Toxicological Features Research Articles

Biological potential, chemical profiling, and molecular docking study of Morus alba L. extracts

Morus alba L. is a plant with a long history of dietary and medicinal uses. We hypothesized that M. alba possesses a significant biological potential. In that sense, we aimed to generate the chemical, antimicrobial, toxicological, and molecular profile of M. alba leaf and fruit extracts. Our results showed that extracts were rich in vitamin C, phenols, and flavonoids, with quercetin and pterostilbene concentrated in the leaf, while fisetin, hesperidin, resveratrol, and luteolin were detected in fruit. Extracts exhibited antimicrobial activity against all tested bacteria, including multidrug-resistant strains. The widest inhibition zones were in Staphylococcus aureus ATCC 33591. The values of the minimum inhibitory concentration ranged from 15.62 μg/ml in Enterococcus faecalis to 500 μg/ml in several bacteria. Minimum bactericidal concentration ranged from 31.25 μg/ml to 1000 μg/ml. Extracts impacted the biofilm formation in a concentration-dependent and species-specific manner. A significant difference in the frequency of nucleoplasmic bridges between the methanolic extract of fruit (0.5 μg/ml, 1 μg/ml, 2 μg/ml), as well as for the frequency of micronuclei between ethanolic extract of leaf (2 μg/ml) and the control group was observed. Molecular docking suggested that hesperidin possesses the highest binding affinity for multidrug efflux transporter AcrB and acyl-PBP2a from MRSA, as well as for the SARS-CoV-2 Mpro. This study, by complementing previous research in this field, gives new insights that could be of great value in obtaining a more comprehensive picture of the Morus alba L. bioactive potential, chemical composition, antimicrobial and toxicological features, as well as molecular profile.

Comprehensive study on pharmacognostic, pharmacological, and toxicological features of Ficus racemosa in Alzheimer's disease using GC-MS and molecular docking analyses.

Alzheimer's disease (AD) presents as a widespread neurodegenerative condition impacting over 55 million individuals globally, with an annual rise of 10 million new cases. Despite its staggering prevalence, the absence of a definitive cure establishes the need for a revisit. We explore the alternative strategies, focusing on the potential therapeutic efficacy of ethanolic extracts derived from the fruit and leaf of Ficus racemosa Linn. The investigation comprehensively explores pharmacognostic, phytochemical, toxicological, and pharmacological characteristics. In addition to pharmacognostic and physicochemical analyses, toxicological evaluations conducted on experimental animals demonstrated the innocuous nature of the ethanolic extracts (from both fruit and leaf) of F. racemosa, as evidenced by assessments of hemocompatibility, oxidative parameters, and vital organ histology. Phytochemical profiling via GC-MS identified 48 and 80 phytoconstituents in the fruit and leaf extracts, respectively. These constituents were screened for bioactive potential using the "Lipinski Rule of Five," resulting in the selection of 25 and 33 constituents from fruit and leaf extracts, respectively. Subsequent molecular docking studies against the AChE enzyme revealed promising interactions of the selected phytoconstituents. Furthermore, the top-scoring phytoconstituents were subjected to in silico screening to assess their interactions with β- and γ-secretase enzymes, in addition to the AChE enzyme. The cumulative findings substantiate the therapeutic utility of the plant extracts, particularly in the context of AD. In conclusion, our investigation highlights the promising therapeutic potential of selected phytoconstituents derived from ethanolic extracts of F. racemosa in mitigating AD pathology by targeting key enzyme sites such as AChE, β-, and γ-secretase.

Berberine modulates cardiovascular diseases as a multitarget-mediated alkaloid with insights into its downstream signals using in silico prospective screening approaches

