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This study investigates the antibacterial and antifungal properties of eight benzene sulfonamide derivatives synthesized and reported in our previous study using a combination of experimental and computational methods. In antimicrobial activity, the MIC values of all the eight tested compounds were approximately 125.00 μg/mL against eight bacterial and three fungal strains. However, the compound 8 was found to exhibit remarkable activity (MIC=31.25 μg/mL) against E. faecalis (bacteria) and C. parapsilosis (fungi) compared to the MIC values of rest of the compounds. Results of in-silico drug-likeness and pharmacokinetic (ADMET) assessment reveal that all the title compounds met the compliance of criteria of drug-likeness rules and exhibited zero violations across. Results of docking study demonstrates that the compound 8 showed the highest binding affinity (-8.7 kcal/mol) among the compounds against S. aureus TyrRS, whereas against S. aureus DHFR, compound 2 exhibited the highest binding afinity of -8.5 kcal/mol. Among the compounds docked against C. albicans DHFR and C. albicans N-myristoyl transferase, compound 8 demonstrated the highest binding affinity of -8 kcal/mol and -8.9 kcal/mol, respectively. The results of antibacterial and antifungal experiments substantiate the predictions made by computational studies and provide empirical evidence of antibacterial and antifungal potential of the reported benzene sulfonamide derivatives.

Abstract Cyclooxygenase (COX) and Lipoxygenase (LOX) are essential enzymes for arachidonic acid (AA) to eicosanoids conversion. These AA-derived eicosanoids are essential for initiating immunological responses, causing inflammation, and resolving inflammation. Dual COX/5-LOX inhibitors are believed to be promising novel anti-inflammatory agents. They inhibit the synthesis of prostaglandins (PGs) and leukotrienes (LTs), but have no effect on lipoxin formation. This mechanism of combined inhibition circumvents certain limitations for selective COX-2 inhibitors and spares the gastrointestinal mucosa. Natural products, i.e. spice chemicals and herbs, offer an excellent opportunity for drug discovery. They have proven anti-inflammatory properties. However, the potential of a molecule to be a lead/ drug candidate can be much more enhanced if it has the property of inhibition in a dual mechanism. Synergistic activity is always a better option than the molecule's normal biological activity. Herein, we have explored the dual COX/5-LOX inhibition property of the three major potent phytoconsituents (curcumin, capsaicin, and gingerol) from Indian spices using in silico tools and biophysical techniques in a quest to identify their probable inhibitory role as anti-inflammatory agents. Results revealed the dual COX/5-LOX inhibitory potential of curcumin. Gingerol and capsaicin also revealed favorable results as dual COX/5-LOX inhibitors. Our results are substantiated by target similarity studies, molecular docking, molecular dynamics, energy calculations, DFT, and QSAR studies. In experimental inhibitory (in vitro) studies, curcumin exhibited the best dual inhibitory activities against COX-1/2 and 5-LOX enzymes. Capsaicin and gingerol also showed inhibitory potential against both COX and LOX enzymes. In view of the anti-inflammatory potential these spice chemicals, this research could pave the way for more scientific exploration in this area for drug discovery.

Breast cancer is one of the most common malignancies in women, afflicting millions of lives each year. Our current study suggests that the development of the most promising 7-substituted -1-(4-(piperidine-1-yl methoxy)benzyl)-1H-indole-3-carboxamide derivatives results in potent anticancer agents through in-silico investigations. The molecular docking was performed against estrogen receptor alpha (ER-α) positive (PDB ID: 3UUD) of breast cancer cells to anticipate the binding modes of the designed compounds and the likely mode of action. The interactions between the ligands and amino acid residues were thoroughly elucidated. The stability of the docked protein-ligand complexes was further confirmed by 100 ns molecular simulations methods. From in-silico studies, indole-based benzamides exhibited satisfactory physicochemical, drug-likeness and toxicity properties. To conclude, the most promising substituted benzamide analogs on the indole ring could serve as a possible modulator against ER-α positive breast cancer.

