Preparation of bio-synthesized Ag nanoparticles and assessment of their antidiabetic and antioxidant potential against STZ-induced diabetic albino rats.

Bio-synthesized silver nanoparticles (AgNPs) were successfully obtained using the leaf extract from Ventilago maderaspatana. Extensive analysis was conducted to evaluate the physical and chemical characteristics of the bioderived AgNPs. XRD analysis confirmed their cubic structure, and revealed a well-defined size distribution with average crystallite size of 11.7 nm. FE-SEM and TEM images visually supported the observed size range. The presence of plant-mediated phytochemicals on the surface of AgNPs was confirmed through DLS, FTIR, and TGA/DTA studies. To assess their antidiabetic potential, rats were induced with streptozotocin, resulting in elevated levels of biochemical parameters associated with diabetes. Conversely, serum insulin levels (2.50 ± 0.55) and glucokinase activity (64.50 ± 8.66) decreased. However, treatment with AgNPs demonstrated a dose-dependent reduction in blood glucose, total protein, albumin, and HbA1c levels, effectively restoring them to normal ranges. Moreover, the treatment significantly increased insulin levels (7.55 ± 0.63) and glucokinase activity (121.50 ± 4.60), indicating the antidiabetic potential of V. maderaspatana-mediated AgNPs. Notably, the exitance of phytochemicals, like flavonoids and phenols, on the surface of AgNPs facilitated their ability to neutralize reactive oxygen species (ROS) through electron donation. This property enhanced their overall antidiabetic efficiency.

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.

Inhibition of oxidative stress and advanced glycation end-product formation in purified BSA/glucose glycation system by polyphenol extracts of selected nuts from Pakistan.

Glycation generates advanced glycation end products (AGE) and its intermediates, thus increasing the risk of developing various ailments including diabetes mellitus. Current study was planned to explore the antioxidant and antiglycation potential of selected nuts viz, Juglans regia (Walnut), Prunus dulcis (Almond), Pistacia vera (Pistachio), and Arachis hypogaea (Peanut), locally available and readily consumed in Faisalabad, Pakistan, for their health-promoting properties. The prepared methanolic extracts of selected nuts were tested for biological activities including the antioxidant and antiglycation potential. The effect of these extracts against oxidation and AGE formation was evaluated by in vitro method using bovine serum albumin (BSA)-glucose system. Juglans regia, Pistacia vera, and Arachis hypogaea were found rich in phenolics and flavonoids contents with increased reducing potential and least IC50 due to the DPPH free radical scavenging inhibition. Dose- and time-dependent inhibition of glucose-induced advanced glycation end-product (AGE) was exhibited by fruit extracts through in vitro bovine serum albumin (BSA)-glucose system. Juglans regia and Pistacia vera were predominantly effective in the inhibition of early and intermediary glycation products at different incubation conditions. The study indicated that the extracts of selected nuts possess significant antioxidant capacity and are rich in phenolics and flavonoids, making them useful supplements as an important part of a balanced diet.

Phytobioactive compounds as therapeutic agents for human diseases: A review.

Phytobioactive compounds are plant secondary metabolites and bioactive compounds abundantly present in medicinal plants and have remarkable therapeutic potential. Oxidative stress and antibiotic resistance are major causes of present-day ailments such as diabetes, atherosclerosis, cardiovascular disorders, cancer, and inflammation. The data for this review were collected from Google Scholar, PubMed, Directory of Open Access Journals (DOAJ), and Science Direct by using keywords: "Medicinal plants, Phytobioactive compounds, Polyphenols, Alkaloids, Carotenoids etc." Several studies have reported the pharmacological and therapeutic potential of the phytobioactives. Polyphenols, alkaloids, terpenes, and polysaccharides isolated from medicinal plants showed remarkable antioxidant, anticancer, cytotoxic, anti-inflammatory, cardioprotective, hepatoprotective, immunomodulatory, neuroprotective, and antidiabetic activities. This literature review was planned to provide comprehensive insight into the biopharmacological and therapeutic potential of phytobioactive compounds. The techniques used for the extraction and isolation of phytobioactive compounds, and bioassays required for their biological activities such as antioxidant, antimicrobial, anti-inflammatory, and cytotoxic activities, have been discussed. Characterization techniques for the structural elucidation of phytobioactive compounds such as HPLC, TLC, FTIR, GC-MS/MS, and NMR have also been discussed. This review concludes that phytobioactive compounds may be used as potential alternative to synthetic compounds as therapeutic agents for the treatment of various diseases.

Greater efficiency of polyherbal drug encapsulated biosynthesized chitosan nano-biopolymer on diabetes and its complications.