Atherosclerosis is potentially correlated with several cardiac disorders that are greatly associated with cellular oxidative stress generation, inflammation, endothelial cells dysfunction, and many cardiovascular complications. Berberine is a natural isoquinoline alkaloid compound that widely modulates pathogenesis of atherosclerosis through its different curative potentials. This in silico screening study was designed to confirm the potent restorative properties of berberine chloride as a multitarget-mediated alkaloid against the CVDs and their complications through screening, identifying, visualizing, and evaluating its binding models, affinities, and interactions toward several CVDs-related targets as direct and/or indirect-mediated signals via inhibiting cellular ER stress and apoptotic signals and activating autophagy pathway. The drug-likeness properties of berberine were predicted using the computational QSAR/ADMET and Lipinski’s RO5 analyses as well as in silico molecular docking simulations. The potent berberine-binding modes, residues-interaction patterns, and free energies of binding scores towards several CVDs-related targets were estimated using molecular docking tools. Furthermore, the pharmacokinetic properties and toxicological features of berberine were clearly determined. According to this in silico virtual screening study, berberine chloride could restore cardiac function and improve pathogenic features of atherosclerotic CVDs through alleviating ER stress and apoptotic signals, activating autophagy, improving insulin sensitivity, decreasing hyperglycemia and dyslipidemia, increasing intracellular RCT signaling, attenuating oxidative stress and vascular inflammation, and upregulating cellular antioxidant defenses in many cardiovascular tissues. In this in silico study, berberine chloride greatly modulated several potent CVDs-related targets, including SIGMAR1, GRP78, CASP3, BECN1, PIK3C3, SQSTM1/p62, LC3B, GLUT3, INSR, LDLR, LXRα, PPARγ, IL1β, IFNγ, iNOS, COX-2, MCP-1, IL10, GPx1, and SOD3.

Innovations in measuring and mitigating phytohemagglutinins, a key food safety concern in beans

Abstract Phytohemagglutinin (PHA) is a seed storage protein and a type of lectin originally discovered in the common bean (Phaseolus vulgaris) for its blood-agglutinating effect. Due to its interactions with gut epithelia and digestive enzymes and its potential to trigger allergic reactions, PHA can lead to various symptoms in the human body. As a result, it has been regarded as a significant antinutritional factor in beans and other legumes. While several published works have summarized its structural, biochemical, and toxicological features, there is a scarcity of literature that reviews the detection, quantification, and reduction of PHA in beans, which is fundamental for the development of safer bean varieties. In this review, we present a comprehensive analysis of traditional and innovative bio-sensing methods for measuring PHA, including the recently available ultrapure liquid chromatography–tandem mass spectrometry and emerging aptamer sensor-based techniques, while discussing their respective advantages and disadvantages. We also revisit existing studies dedicated to creating PHA-depleted common bean varieties and explore the potential for reducing PHA content in beans without compromising their resistance to biotic stress. Additionally, we offer insights into the potential for controlling PHA content using the latest biotechnologies and breeding strategies. Overall, this review compiles rare and valuable information from studies that solely focuses on detection and depletion of PHA to shed light on and apply technological advancements in addressing potential food safety risks associated with the consumption of common beans.

An instrument-free photoluminescent sensor array based on “turn-off” bimetallic lanthanide metal–organic frameworks for antibiotic determination

The widespread use of antibiotics results in harmful residues, posing a serious threat to ecosystems and human health. Given synergetic or antagonistic toxicological features often exist among different antibiotics, it is vital to develop methods to synchronously determine these contaminants. Herein, we develop a hand-held photoluminescent sensor array based on “turn-off” bimetallic lanthanide metal–organic frameworks (MOFs) to realize the identification and quantification of six common antibiotics. Three Tb/Eu-MOFs with different bimetallic proportions were synthesized and employed to provide signals toward multiple antibiotics based on their differential contributions to the photoluminescence quenching of these probes. By designing a 3D-printed smartphone-equipped signal capturing platform, tiny luminescence variations induced by different antibiotics were recorded and processed for the classification and identification of these targets via pattern recognition analysis. Compared to conventional sensor arrays requiring cumbersome signal reading instruments and complex sensing units, our platform really enables instrument-free in-field detection of multiple targets with only a basic material. The platform could identify not only single antibiotics in a wide level scope but also various combinations of two, three or even four antibiotics with good discrimination capacity. Differentiation of multiple antibiotics in river water, milk, and urine matrices was also demonstrated. Furthermore, over 90% accuracy was gained for unknown samples in double-blind tests. Our work offers a portable, low-cost, and high-performance tool to determine multiple antibiotics simultaneously, which will stimulate future exploration of hand-held sensor arrays with simple sensing elements for on-site analysis and point-of-care diagnosis.