Polyphenols, as secondary metabolites ubiquitous in plant sources, have emerged as pivotal bioactive compounds with far-reaching implications for human health. Plant polyphenols exhibit direct or indirect associations with biomolecules capable of modulating diverse physiological pathways. Due to their inherent abundance and structural diversity, polyphenols have garnered substantial attention from both the scientific and clinical communities. The review begins by providing an in-depth analysis of the chemical intricacies of polyphenols, shedding light on their structural diversity and the implications of such diversity on their biological activities. Subsequently, an exploration of the dietary origins of polyphenols elucidates the natural plant-based sources that contribute to their global availability. The discussion extends to the bioavailability and metabolism of polyphenols within the human body, unraveling the complex journey from ingestion to systemic effects. A central focus of the review is dedicated to unravelling the antioxidant effects of polyphenols, highlighting their role in combating oxidative stress and associated health conditions. The comprehensive analysis encompasses their impact on diverse health concerns such as hypertension, allergies, aging, and chronic diseases like heart stroke and diabetes. Insights into the global beneficial effects of polyphenols further underscore their potential as preventive and therapeutic agents. This review article critically examines the multifaceted aspects of dietary polyphenols, encompassing their chemistry, dietary origins, bioavailability/metabolism dynamics, and profound antioxidant effects. The synthesis of information presented herein aims to provide a valuable resource for researchers, clinicians, and health enthusiasts, fostering a deeper understanding of the intricate relationship between polyphenols and human health.

Abstract The Kirsten rat sarcoma (KRAS) oncoprotein has been on drug hunters list for decades now. Initially considered undruggable, recent advances have successfully broken the jinx through covalent inhibition that exploits the mutated cys12 in the switch II binding pocket (KRASG12C). Though this approach has achieved some level of success, patients with mutations other than cys12 are still uncatered for. KRASG12D is the most frequent KRAS mutated oncoprotein. It is only until recently, MRTX1133 has been discovered as a potential inhibitor of KRASG12D. This study seeks to unravel the structural binding mechanism of MRTX1133 as well as identify potential drug leads of KRASG12D based on structural binding characteristics of MRTX1133. It was revealed that MRTX1133 binding stabilizes the binding site by increasing the hydrophobicity which resultantly induced positive correlated movements of switches I and II which could disrupt their interaction with effector and regulatory proteins. Furthermore, MRTX1133 interacted with critical residues; Asp69 (− 4.54 kcal/mol), His95 (− 3.65 kcal/mol), Met72 (− 2.27 kcal/mol), Thr58 (− 2.23 kcal/mol), Gln99 (− 2.03 kcal/mol), Arg68 (− 1.67 kcal/mol), Tyr96 (− 1.59 kcal/mol), Tyr64 (− 1.34 kcal/mol), Gly60 (− 1.25 kcal/mol), Asp12 (− 1.04 kcal/mol), and Val9 (− 1.03 kcal/mol) that contributed significantly to the total free binding energy of − 73.23 kcal/mol. Pharmacophore-based virtual screening based on the structural binding mechanisms of MRTX1133 identified ZINC78453217, ZINC70875226 and ZINC64890902 as potential KRASG12D inhibitors. Further, structural optimisations and biochemical testing of these compounds would assist in the discovery of effective KRASG12D inhibitors.

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative organism of coronavirus disease 2019 (COVID-19) which poses a significant threat to public health worldwide. Though there are certain recommended drugs that can cure COVID-19, their therapeutic efficacy is limited. Therefore, the early and rapid detection without compromising the test accuracy is necessary in order to provide an appropriate treatment for the disease suppression. Main body Nanoparticles (NPs) can closely mimic the virus and interact strongly with its proteins due to their morphological similarities. NPs have been widely applied in a variety of medical applications, including biosensing, drug delivery, antimicrobial treatment, and imaging. Recently, NPs-based biosensors have attracted great interest for their biological activities and specific sensing properties, which allows the detection of analytes such as nucleic acids (DNA or RNA), aptamers, and proteins in clinical samples. Further, the advances of nanotechnologies have enabled the development of miniaturized detection systems for point-of-care biosensors, a new strategy for detecting human viral diseases. Among the various NPs, the specific physicochemical properties of gold NPs (AuNPs) are being widely used in the field of clinical diagnostics. As a result, several AuNP-based colorimetric detection methods have been developed. Short conclusion The purpose of this review is to provide an overview of the development of AuNPs-based biosensors by virtue of its powerful characteristics as a signal amplifier or enhancer that target pathogenic RNA viruses that provide a reliable and effective strategy for detecting of the existing or newly emerging SARS-CoV-2.