Diabetes is a highly complex disease that has an adverse impact on the lives of individuals, and the current medicines used to manage diabetes have obvious side effects. Medicinal plants, on the other hand, may serve as an alternate source of anti-diabetic drugs. A polyherbal combination has a higher and more extensive therapeutic potential than a single herb. Yet, due to deterioration during the absorption process, the usage of this drug still yields inadequate results. Encapsulation of polyherbal drug with chitosan nanoparticles is one of the key ways to solve this problem due to its biocombatibilty, slow and targeted drug delivery characteristics. In the present study, the chitosan was derived from prawn shell and the chitosan nanoparticles had been prepared by ionic-gelation method. The anti-diabetic polyherbal drug (Andrographis paniculata, Andrographis alata, Adhatoda zeylanica, Gymnema sylvestre, Syzygium cumini, and Justicia glabra) was encapsulated with a bio-derived chitosan biopolymer. The drug loading efficiency was about 85 %. The chemical and physical properties of the chitosan and drug-loaded chitosan nanoparticles had been analyzed by FT-IR absorption, XRD, SEM, TEM and EDAX analysis. The antidiabetic efficiency, hepatoprotective activity and antihyperlipedimic activity of the chitosan nanoparticles, polyherbal drug and polyherbal drug encapsulated with chitosan nanoparticles were assessed in a group of rats. The polyherbal drug reduced the serum glucose level from 306.4 mg/dL to 134.47 mg/dL, while the polyherbal drug encapsulated with chitosan nanoparticles reduced to 127.017 mg/dL. This was very close to the serum glucose level of non-diabetic rat (124.65 mg/dL). Further, it considerably increased the insulin level close to that of non-diabetic rat. Thus, the polyherbal drug encapsulated with chitosan nanoparticles showed superior efficiency in antidiabetic and also diabetic complications.

Mineral Profile, Antioxidant, Anti-Inflammatory, Antibacterial, Anti-Urease and Anti-α-Amylase Activities of the Unripe Fruit Extracts of Pistacia atlantica.

Pistacia Atlantica in folk medicine is used by Algerian traditional healers for treating a wide variety of diseases and conditions including dyspepsia, digestive problems, peptic ulcers, and, in particular, inflammatory diseases. The present study aimed to assess the phytochemical composition, in vitro antioxidant activity (using 2,2-diphenyl-1-picrylhydrazyl (DPPH), ABTS+, and reducing power methods), enzyme inhibitory activity (towards α-amylase and urease), antibacterial activity, and in vivo anti-inflammatory activity of the unripe fruit extracts of Pistacia atlantica collected from different parts of the Djelfa region of Algeria. According to the findings, various aqueous extracts exhibited significant antioxidant and enzymatic activities in all tests, but showed that they have a weak inhibitory effect against all tested bacterial strains. Twenty-one minerals comprising both macro- and microelements (Ba, Br, Ca, Cl, Co, Cr, Cs, Eu, Fe, K, Mg, Mn, Mo, Na, Rb, Sb, Sc, Sr, Th, U, and Zn) were determined using the technique of neutron activation analysis (INAA). The result indicates that the concentration of the mineral element is close to the minimal FAO recommendation. In addition, the result revealed significant anti-inflammatory activities. The data generated can be a valuable source of information for the pharmaceutical industry and medical research. These results suggest that the unripe fruit extracts of Pistacia atlantica have an appropriate potential to be utilized across a wide range of contexts as an agent with multifunctional uses, as well as a natural remedy for other physiological diseases.

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.

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.

Perspective Insights to Bio-Nanomaterials for the Treatment of Neurological Disorders.

The significance of biomaterials is well appreciated in nanotechnology, and its use has resulted in major advances in biomedical sciences. Although, currently, very little data is available on the clinical trial studies for treatment of neurological conditions, numerous promising advancements have been reported in drug delivery and regenerative therapies which can be applied in clinical practice. Among the commonly reported biomaterials in literature, the self-assembling peptides and hydrogels have been recognized as the most potential candidate for treatment of common neurological conditions such as Alzheimer's, Parkinson's, spinal cord injury, stroke and tumors. The hydrogels, specifically, offer advantages like flexibility and porosity, and mimics the properties of the extracellular matrix of the central nervous system. These factors make them an ideal scaffold for drug delivery through the blood-brain barrier and tissue regeneration (using stem cells). Thus, the use of biomaterials as suitable matrix for therapeutic purposes has emerged as a promising area of neurosciences. In this review, we describe the application of biomaterials, and the current advances, in treatment of statistically common neurological disorders.

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.

Minerals, Essential Oils, and Biological Properties of Melissa officinalis L.