Ecological and toxicological features of the effect of stable cesium on striated muscle tissue (myocardium and skeletal muscles) of mammals

Recently, the risks of radiation danger have significantly increased. This is connected with the start of a full-scale war against Ukraine and the seizure of the Zaporizhzhya NPP by the Russian Federation, which has the second most powerful arsenal of nuclear weapons in the world. The majority of studies devoted to the effect of radioactive radiation on the human body and animals absolutely do not take into account the ecotoxic effect of the carrier and a chemical element. At the same time, the body does not distinguish between radioactive and non-radioactive isotopes of chemical elements and interacts with them during exchange processes. The aim of the work was to study the influence of stable cesium on the microscopic structure of striated muscle tissue, both skeletal and cardiac ones. The results of our research revealed that intensive accumulation of cesium for 24 days occurred in all the examined organs and tissues. In fact, the most intensive accumulative process appeared to be in the heart by 214.9 times and by 695.3 times with skeletal muscles, with a simultaneous decrease in potassium content by 19.2% and 29.1%, respectively, compared to intact rats. We can talk about the presence of two mechanisms of action of cesium on tissues, including striated muscles: as an antagonist of potassium, which concerns the transport system of the latter and as a toxic element that initiates peroxide processes with subsequent modification of membranes and their potassium channels. Functional disturbances in the work of potassium channels of excitable tissues in the repolarization phase occur in the conditions of an increase in intracellular cesium in striated muscles. These disorders can proceed according to the type of acquired "potassium" channelopathies, which in the myocardium can manifest in the form of rhythm disorders, prolonged QT syndrome, etc. This leads to the appearance of significant violations of the histological structure of the examined tissues. Cesium has pronounced damaging effects on both skeletal and cardiac striated muscle tissue, with morphological changes in skeletal and cardiac striated muscle tissue being generally similar. Dystrophic changes in the nuclei and cytoplasm of cardiomyocytes and striated muscles, signs of impaired blood circulation in the microcirculatory channel with the formation of vascular wall edema, destruction of endothelial cells, various types of hemorrhages and lymphohistiocytic infiltration of the stroma of fibers are the consequences of the toxic effect of cesium on tissues. Thus, the results of changes in the histological structure of striated muscles under the action of cesium chloride obtained by us indicate a fairly high cytocidal activity of stable cesium.

Whole-Transcriptome Analysis on the Leaves of Rosa chinensis Jacq. under Exposure to Polycyclic Aromatic Hydrocarbons.

The leaves of plants can be recommended as a cheap and sustainable environmental protection tool to mitigate PAHs with high toxicity in the ambient environment because they can serve as a reactor to remove ambient PAHs. Although previous studies have demonstrated that PAHs exhibit toxicological features, our knowledge about how ambient PAHs influence the leaves of plants is limited regarding the leaves of plants reducing ambient PAHs as a reactor. In this study, 1-year-old Rosa chinensis Jacq. with good growth potential was selected as a model plant. The leaves of Rosa chinensis Jacq. were exposed to 16 types of PAHs in the environmental concentration exposure group (0.1 μg L-1) and high-concentration exposure group (5 μg L-1) for seven days. In comparison, the leaves of Rosa chinensis Jacq. were exposed to de-ionized water and were chosen as the control group. During the exposure periods, the physiological parameters of leaves including, chlorophyll value, water content, temperature and nitrogen, were monitored using a chlorophyll meter. After 7 days of exposure, the leaves in the control and exposure groups were collected and used for whole-transcriptome analysis. Our results demonstrate that significant differentially expressed genes were observed in the leaves of Rosa chinensis Jacq. exposed to individual PAHs at 5 μg L-1 compared to the control group. These differentially expressed genes were involved in seven main pathways using bioinformatic analyses. In contrast, the levels of PAHs at environmentally relevant concentrations had negligible impacts on the physiological parameters and the gene transcription levels of the leaves of Rosa chinensis Jacq. Our results may provide direct evidence to remove ambient PAHs using terrestrial trees without considering the risk of PAHs at environmentally relevant concentrations on the leaves of terrestrial plants.

