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.

Ficus exasperata Attenuates Acetaminophen-Induced Hepatic Damage via NF-κB Signaling Mechanism in Experimental Rat Model.

Ficus exasperata has been used to treat ulcer, diabetes, fever, and a variety of stress-related disorders. Acetaminophen (APAP) overdose is the most common cause of drug-induced acute liver injury. In this study, we evaluated the hepatoprotective effect and antioxidant capacity of ethanolic extract of F. exasperata (EFE) on acetaminophen-induced hepatotoxicity in albino rats. Rats were pretreated with EFE (150, 250, 500 mg/kg) and thereafter received 250 mg/kg APA intraperitoneally (i.p.). The normal control group received distilled water, while the negative control group received 250 mg/kg APAP, respectively. Hepatotoxicity and oxidative stress-antioxidant parameters were then assessed. Flavonoids, saponins, steroids, and glycosides, but not phenolics were detected by EFE phytochemical analysis. No mortality was recorded on acute exposure of rats to varying concentrations of APAP after 24 h; however, a dose-dependent increase in severity of convulsion, urination, and hyperactivity was observed. APAP overdose induced high AST, ALT, ALP, and total bilirubin levels in the serum, invoked lipid peroxidation, depleted GSH, decreased CAT, SOD, and GST levels, respectively. Nitric oxide (NO) level, myeloperoxidase activity, TNF-α, IL-1ß, NF-κB, COX-2, MCP-1, and IL-6 were also increased. Importantly, pretreatment of rats with EFE before acetaminophen ameliorated and restored cellular antioxidant status to levels comparable to the control group. Our results show and suggest the hepatoprotective effect of F. exasperata and its ability to modulate cellular antioxidant status supports its use in traditional medicine and renders it safe in treating an oxidative stress-induced hepatic injury.

Pharmaceutical and personal care products as emerging environmental contaminants in Nigeria: A systematic review.

The increasingly broad and massive use of pharmaceuticals (human, veterinary) and personal care products in industrially developing nations makes their uncontrolled environmental and ecological impact a true concern. Focusing on Nigeria, this systematic literature search (databases: PubMed, ScienceDirect, Google Scholar, EMBASE, Scopus, Cochrane library and African Journals Online) aims to increase visibility to the issue. Among 275 articles identified, 7 were included in this systematic review. Studies indicated the presence of 11 personal care products (15.94 %) and 58 pharmaceutical products (84.06 %) in surface and ground water, leachates, runoffs, sludge, and sediments. The 42.86% (3/7) of reviewed studies reported 17 analgesics; 71.42 % (5/7) reported 16 antibiotics; 28.57 % (2/7) reported 5 lipid lowering drugs; 28.57% reported anti-malaria and fungal drugs; 14.29 % (1/7) reported estrogen drugs. Different studies report on sunscreen products, hormone, phytosterol, insect repellent, and ß1 receptor. Gemfibrozil (<4-730 ng/L), Triclosan (55.1-297.7 ng/L), Triclocarban (35.6-232.4 ng/L), Trimethoprim (<1-388 ng/L) and Tramadol (<2-883 ng/L) had the highest range of concentrations. Findings confirm the need of i) legislation for environmental monitoring, including biota, ii) toxicological profiling of new market products, and iii) sensitization on appropriate use and disposal of pharmaceuticals and personal care products.

Selenium abates manganese-induced striatal and hippocampal toxicity via abrogation of neurobehavioral deficits, biometal accumulation, oxidative stress, inflammation, and caspase-3 activation in rats.

Excessive exposure to manganese (Mn) is associated with neurotoxicity characterized by oxidative stress, inflammation, and apoptosis induction. Selenium (Se) has been shown to possess antioxidant, anti-inflammatory, and anti-apoptotic properties in humans and animals. The present study investigated the neuroprotective mechanism of Se in rats sub-chronically treated with Mn at 30 mg/kg body weight or orally co-treated with Se at 0.2 and 0.4 mg/kg body weight for 35 consecutive days. Locomotive and exploratory profiles were recorded and computed with the aid of ANY-Maze (a video-tracking software) for 5-min trial, in a novel apparatus. The ANY-Maze analysis showed that Se significantly (p < 0.05) abated Mn-induced locomotive impairment evidenced by increased in maximum speed, total time traveled, absolute turn angle, number of line crossing, rotation and forelimb grip and decreased total time immobile, grooming, and negative geotaxis as verified by the enhanced track plot density. Furthermore, the striatum and hippocampus of the rats were excised and the levels of Mn and Se, oxidative stress markers, proinflammatory cytokines including acetylcholinesterase and caspase-3 activities were assayed. The result shows that Se abates Mn-mediated accumulation of Mn. Also, Se ameliorated Mn-induced decrease in antioxidant enzymes as well as glutathione level and increase in acetylcholinesterase activity, lipid peroxidation, proinflammatory cytokines (i.e., interleukin (IL)-6, IL-1ß, tumor necrosis factor alpha), and caspase-3 activation in the striatum and hippocampus of the rats. Collectively, Se abated Mn-induced striatal and hippocampal toxicity via abrogation of neurobehavioral deficits, biometal accumulation, oxidative stress, inflammation, and caspase-3 activation in rats. Se may serve as a neuroprotective agent against Mn-mediated neurotoxicity.

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.

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.

Bioactive Compounds Effective Against Type 2 Diabetes Mellitus: A Systematic Review.