To valorise the bioactive constituents abundant in leaves and other parts of medicinal plants with the objective to minimize the plant-based wastes, this study was undertaken. The main bioactive constituent of Andrographis paniculata, an Asian medicinal plant, is andrographolide (AG, a diterpenoid), which has shown promising results in the treatment of neurodegenerative illnesses. Continuous electrical activity in the brain is a hallmark of the abnormal neurological conditions such as epilepsy (EY). This can lead to neurological sequelae. In this study, we used GSE28674 as a microarray expression profiling dataset to identify DEGs associated with andrographolide and those with fold changes >1 and p-value

Adhatoda vasica (also called Vasaka) is a traditional medicinal herb used traditionally for the relief of cough, asthma, nasal congestion, bronchial inflammation, upper respiratory infections, bleeding disorders, skin diseases, leprosy, tuberculosis, diabetes, allergic conditions, rheumatism, tumor, and many more diseases. The present study aims to investigate the biological activities of vasicine, a potent alkaloid from A. vasica with different biological/ pharmacological assays and in silico techniques. Vasicine showed antimicrobial activity as evidenced fromthe colony-forming unit assay. It showed antioxidant activity in ABTS scavenging assay (IC50 = 11.5 μg/ml), ferric reducing power assay (IC50 = 15 μg/ml), DPPH radical scavenging assay (IC50 = 18.2 μg/ml), hydroxyl radical scavenging assay (IC50 = 22 μg/ml), and hydrogen peroxide assay (IC50 = 27.8 μg/ml). It also showed anti-inflammatory activity in proteinase inhibitory assay (IC50 = 76 μg/ml), BSA method (IC50 = 51.7 μg/ml), egg albumin method (IC50 = 53.2 μg/ml), and lipooxygenase inhibition assay (IC50 = 76 μg/ml). Vasicine showed antidiabetic activity in α-amylase inhibition assay (IC50 = 47.6 μg/ml), α-glucosidase inhibition assay (IC50 = 49.68 μg/ml), and non-enzymatic glycosylation of hemoglobin assay. It showed antiviral activity against HIV-protease (IC50 = 38.5 μg/ml). Vasicine also showed anticancer activity against lung cancer cells (IC50 = 46.5 μg/ml) and human fibroblast cells (IC50 = 82.5 μg/ml). In silico studies revealed that similar to the native ligands, vasicine also showed a low binding energy, i.e., good binding affinity for the active binding sites and interacted with α-amylase (-6.7 kcal/mol), α-glucosidase (-7.6 kcal/mol), cyclooxygenase (-7.4 kcal/mol), epidermal growth factor receptor (-6.4 kcal/mol), lipooxygenase (-6.9 kcal/mol), and HIV-protease (-6.4 kcal/mol). The present study ascertains the potential of vasicine as a bioactive compound isolated from A. vasica having therapeutic usefulness in many human diseases.

Abstract Background From the start of the twenty-first century up to the year 2021, RNA viruses are the main causative agents of the majority of the disease outbreaks the world has confronted. Recently published reviews on SARS-CoV-2 have mainly focused on its structure, development of the outbreak, relevant precautions, management trials and available therapies. However, in this review, we aim to explore the history, evolution of all coronaviruses and the associated viral outbreaks along with the diagnostics for COVID-19 in the twenty-first century. Main body We have focused on different RNA viruses’ viz. SARS-CoV, MERS-CoV, and SARS-CoV-2, their classification, and the various disease outbreaks caused by them. In the subsequent section, the comparison of different RNA viruses affecting humans has been made based on the viral genome, structure, time of the outbreak, mode of spread, virulence, causative agents, and transmission. Due to the current mayhem caused by the rapidly emerging virus, special attention is given to SARS-CoV-2, its genome updates, and infectivity. Finally, the current diagnostic techniques such as nucleic acid testing (real time-polymerase chain reaction and loop-mediated isothermal amplification), CRISPR-based diagnostics (CRISPR based DETECTR assay, CRISPR based SHERLOCK test, AIOD-CRISPR, FELUDA, CREST), chest radiographs (computed tomography, X-ray), and serological tests (Lateral flow assay, enzyme-linked immunosorbent assay, chemiluminescent immunoassay, neutralization assay, nano-sensors, blood test, viral sequencing) with their pros and cons, and future diagnostic prospective have been described. Conclusions The present gloomy scenario mandates clinical manifestations, contact tracing, and laboratory tests as important parameters that need to be taken into consideration to make the final diagnosis.