Protective Effects of Pelargonidin against DMBA-Induced Mammary Tumorigenesis in BALB/c Mice through Reduced Oxidative Stress and Lipid Anomalies

Among luminal types of breast cancers, ER + breast cancer is the most frequently diagnosed cancer globally. ER + breast cancer is commonly treated with SERM drugs that block ER to prevent ER-mediated cancerous growth. Our previous computational screening found pelargonidin (PG) can inhibit ER-signaling with potent bioactivity and satisfactory toxicological features. The present study explored the anti-tumoral prospect of PG against DMBA-induced ER + murine mammary carcinogenesis. The female BALB/c mice were divided into control (A) and DMBA-exposed groups. Following tumor appearance, the DMBA-exposed group was divided into five groups: tumor control, PG-treated (Groups P25, P50, and P100), and tamoxifen-treated (TAM). The results indicated that PG-treatment dose-dependently reduced the mean tumor volume, reinstated body weight loss, and enhanced the percentage survival of tumor-bearing mice. In addition, we recorded a significant reduction in LPO, total cholesterol, and triglycerides and a surge in the activity of antioxidases and phase II detoxifying enzymes in PG-treated animals. PG also dose-dependently increased the serum level of unbound estradiol, an indicator of competitive ER binding by an ER agonist/antagonist. These data suggest that pelargonidin has potent anticancer potential against the animal model of ER + breast cancer that matches the efficiency of tamoxifen with conceivably fewer side effects.

Molecular docking and dynamics simulation analysis of the human FXIIa with compounds from the Mcule database.

The human factor XIIa is a serine protease enzyme that is implicated in the pathological thrombosis. This coagulation factor represents an interesting molecular target to design safer antithrombotic agents without adversely influencing physiological hemostasis. Therefore, it is of interest to virtually screen the human factor XIIa crystal with millions of compounds in Mcule database in order to identify potential inhibitors. For this purpose, both molecular docking and dynamics simulation were employed to identify potential hits. Also, various predictive approaches were utilized to estimate chemical, pharmacokinetics and toxicological features for the top hits. As such, we report here that compound 4 (1-(4-benzylpiperazin-1-yl)-2-[5-(3,5-dimethylpyrazol-1-yl)-1,2,3, 4-tetrazol-2-yl]ethanone) may be a potential ligand against the human factor XIIa for further consideration in the design and development of novel antithrombotic agents.

Smart delivery systems for microbial biofilm therapy: Dissecting design, drug release and toxicological features.

Bacterial biofilms are highly protected surface attached communities of bacteria that typically cause chronic infections. To address their recalcitrance to antibiotics and minimise side effects of current therapies, smart drug carriers are being explored as promising platforms for antimicrobials. Herein, we briefly summarize recent efforts and considerations that have been applied in the design of these smart carriers. We guide readers on a journey on how they can leverage the inherent biofilm microenvironment, external stimuli, or combine both types of stimuli in a predictable manner. The specific carrier features that are responsible for their 'on-demand' properties are detailed and their impact on antibiofilm property are further discussed. Moreover, an analysis on the impact of such features on drug release profiles is provided. Since nanotechnology represents a significant slice of the drug delivery cake, some insights on the potential toxicity are also depicted. We hope that this review inspires researchers to use their knowledge and creativity to design responsive systems that can eradicate biofilm infections.

Development of the Sm14/GLA-SE Schistosomiasis Vaccine Candidate: An Open, Non-Placebo-Controlled, Standardized-Dose Immunization Phase Ib Clinical Trial Targeting Healthy Young Women.

We report the successful closure of Phase I clinical trials, comprising Phases Ia and Ib, of the vaccine candidate against human schistosomiasis: the Schistosoma mansoni 14 kDa fatty acid-binding protein (Sm14) + glucopyranosyl lipid A in squalene emulsion (GLA-SE). Shown here are the results of Phase Ib, an open, non-placebo-controlled, standardized-dose immunization trial involving 10 healthy 18–49-year-old women. Fifty micrograms of the Sm14 protein plus 10 µg GLA-SE per dose was given intramuscularly thrice at 30-day intervals. Participants were assessed clinically, biochemically, and immunologically for up to 120 days. In preambular experiments involving vaccinated pregnant female rabbits, we did not find any toxicological features in either the offspring or mothers, and the vaccine induced adaptive immunity in the animals. In women, no adverse events were observed, and vaccination induced high titers of anti-Sm14 serum IgG antibody production. Vaccination also elicited robust cytokine responses, with increased TNFα, IFNγ, and IL-2 profiles in all vaccinees on days 90 and 120. The completion of Phase I clinical trials, which were performed to the highest standards set by Good Clinical Research Practice (GCP) standards, and preclinical data in pregnant rabbits enabled the vaccine candidate to proceed to Phase II clinical trials in endemic areas.