This study describes the minerals elements, chemical composition, antioxidant and antimicrobial activities of Algerian Melissa officinalis plant. The essential oil (EO) was extracted by hydrodistillation (HD) using a Clevenger-type apparatus of dry leaves of M. officinalis and was analyzed by two techniques, gas chromatography coupled with flame ionization (GC-FID) and gas chromatography coupled with mass spectrometry (GC-MS). Eighteen minerals comprising both macro- and microelements (As, Br, K, La, Na, Sb, Sm, Ba, Ca, Ce, Co, Cr, Cs, Fe, Rb, Sc, Th, and Zn) were determined using neutron activation analysis technique for the first time from Algerian Melissa officinalis plant. Seventy-eight compounds were identified in the essential oil, representing 94.090% of the total oil and the yields were 0.470%. The major component was geranial (45.060%). Other predominant components were neral (31.720%) and citronellal (6.420%). The essential oil presented high antimicrobial activity against microorganisms, mainly five human pathogenic bacteria, one yeast, Candida albicans, and two phytopathogenic fungi. The results can be used as a source of information for the pharmaceutical industry and medical research.

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.

Effect of Extraction Methods on Polyphenols, Flavonoids, Mineral Elements, and Biological Activities of Essential Oil and Extracts of Mentha pulegium L.

Our study evaluated the in vitro antioxidant properties, antibacterial and antifungal activities, anti-inflammatory properties, and chemical composition of the essential oils (EOs), total phenol, and total flavonoid of wild Mentha pulegium L. This study also determined the mineral (nutritional and toxic) elements in the plant. The EOs were extracted using three techniques-hydro distillation (HD), steam distillation (SD), and microwave-assisted distillation (MAD)-and were analyzed using chromatography coupled with flame ionization (GC-FID) and gas chromatography attached with mass spectrometry detector (GC-MS). The antioxidant effects of the EOs were tested with 2,2-diphenyl-1-picrylhydrazyl (DPPH) and ABTS (2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid), while the antibacterial and antifungal activities of the EO and methanolic extract were tested using Staphylococcus aureus, Bacillus subtilis, Pseudomonas aeruginosa, Escherichia coli, and Candida albicans. Twenty-six compounds were identified in the essential oil, representing 97.73% of the total oil, with 0.202% yield. The major components were pulegone (74.81%), menthone (13.01%) and piperitone (3.82%). Twenty-one elements, including macro- and micro-elements (Ba, Br, Ca, Cl, Co, Cr, Cs, Eu, Fe, K, Mg, Mn, Mo, Na, Rb, Sb, Sc, Sr, Th, U and Zn), were detected using neutron activation analysis (INAA) and inductively coupled plasma optical emission spectrometry (ICP-OES), with the concentration of mineral element close to the FAO recommendation. The results show that the EOs and extracts from Mentha pulegium L. had significant antimicrobial activities against the microorganisms, including five human pathogenic bacteria, one yeast (Candida albicans), and one phytopathogenic fungi. The in vivo anti-inflammatory activities of the leaf extracts were confirmed. The results indicate that the EOs and extracts from Mentha pulegium L. have promising applications in the pharmaceutical industries, clinical applications, and in medical research.

Evaluation of Annona muricata Acetogenins as Potential Anti-SARS-CoV-2 Agents Through Computational Approaches.

Annona muricata, a tropical plant which has been extensively used in ethnomedicine to treat a wide range of diseases, from malaria to cancer. Interestingly, this plant has been reported to demonstrate significant antiviral properties against the human immunodeficiency virus, herpes simplex virus, human papilloma virus, hepatitis C virus and dengue virus. Additionally, the bioactive compounds responsible for antiviral efficacy have also shown to be selectively cytotoxic while inhibiting tumorigenic cell growth without affecting the normal cell growth. Annonaceous Acetogenins are a class of bioactive compounds exclusive to the Annonaceae family at which the plant A. muricata belongs. In the current study, we have created a library of Acetogenins unique to the plant, comprising of Annomuricin A, Annomuricin B, Annomuricin C, Muricatocin C, Muricatacin, cis-Annonacin, Annonacin-10-one, cis-Goniothalamicin, Arianacin and Javoricin, for in silico and theoretical evaluations against the SARS-CoV-2 spike protein in an attempt toward promotion of plant based drug development for the current pandemic of coronavirus disease 2019 (COVID-19). We found that all the Acetogenins showing in silico spike protein significantly docking with good binding affinities. Moreover, we envision A. muricata Acetogenins can be further studied by in vitro and in vivo models to identify potential anti-SARS-CoV-2 agents.