Nanobiotechnology is a burgeoning field of research with applications in cancer treatment, targeted chemotherapy, and molecular diagnosis. This study aims at the fabrication of silver nanoparticles using embelin derived from Embelia ribes to evaluate its anticancer property. Silver nanoparticles (AgNPs) have emerged as a novel nano-carrier for therapeutic agents with a wide range of medical capabilities due to their unique structural, physicochemical, and optical features. In our study, the particle size of fabricated AgNPs was measured as 25 nm, and the zeta potential was recorded as −5.42 mV, which indicates the good stability of embelin-derived AgNPs. The crystalline surface morphology was observed by SEM analysis. The FT-IR spectrum confirmed the reduction in silver ions (Ag+) by embelin, and the TEM analysis exhibited polydispersed Ag+ of 20–30 nm. The anticancer potential of embelin-fabricated AgNPs was investigated using in vitro studies on lung cancer cells by the MTT assay. The results revealed significant dose-dependent inhibition of cell proliferation against A549 cell lines. Embelin AgNP-induced apoptosis was measured by the annexin-V PI apoptosis assay, which exhibited significantly low necrotic cells as compared to apoptotic cells. Finally, the findings of our study suggest the anticancer potential of biofabricated embelin AgNPs, particularly against lung cancer cells.

The open innovation hub Digital Health and Patient Safety Platform (DHPSP) was recently established with the purpose to invigorate collaborative scientific research and the development of new digital products and personalized solutions aiming to improve human health and patient safety. In this study, we evaluated the effectiveness of a Twitter-based campaign centered on using the hashtag #DHPSP to promote the visibility of the DHPSP initiative. Thus, tweets containing #DHPSP were monitored for five weeks for the period 20.10.2020–24.11.2020 and were analyzed with Symplur Signals (social media analytics tool). In the study period, a total of 11,005 tweets containing #DHPSP were posted by 3020 Twitter users, generating 151,984,378 impressions. Analysis of the healthcare stakeholder-identity of the Twitter users who used #DHPSP revealed that the most of participating user accounts belonged to individuals or doctors, with the top three user locations being the United States (501 users), the United Kingdom (155 users), and India (121 users). Analysis of co-occurring hashtags and the full text of the posted tweets further revealed that the major themes of attention in the #DHPSP Twitter-community were related to the coronavirus disease 2019 (COVID-19), medicine and health, digital health technologies, and science communication in general. Overall, these results indicate that the #DHPSP initiative achieved high visibility and engaged a large body of Twitter users interested in the DHPSP focus area. Moreover, the conducted campaign resulted in an increase of DHPSP member enrollments and website visitors, and new scientific collaborations were formed. Thus, Twitter campaigns centered on a dedicated hashtag prove to be a highly efficient tool for visibility-promotion, which could be successfully utilized by healthcare-related open innovation platforms or initiatives.

Severe acute respiratory syndrome coronavirus disease (SARS-CoV-2) induced coronavirus disease 2019 (COVID-19) pandemic is the present worldwide health emergency. The global scientific community faces a significant challenge in developing targeted therapies to combat the SARS-CoV-2 infection. Computational approaches have been critical for identifying potential SARS-CoV-2 inhibitors in the face of limited resources and in this time of crisis. Main protease (Mpro) is an intriguing drug target because it processes the polyproteins required for SARS-CoV-2 replication. The application of Ayurvedic knowledge from traditional Indian systems of medicine may be a promising strategy to develop potential inhibitor for different target proteins of SARS-CoV-2. With this endeavor, we docked bioactive molecules from Triphala, an Ayurvedic formulation, against Mpro followed by molecular dynamics (MD) simulation (100 ns) to investigate their inhibitory potential against SARS-CoV-2. The top four best docked molecules (terflavin A, chebulagic acid, chebulinic acid, and corilagin) were selected for MD simulation study and the results obtained were compared to native ligand X77. From docking and MD simulation studies, the selected molecules showed promising binding affinity with the formation of stable complexes at the active binding pocket of Mpro and exhibited negative binding energy during MM-PBSA calculations, indication their strong binding affinity with the target protein. The identified bioactive molecules were further analyzed for drug-likeness by Lipinski’s filter, ADMET and toxicity studies. Computational (in silico) investigations identified terflavin A, chebulagic acid, chebulinic acid, and corilagin from Triphala formulation as promising inhibitors of SARS-CoV-2 Mpro, suggesting experimental (in vitro/in vivo) studies to further explore their inhibitory mechanisms.