Diabetes ethnopharmacology in rural region: study of a case report and review of literature

Recently, there is an ascendant recourse for medicinal plants’ utilization as treatment of several chronic diseases, including diabetes. While effective in wound healing, some herbs might present toxic effects at certain doses or when used for long periods. In this study, the frequently used antidiabetic herbs, in a rural region, was reviewed with special focus on their possible toxicological features

Morphological, spectral and toxicological features of new composite material of titanium nanodioxide with nanosilver for use in medicine and biology

The results of this study indicate that titanium dioxide nanoparticles (nano-TiO2) possess adsorptive, photocatalytic, bactericidal, virucidal and fungicidal properties, which are used in antibacterial coating, for air and water disinfection. In parallel with studies of the physicochemical characteristics of titanium dioxide, its toxicological assessment was carried out to prevent possible harmful effects on humans and the biosphere objects, followed by an assessment of the nano-TiO2 hazard class. To enhance these useful properties of nano-TiO2, nanopowders of titanium dioxide and a composite of titanium dioxide were synthesized with a silver (nano-TiO2 /Ag) by way of chemical precipitation of metatitanic acid adding silver nitrate to the composite at 500-600°C. It was stated that the synthesized nanostructures have the following characteristics: anatase crystal structure of TiO2 (anatase, rutile, brookite – natural crystalline modifications of TiO2), the size of Ag nanoparticles is 35-40 nm, TiO2 – 13-20 nm. Nanocomposite has surface defects of the crystal lattice (oxygen vacancies, impurities, excess electrons or holes), silver nanoparticles are localized on the surface of anatase TiO2, which increases adsorptive, photocatalytic, biological and specifically antibacterial properties of the composite material nano-TiO2/Ag. According to the parameters of acute intraperitoneal toxicity, the studied nanocomposite anatase nano-TiO2/Ag was classified as a moderately dangerous substance (material). Nano-TiO2 and TiO2/Ag nanocomposites do not cause local irritation to the skin, yet have a mildly irritating effect on the mucous membrane of the eye, and are also characterized by a weak sensitization effect.

A review on essential oil analyses and biological activities of the traditionally used medicinal plant Thymus vulgaris L

Since the old times, seeds producing plants have played a vital role in the progress of human culture to treat diseases. Medicinal plants are used traditionally by the local communities to treat diseases. Recently, a report has shown that more than 250,000 flowering plant species are available globally. Scientists are continuously working on higher plants to help and understand plant poisonousness and to defend humans and animals from natural toxins. A plant`s toxicity and its medical use are dependent on the plant’s volatile phytochemicals. Thymus vulgaris L is a common aromatic plant used widely as a folk medicine to treat various diseases by different ethnic communities around the globe including the Sultanate of Oman. Previous studies in Oman showed that the selected plant species contains several groups of phytochemicals such as essential oils and secondary metabolic compounds they can enhance their biological and toxicological activities. Therefore, the aim of the present review is to explore the volatile phytochemicals, biological and toxicological features of Thymus vulgaris grown in Oman. The results can be helpful for discovering new drugs to treat asthma, cough, chronic bronchitis and other infectious diseases. In conclusion, this review provides information on the volatile phytochemicals, pharmacological and toxicological aspects of the selected plant species.

Computational research of Belnacasan and new Caspase-1 inhibitor on cerebral ischemia reperfusion injury.