BACKGROUND: Type 2 diabetes (adult onset diabetes) is the most common type of diabetes, accounting for around 90% of all diabetes cases with insulin resistance and insulin secretion defect. The key goal of anti-diabetic therapy is to increase the development of insulin, immunity and/or decrease the amount of blood glucose. While many synthetic compounds have been produced as antidiabetic agents, due to their side effects and limited effectiveness, their usefulness has been hindered. METHODS: This systematic review investigated the bioactive compounds reported to possess activities against type 2 diabetes. Three (3) databases, PubMed, ScienceDirect and Google Scholar were searched for research articles published between January 2010 and October 2020. A total of 6464 articles were identified out of which 84 articles were identified to be elligible for the study. RESULT AND DISCUSSION: From the data extracted, it was found that quercetin, Kaempferol, Rosmarinic acid, Cyanidin, Rutin, Catechin, Luteolin and Ellagic acid were the most cited bioactive compounds which all falls within the class of polyphenolic compounds. The major sources of these bioactive compounds includes citrus fruits, grapes, onions, berries, cherries, broccoli, honey, apples, green tea, Ginkgo biloba, St. John's wort, green beans, cucumber, spinach, tea, Rosmarinus officinalis, Aloe vera, Moringa oleifera, tomatoes, potatoes, oregano, lemon balm, thyme, peppermint, Ocimum basilicum, red cabbage, pears, olive oil and walnut.

Emerging pollutants in Nigeria: A systematic review.

Emerging pollutants represent a group of synthetic or naturally occurring compounds that are not normally monitored within the environment but can enter into the environment and cause different adverse ecological and health effects. This systematic review identified the various emerging pollutants in Nigeria. The following databases, ScienceDirect, PubMed, Google Scholar, and African Journals OnLine (AJOL) were searched to identify studies on pollutants of emerging concerns in Nigeria. A total of 933 articles were identified out of which 30 articles were selected to be eligible for the study. Over 250 emerging pollutants were identified and divided into 9 major groups which are personal care products, pharmaceuticals, industrial chemicals, polycyclic aromatic hydrocarbons, volatile organic compounds, pesticides, mycotoxins, radionuclides and electromagnetic radiations (Gamma radiation) and other pollutants of emerging concerns such as microbes, microplastics, and particulate matter. These pollutants are found in water bodies and underground waters, soils and sediments, biological systems, and ambient air at different concentrations with seasonal variations. Some of these pollutants act as endocrine disruptors, ß-adrenergic receptors agonist blockers, oxidative stress inducers and can cause genetic alterations in DNA and epigenetic reprogramming through global DNA methylation, gene-specific CpG methylation and microRNA expression. Emerging pollutants of public health concern in Nigeria are on the increase and are threat to both ecological and human health.

Plant-Derived Food Grade Substances (PDFGS) Active Against Respiratory Viruses: A Systematic Review of Non-clinical Studies.

Human diet comprises several classes of phytochemicals some of which are potentially active against human pathogenic viruses. This study examined available evidence that identifies existing food plants or constituents of edible foods that have been reported to inhibit viral pathogenesis of the human respiratory tract. SCOPUS and PUBMED databases were searched with keywords designed to retrieve articles that investigated the effect of plant-derived food grade substances (PDFGS) on the activities of human pathogenic viruses. Eligible studies for this review were those done on viruses that infect the human respiratory tract. Forty six (46) studies met the specified inclusion criteria from the initial 5,734 hits. The selected studies investigated the effects of different PDFGS on the infectivity, proliferation and cytotoxicity of different respiratory viruses including influenza A virus (IAV), influenza B virus (IBV), Respiratory syncytial virus (RSV), human parainfluenza virus (hPIV), Human coronavirus NL63 (HCoV-NL63), and rhinovirus (RV) in cell lines and mouse models. This review reveals that PDFGS inhibits different stages of the pathological pathways of respiratory viruses including cell entry, replication, viral release and viral-induced dysregulation of cellular homeostasis and functions. These alterations eventually lead to the reduction of virus titer, viral-induced cellular damages and improved survival of host cells. Major food constituents active against respiratory viruses include flavonoids, phenolic acids, tannins, lectins, vitamin D, curcumin, and plant glycosides such as glycyrrhizin, acteoside, geniposide, and iridoid glycosides. Herbal teas such as guava tea, green and black tea, adlay tea, cistanche tea, kuding tea, licorice extracts, and edible bird nest extracts were also effective against respiratory viruses in vitro. The authors of this review recommend an increased consumption of foods rich in these PDFGS including legumes, fruits (e.g berries, citrus), tea, fatty fish and curcumin amongst human populations with high prevalence of respiratory viral infections in order to prevent, manage and/or reduce the severity of respiratory virus infections.

Toxicity Effect of Sub-Chronic Oral Administration of Class Bitters® - A Polyherbal Formula on Serum Electrolytes and Hematological Indices in Male Wistar Albino Rats.

The indiscriminate administration of ready-to-use herbal formulations has become a major concern due to their potential health risk. The study investigated the effect of class bitters® (CB) - a polyherbal formula prepared with Mondia whitei, Khaya senegalensis, Capparis erythrocarpus, Thoningia sanguinea and Xylopia aethiopica on serum electrolytes and hematological parameters in male Wistar albino rats. Two doses (500 and 1000 mg kg-1) of the polyherbal drugs were administered orally to male Wistar albino rats for a period of 9 weeks. The results showed that administration of 500 and 1000 mg kg-1 body weight of CB recorded a marked increase in the levels of sodium and chlorum when compared with control. However, there was a marked reduction in the levels of potassium and hydrogen carbonate. The results of the study also showed a significant (P≤0.05) decrease in the level of hematological parameters such as hemoglobin (Hb), packed cell volume (PCV), red blood cells (RBCs) and platelets levels in the male Wistar albino rats, when compared with control. The marked decrease in Hb, PCV, RBCs and platelets concentrations observed in experimental rats in this study suggest that CB may have an adverse effect on erythropoiesis. These observations therefore showed that long-term administration of CB might cause renal disease and anemia.

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.