Dietary polyphenols including phenolic acids, flavonoids, catechins, tannins, lignans, stilbenes, and anthocyanidins are widely found in grains, cereals, pulses, vegetables, spices, fruits, chocolates, and beverages like fruit juices, tea, coffee and wine. In recent years, dietary polyphenols have gained significant interest among researchers due to their potential chemopreventive/protective functions in the maintenance of human health and diseases. It is believed that dietary polyphenols/flavonoids exert powerful antioxidant action for protection against reactive oxygen species (ROS)/cellular oxidative stress (OS) towards the prevention of OS-related pathological conditions or diseases. Pre-clinical and clinical evidence strongly suggest that long term consumption of diets rich in polyphenols offer protection against the development of various chronic diseases such as neurodegenerative diseases, cardiovascular diseases (CVDs), cancer, diabetes, inflammatory disorders and infectious illness. Increased intake of foods containing polyphenols (for example, quercetin, epigallocatechin-3-gallate, resveratrol, cyanidin etc.) has been claimed to reduce the extent of a majority of chronic oxidative cellular damage, DNA damage, tissue inflammations, viral/bacterial infections, and neurodegenerative diseases. It has been suggested that the antioxidant activity of dietary polyphenols plays a pivotal role in the prevention of OS-induced human diseases. In this narrative review, the biological/pharmacological significance of dietary polyphenols in the prevention of and/or protection against OS-induced major human diseases such as cancers, neurodegenerative diseases, CVDs, diabetes mellitus, cancer, inflammatory disorders and infectious diseases have been delineated. This review specifically focuses a current understanding on the dietary sources of polyphenols and their protective effects including mechanisms of action against various major human diseases.

Endometrial cancer (EC) is the sixth most prevalent type of cancer among women. Kinases, enzymes mediating the transfer of adenosine triphosphate (ATP) in several signaling pathways, play a significant role in carcinogenesis and cancer cells’ survival and proliferation. Cyclin-dependent kinases (CDKs) are involved in EC pathogenesis; therefore, CDK inhibitors (CDKin) have a noteworthy therapeutic potential in this type of cancer, particularly in EC type 1. Natural compounds have been used for decades in the treatment of cancer serving as a source of anticancer bioactive molecules. Many phenolic and non-phenolic natural compounds covering flavonoids, stilbenoids, coumarins, biphenyl compounds, alkaloids, glycosides, terpenes, and terpenoids have shown moderate to high effectiveness against CDKin-mediated carcinogenic signaling pathways (PI3K, ERK1/2, Akt, ATM, mTOR, TP53). Pharmaceutical regimens based on two natural compounds, trabectedin and ixabepilone, have been investigated in humans showing short and midterm efficacy as second-line treatments in phase II clinical trials. The purpose of this review is twofold: the authors first provide an overview of the involvement of kinases and kinase inhibitors in the pathogenesis and treatment of EC and then discuss the existing evidence about natural products’ derived kinase inhibitors in the management of the disease and outline relevant future research.

Advancement in nanotechnology has unleashed the therapeutic potentials of dietary polyphenols by enhancing bioavailability, improving biological half-life, and allowing site-specific drug delivery. In this review, through citation of relevant literature reports, we discuss the application of nano-pharmaceutical formulations, such as solid lipid nanoparticles, nano-emulsions, nano-crystals, nano-polymersomes, liposomes, ethosomes, phytosomes, and invasomes for dietary polyphenols. Following this, we highlight important studies concerning different combinations of nano formulations with dietary polyphenols (also known as nanophytopolyphenols). We also provide nano-formulation paradigms for enhancing the physicochemical properties of dietary polyphenols. Finally, we highlight the latest patents that were granted on nano-formulations of dietary polyphenols. Based on our review, we observe that nanosized delivery of herbal constituents, spices, and dietary supplements have the ability to improve biological processes and address issues connected with herbal treatments.

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.