Cerebral ischemia-reperfusion injury is one of the most severe diseases in terms of mortality and disability, which seriously threatens human life and health. In clinical treatment, drug thrombolysis or mechanical interventional thrombolysis are used to quickly restore the blood supply of ischemic brain tissue. But with the rapid recovery of blood flow, complex pathophysiological processes such as oxidative stress and inflammation will further aggravate brain tissue damage, namely cerebral ischemia-reperfusion injury, for which there is no effective treatment. Recent studies have shown that the medical community has paid the role of inflammation and pyroptosis in cerebral ischemia-reperfusion injury more and more attention. And Caspase-1 was found to play a vital role in regulating inflammation pathways and pyroptosis in many inflammation-associated diseases, especially in cerebral ischemia-reperfusion injury. Not only that, Caspase-1 inhibitors have been shown to reduce the damage of cerebral ischemia-reperfusion injury by inhibiting inflammation and pyroptosis. And the Caspase-1 inhibitor, Belnacasan, has been proved to modify the active site of Caspase-1 and lead to the blocking of Caspase-1, thus correlating with tissue protection of inflammatory diseases in animal models. Therefore, it’s essential to screen and design potential Caspase-1 inhibitors to reduce cerebral ischemia-reperfusion injury and protect brain function by reducing inflammation and pyroptosis, which provides a new idea for clinical treatment of the cerebral ischemia-reperfusion injury. This study applied a group of computer-aided technology, such as Discovery Studio 4.5, Schrodinger, and PyMol, to screen and assess potential Caspase-1 inhibitors. Moreover, the ADME (absorption, distribution, metabolism, excretion) and TOPKAT (Toxicity Prediction by Computer Assisted Technology) molecules of Discovery Studio 4.5 were conducted to evaluate molecules' pharmacological and toxicological features. Then, precise molecular docking was applied to assess the binding mechanism and affinity between Caspase-1 and selected compounds. Besides, molecular dynamics simulations were performed to determine the stability of ligand-receptor complexes in the natural environment. In summary, this study lists promising drug candidates and their pharmacological properties, promoting the development of Caspase-1 inhibitors and deepening the understanding of the interaction between inhibitors and Caspase-1.

Indexes of tobacco smoke contribution to environmental particulates based on molecular fingerprints of alkanes.

Tobacco smoke (TS) is the source of a number of toxicants affecting the atmosphere and poses a threat to smokers and the whole community. Chemical, physical, and toxicological features of smoking products (vapors as well as mainstream, side stream, and third-hand smoke) have been investigated extensively. Special attention is paid to organic compounds (individually or in combination giving rise to peculiar molecular fingerprints), potentially able to act as “chemical signature” of TS. In this regard, the percent distribution of long-chainnormal, iso, and anteiso alkanes was ascertained as typical of TS. Nevertheless, until now no indexes have been identified as suitable for assessing the global TS contribution to environmental pollution, e.g., the TS percentage in carbonaceous aerosol and in deposited dusts, the only exception consisting in the use of nicotelline as tracer. This paper describes the results of an extensive study aimed at chemically characterizing the nonpolar lipid fraction associated to suspended particulates (PMs) and deposition dusts (DDs) collected at indoor and outdoor locations. Based on the iso, anteiso, and normal C29–C34 alkane profile in the samples as well in tobacco smoke- and no-TS-related emissions (literature data), various parameters describing the distribution of compounds were investigated. Finally, a cumulative variable was identified as the tobacco smoke impact index (TS%) suitable for estimating the TS percentage occurring in the particulate matter. The TS% rates were plotted vs. the exceedance of normal C31 alkane with respect to the average of C29 and C33 homologs, which results higher in TS than in most other emissions, revealing a link in the case of suspended particulates but not of deposited dusts. According to back analysis carried out on all particulate matter sets, it was found that traces of TS affect even remote areas, while inside the smokers’ homes the contributions of TS to PM could account for up to ~61% and ~10%, respectively, in PM and DD. This confirms the need of valuing the health risk posed by TS to humans, by means of tools easy to apply in extensive investigations.Supplementary InformationThe online version contains supplementary material available at 10.1007/s11356-021-16617-0.

A novel approach to Cestrum intermedium (mata-boi): anatomical and physical-chemical characterization, in vitro biological activities, and metabolites of a Brazilian native species

The Brazilian native species Cestrum intermedium, known as mata-boi, induces hepatotoxicity and death when ingested by cattle. While most studies on this species focus on toxicological features, our study is the first to describe the anatomy and in vitro biological activities of Cestrum intermedium. We investigated adult leaves and stems by histochemistry, described their anatomy, performed physical-chemical analysis, determined in vitro antioxidant and antimicrobial activities, and identified secondary metabolites. A few noteworthy anatomical features were the anomocytic stomata on the abaxial surface and the absence of trichomes, in addition to the circular shaped petiole with two projections on the adaxial surface. Histochemical analysis showed chemical markers such as alkaloids, usually reported as toxic, and terpenoids. Potassium nitrate (ATR-FTIR) and lupeol palmitate (NMR) were detected on the crude stem extract. Thermogravimetric and physical-chemical analysis provided fingerprint parameters for the species. Minimal Inhibitory Concentration (MIC) assay revealed that Staphylococcus aureus, Staphylococcus epidermidis, and Candida albicans were weakly inhibited by extract samples. Chloroform and ethyl acetate fractions presented high phenolic content, which resulted in in vitro antioxidant activity. These novel features expand the knowledge about this species, considering that previous studies mainly focused on its toxicity. Our study also provided characteristics that may help in avoiding misidentification between Cestrum members, especially when taxonomic keys cannot be employed, as in the absence of flowers and fruits.

