manure - 70.04%, for PAH; Urea - 78.80%, NPK - 79.80%, Poultry manure - 87.90%, for BTEX. Hazard characterization from 28-day feeding study revealed negative effects of potentially toxic BTEX and PAH on organ weight, optimum digestibility and animal growth rate. Sleep time decreased with increasing hydrocarbon concentrations probably due to increased liver enzyme activity.

Hepatoprotective effects of methanolic extract and fractions of African mistletoe Tapinanthus bangwensis (Engl. & K. Krause) from Nigeria.

Methanolic extract and fractions, ethylacetate (EtF) and butanol (BuF) of leaves of African mistletoe (Tapinanthus bangwensis, Engl. & K. Krause) were evaluated for their hepatoprotective potential using CCl4-induced hepatotoxicity in Wistar albino rats. The activities of the marker enzymes alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP) and bilirubin were highest in rats treated with CCl4 alone. Oral administration at a fixed dose of 400 mg/kg body weight (BW) of the extract and fractions of T. bangwensis for seven days significantly (p ≤ 0.05) decreased the activity of marker enzymes and bilirubin. Total protein concentration increased significantly (p ≤ 0.05). These extracts also decreased the concentration of thiobarbituric acid reactive substances (TBARS) which indicated a reduction in lipid peroxidation. Histopathological examination of hepatocytes of rats administered methanolic extract (MeE) and fractions (EtF and BuF) showed normal architecture whereas rats treated with CCl4 alone was characterized by necrosis of the liver. Generally, among the three extracts, the BuF and EtF showed more hepatoprotective effect. The crude methanolic extract did not show any mortality up to a dose of 2000 g/kg BW. These findings suggest that T. bangwensis possesses strong antioxidant properties and hepatoprotective potentials against CCl4-induced hepatotoxicity in rats.

Inorganic ion levels of soils and streams in some areas of Ogoniland, Nigeria as affected by crude oil spillage.

The inorganic ion concentrations of soils and streams in the three locations (Yorla, Zaakpon and Goi) in Ogoniland, Nigeria affected by crude oil spillage were investigated. In general, inorganic ion concentrations of polluted soils and streams varied significantly (p = 0.05) from those of unpolluted soils and streams. Anions such as nitrate (NO(-)3), sulphate (SO(2-)4) and chloride (Cl-) showed significantly (p = 0.05) higher values in the polluted soils and steams than in the unpolluted controls. The phosphate (PO(3-)4) values were lower in the polluted soils and streams than in the unpolluted controls. PO(3-)4, NO(-)3, SO(2-)4 and Cl- concentrations were generally significantly (p = 0.05) higher in soils and streams from Yorla, Zaakpon and their control than in Goi North, Goi South and Goi control. Exchangeable cations and trace metal concentrations were significantly (p = 0.05) higher in the polluted soils and streams than in the unpolluted controls. Yorla and Zaakpon polluted soils and streams had higher concentrations of the exchangeable cations and trace metals compared to values from Goi, except for Na. Results also showed significantly higher values of heavy metals (Pb, Cd, Cr and Ni) in the polluted soils compared to their controls, and values were also significantly (p = 0.05) higher in Yorla, Zaakpon and their control compared to Goi North, Goi South and Goi control. Values obtained in polluted streams were higher than in the unpolluted though not significant at the 5% level (p = 0.05). The anionic and cationic concentrations of Yorla and Zaakpon soils and streams were generally higher than those of Goi, indicating that Yorla and Zaakpon areas were more polluted than Goi. Although the concentrations of most of the anions and cations analysed in the polluted soils and streams were within the World Health Organisation's permissible values for the protection of humans and environment, the streams of Yorla, Zaakpon and Goi are in general being polluted with inorganic ions. This may make these soils and streams unacceptable for domestic and industrial uses if not treated, and soils (farmlands) may also become unsuitable for agricultural purposes.

Effect of heat treatment on the proximate composition, energy values, and levels of some toxicants in African yam bean (Sphenostylis stenocarpa) seed varieties.

The effects of heat treatments on the proximate composition, energy content, and levels of some antinutritional factors in brown and marble-colored African yam bean (AYB) seed flours were investigated. In raw brown and marble-colored AYB seed flours; moisture content, dry matter, crude protein, crude fat, ash, total carbohydrate and caloric value did not differ significantly at the 5% level. Autoclaving and cooking slightly increased the moisture level. Crude protein, crude fat, and ash contents were decreased by autoclaving and were further decreased by cooking. The decrease was not, however, considerable for the AYB that is not eaten raw and whose full nutritional potential as a legume can be derived only when heat treated, as previous reports have indicated for legume seeds. The levels of the toxicants were generally higher in the raw brown AYB compared to the marble-colored, and were generally reduced by both autoclaving and cooking. In the most commonly available and consumed marble-colored AYB, autoclaving at 121 degrees C, 15 psi for 20 min decreased cyanogenic glycosides by 46%, oxalate by 48.9%, tannin by 15.0%, saponin by 14.8% and trypsin inhibitors by 61.3% while cooking for 3.5 hours in tap water decreased these toxic factors by 66.5%, 70.3%, 72.2%, 48.7%, and 86.0%, respectively. The results indicate that for raw samples, varietal difference did not significantly affect nutrient composition though the toxicants were generally higher in the brown AYB than the marble-colored. Autoclaving decreased both nutrient value and the level of toxicants in the two seed types; values were further reduced by cooking. Of the toxicants, trypsin inhibitor was found to be the most heat-labile and of the heat treatment methods, cooking to tenderness is recommendable.