Migraine, as the seventh most disabling neurological disease with 26.9% prevalence in Saudi females, lacks studies on identifying associated genes and pathways with migraines in the Arab population. This case control study aims to identify the migraine-associated novel genes and risk variants. More than 1900 Arab ancestry young female college students were screened: 103 fulfilled the ICHD-3 criteria for migraine and 20 cases confirmed in the neurology clinic were included for the study with age-matched healthy controls. DNA from blood samples were subjected to paired-end whole-exome sequencing. After quality control, 3365343 missense, frameshift, missense splice region variants and insertion–deletion (indels) polymorphisms were tested for association with migraine. Significant variants were validated using Sanger sequencing. A total of 17 (p-value 9.091 × 10−05) functional variants in 12 genes (RETNLB, SCAI, ADH4, ESPL1, CPT2, FLG, PPP4R1, SERPINB5, ZNF66, ETAA1, EXO1 and CPA6) were associated with higher migraine risk, including a stop-gained frameshift (-13-14*SX) variant in the gene RETNLB (rs5851607; p-value 3.446 × 10−06). Gene analysis revealed that half of the significant novel migraine risk genes were expressed in the temporal lobe (p-value 0.0058) of the cerebral cortex. This is the first study exploring the migraine risk of 17 functional variants in 12 genes among Saudi female migraineurs of Arab ancestry using whole-exome sequencing. Half of the significant genes were expressed in the temporal lobe, which expands migraine pathophysiology and early identification using biomarkers for research possibilities on personalised genetics.

Cigarette smoking has been responsible for causing many life-threatening diseases such as pulmonary and cardiovascular diseases as well as lung cancer. One of the prominent health implications of cigarette smoking is the oxidative damage of cellular constituents, including proteins, lipids, and DNA. The oxidative damage is caused by reactive oxygen species (ROS, oxidants) present in the aqueous extract of cigarette smoke (CS). In recent years, there has been considerable interest in the potential health benefits of dietary polyphenols as natural antioxidant molecules. Epidemiological studies strongly suggest that long-term consumption of diets (fruits, vegetables, tea, and coffee) rich in polyphenols offer protective effects against the development of cancer, cardiovascular diseases, diabetes, osteoporosis, and neurodegenerative diseases. For instance, green tea has chemopreventive effects against CI-induced lung cancer. Tea might prevent CS-induced oxidative damages in diseases because tea polyphenols, such as catechin, EGCG, etc., have strong antioxidant properties. Moreover, apple polyphenols, including catechin and quercetin, provide protection against CS-induced acute lung injury such as chronic obstructive pulmonary disease (COPD). In CS-induced health problems, the antioxidant action is often accompanied by the anti-inflammatory effect of polyphenols. In this narrative review, the CS-induced oxidative damages and the associated health implications/pathological conditions (or diseases) and the role of diets rich in polyphenols and/or dietary polyphenolic compounds against various serious/chronic conditions of human health have been delineated.

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.

Environmental exposure to arsenic has been profoundly associated with chronic systemic disorders, such as neurodegeneration, in both experimental models and clinical studies. The neuronal cells of the brain and the nervous system have a limited regeneration capacity, thus making them more vulnerable to exposure to xenobiotics, leading to long-lasting disabilities. The functional and anatomical complexity of these cells hinders the complete understanding of the mechanisms of neurodegeneration and neuroprotection. The present investigations aimed to evaluate the neuroprotective efficacy of a herbal formulation of Nobiletin (NOB) against the toxic insult induced by sodium arsenate (NA) in human neural progenitor cells (hNPCs) derived from human induced pluripotent stem cells (hiPSCs). Prior to the neuroprotective experiments, biologically safe doses of both NOB and NA were ascertained using standard endpoints of cytotoxicity. Thereafter, the hNPCs were exposed to either NOB (50 μM) or NA (50 μM) and co-exposed to biologically safe concentrations of NA (50 μM) with NOB (50 μM) for a period of up to 48 h. NOB treatment restored the morphological damage (neurite damage), the levels of stress granule G3BP1 (Ras-GTPase-activating protein (SH3 domain)-binding protein) and TIA1 (T cell-restricted intracellular antigen), and the expression of neuronal markers (Tuj1, Nestin, MAP2, and PAX6) when compared to NA-exposed cells. A substantial restoration of reactive oxygen species and mitochondrial membrane potential was also witnessed in the co-exposure group (NA + NOB) in comparison to the NA-exposed group. The findings suggest that NOB possesses a significant restorative/protective potential against the NA challenge in hNPCs under experimental conditions and imply that nobiletin may impart a potential therapeutic impact if studied adequately using in vivo studies.