Toxicological Aspects of Iron Oxide Nanoparticles.

Iron oxide nanoparticles (ION), with unique magnetic properties, have attracted huge scientific attention for a wide variety of uses, mostly in the biomedical field, due to their high biocompatibility, ability to cross biological membranes, appropriate surface architecture and easy conjugation with targeting ligands. Their current applications include diagnostic imaging, cell labelling, site-directed drug delivery and anticancer hyperthermia therapy. The ION surface may be modified by coating with different materials, aiming to stabilize the nanoparticles in different environments, to allow biomolecule binding favouring surface attachments with several molecules, and to prolong the recognition time by the immune system. Although the potential benefits of ION are considerable, and more and more ION are being manufactured to meet the demands of the rapidly proliferating field of nanomedicine, there is an urgent need to define their toxicological profile in order to avoid any potential health risks associated with their exposure and to reach optimal benefits of their use. The purpose of this chapter is to de-scribe the current knowledge on the ION toxicological features, addressing their structure and physicochemical characteristics, main exposure pathways and toxicokinetic aspects, interaction with cells, and their toxic effects, with special attention to those at the cellular and molecular level.

A Review of Rhazya stricta Decne Phytochemistry, Bioactivities, Pharmacological Activities, Toxicity, and Folkloric Medicinal Uses.

The local medicinal plant Rhazya stricta Decne is reviewed for its folkloric medicinal, phytochemical, pharmacological, biological, and toxicological features. R. stricta has been used widely in different cultures for various medical disorders. The phytochemical studies performed on the R. stricta extract revealed many alkaloidal and fatty acid compounds. Moreover, several flavonoid and terpenoid compounds were also detected. Pharmacological activates of R. stricta extracts are approved to possess antimicrobial, antioxidant, anticancer, antidiabetic, and antihypertensive activities. Additionally, R. stricta extract was found to hold biological activates such as larvicidal and phytoremediation activates R. stricta extract was found to be toxic, genotoxic, and mutagenic. R. stricta contains novel phytochemical compounds that have not been investigated pharmacologically. Further research is needed through in vitro and in vivo experiments to pave the road for these compounds for medical, veterinary, and ecological uses.

Screening of compounds from Nigerian antidiabetic plants as protein tyrosine phosphatase 1B inhibitor

Several studies have established the antidiabetic properties of several traditional Nigerian plants, but only limited studies have elucidated their mechanism of action. Protein tyrosine phosphatase 1B (PTP1B), a negative regulator of the insulin signalling pathway, is a drug target for the management of diabetes. However, to date, there is no available commercial drug with specificity for targeting PTP1B. This study sought to investigate compounds identified in Nigerian medicinal plants with therapeutic potential as inhibitors of PTP1B. A chemical library comprising more than a thousand compounds identified from Nigerian medicinal plants was docked with PTP1B; The prepared compounds were filtered using Lipinski's rule of five (RO5) and consequently used for molecular docking analysis. The binding free energy of the best ten (10) drug-like compounds was computed, then their pharmacokinetic and toxicological features were determined and compared with three standard PTP1B inhibitors. A 2D-QSAR model was constructed from an experimental dataset retrieved from literature before confirming its robustness through external validation. Finally, the reactivity and stability of the compounds, coupled with atomic regions rich in electron acceptor and donor capacity, were investigated using Jaguar fast engine. The ten top-scoring compounds had a more favourable binding affinity with PTP1B than the standard inhibitors, and they interacted with crucial residues that enhance inhibition of the protein. Generally, the natural compounds had remarkable pharmacokinetic properties and minor unwanted toxicities compared with the reference inhibitors. The external validated QSAR model (KPLS_Molprint2D_9) demonstrated that the compounds had good bioactivity against PTP1B. Through DFT calculation, blighinone was found to be the most chemically reactive compound, and electron deficit and rich regions of the compounds accepted and donated hydrogen to PTP1B amino acid residues during intermolecular interaction. The knowledge obtained in this study may help reveal natural compounds that can become potent inhibitors of PTP1B.