Excitotoxicity is a type of neurodegenerative disorder. It caused by excessive glutamate receptor activation, which leads to neuronal malfunction and fatality. The N-methyl-D-aspartate (NMDA) receptors are found in glutamatergic neurons, and their excessive activation is primarily responsible for excitotoxicity. They are activated by both glutamate binding and postsynaptic depolarization, facilitating Ca2+ entry upon activation. Therefore, they are now widely acknowledged as being essential targets for excitotoxicity issues. Molecular docking and molecular dynamics (MD) simulation analyses have demonstrated that nobiletin efficiently targets the binding pocket of the NMDA receptor protein and exhibits stable dynamic behavior at the binding site. In this study, five potential neuroprotectants, nobiletin, silibinin, ononin, ginkgolide B, and epigallocatechin gallate (EGCG), were screened against the glutamate NMDA receptors in humans via computational methods. An in silico ADMET study was also performed, to predict the pharmacokinetics and toxicity profile for the expression of good drug-like behavior and a non-toxic nature. It was revealed that nobiletin fulfills the criteria for all of the drug-likeness rules (Veber, Lipinski, Ghose, Muegge, and Egan) and has neither PAINS nor structural alerts (Brenks). In conclusion, nobiletin demonstrated a possible promising neuroprotectant activities compared to other selected phytochemicals. Further, it can be evaluated in the laboratory for promising therapeutic approaches for in vitro and in vivo studies.

Chalcones are secondary metabolites belonging to the flavonoid (C6-C3-C6 system) family that are ubiquitous in edible and medicinal plants, and they are bioprecursors of plant flavonoids. Chalcones and their natural derivatives are important intermediates of the flavonoid biosynthetic pathway. Plants containing chalcones have been used in traditional medicines since antiquity. Chalcones are basically α,β-unsaturated ketones that exert great diversity in pharmacological activities such as antioxidant, anticancer, antimicrobial, antiviral, antitubercular, antiplasmodial, antileishmanial, immunosuppressive, anti-inflammatory, and so on. This review provides an insight into the chemistry, biosynthesis, and occurrence of chalcones from natural sources, particularly dietary and medicinal plants. Furthermore, the pharmacological, pharmacokinetics, and toxicological aspects of naturally occurring chalcone derivatives are also discussed herein. In view of having tremendous pharmacological potential, chalcone scaffolds/chalcone derivatives and bioflavonoids after subtle chemical modification could serve as a reliable platform for natural products-based drug discovery toward promising drug lead molecules/drug candidates.

Flavonoids comprise a large group of structurally diverse polyphenolic compounds of plant origin and are abundantly found in human diet such as fruits, vegetables, grains, tea, dairy products, red wine, etc. Major classes of flavonoids include flavonols, flavones, flavanones, flavanols, anthocyanidins, isoflavones, and chalcones. Owing to their potential health benefits and medicinal significance, flavonoids are now considered as an indispensable component in a variety of medicinal, pharmaceutical, nutraceutical, and cosmetic preparations. Moreover, flavonoids play a significant role in preventing cardiovascular diseases (CVDs), which could be mainly due to their antioxidant, antiatherogenic, and antithrombotic effects. Epidemiological and in vitro/in vivo evidence of antioxidant effects supports the cardioprotective function of dietary flavonoids. Further, the inhibition of LDL oxidation and platelet aggregation following regular consumption of food containing flavonoids and moderate consumption of red wine might protect against atherosclerosis and thrombosis. One study suggests that daily intake of 100 mg of flavonoids through the diet may reduce the risk of developing morbidity and mortality due to coronary heart disease (CHD) by approximately 10%. This review summarizes dietary flavonoids with their sources and potential health implications in CVDs including various redox-active cardioprotective (molecular) mechanisms with antioxidant effects. Pharmacokinetic (oral bioavailability, drug metabolism), toxicological, and therapeutic aspects of dietary flavonoids are also addressed herein with future directions for the discovery and development of useful drug candidates/therapeutic molecules.