Green Synthesis of Cerium Oxide Nanoparticles, Characterization, and Their Neuroprotective Effect on Hydrogen Peroxide-Induced Oxidative Injury in Human Neuroblastoma (SH-SY5Y) Cell Line.

Cerium oxide nanoparticles (CeO2NPs) have a broad scale of applications in the biomedical field due to their excellent physicochemical and catalytic properties. The present study aims to synthesize the CeO2NPs from Centella asiatica (C. asiatica) leaf extract, which has been used in Indian traditional medicine for its neuroprotective properties. The CeO2NPs were characterized by ultraviolet-visible, X-ray diffraction, Fourier transform infrared, Raman spectroscopy, scanning electron microscopy- energy dispersive X-ray spectroscopy, and high-resolution transmission electron microscopy. The antioxidant property was evaluated by 2,2-di (4-tert-octyl phenyl)-1-picrylhydrazyl and OH radical assays. The neuroprotective potential was assessed against the oxidative stress (OS) induced by H2O2 in the human neuroblastoma (SH-SY5Y) cell line. CeO2NPs exhibited significant DPPH and OH radical scavenging activity. Our results revealed that CeO2NPs significantly increased H2O2-induced cell viability, decreased lactate dehydrogenase, protein carbonyls, reactive oxygen species generation, apoptosis, and upregulated antioxidant enzyme activity. Our findings suggest that the CeO2NPs protect the SH-SY5Y cells from OS and apoptosis, which could potentially counter OS-related neurodegenerative disorders.

Deciphering the emerging role of phytocompounds: Implications in the management of drug-resistant tuberculosis and ATDs-induced hepatic damage.

Tuberculosis is a disease of poverty, discrimination, and socioeconomic burden. Epidemiological studies suggest that the mortality and incidence of tuberculosis are unacceptably higher worldwide. Genomic mutations in embCAB, embR, katG, inhA, ahpC, rpoB, pncA, rrs, rpsL, gyrA, gyrB, and ethR contribute to drug resistance reducing the susceptibility of Mycobacterium tuberculosis to many antibiotics. Additionally, treating tuberculosis with antibiotics also poses a serious risk of hepatotoxicity in the patient's body. Emerging data on drug-induced liver injury showed that anti-tuberculosis drugs remarkably altered levels of hepatotoxicity biomarkers. The review is an attempt to explore the anti-mycobacterial potential of selected, commonly available, and well-known phytocompounds and extracts of medicinal plants against strains of Mycobacterium tuberculosis. Many studies have demonstrated that phytocompounds such as flavonoids, alkaloids, terpenoids, and phenolic compounds have antibacterial action against Mycobacterium species, inhibiting the bacteria's growth and replication, and sometimes, causing cell death. Phytocompounds act by disrupting bacterial cell walls and membranes, reducing enzyme activity, and interfering with essential metabolic processes. The combination of these processes reduces the overall survivability of the bacteria. Moreover, several phytochemicals have synergistic effects with antibiotics routinely used to treat TB, improving their efficacy and decreasing the risk of resistance development. Interestingly, phytocompounds have been presented to reduce isoniazid- and ethambutol-induced hepatotoxicity by reversing serum levels of AST, ALP, ALT, bilirubin, MDA, urea, creatinine, and albumin to their normal range, leading to attenuation of inflammation and hepatic necrosis. As a result, phytochemicals represent a promising field of research for the development of new TB medicines.

Mucormycosis an added burden to Covid-19 Patients: An in-depth systematic review.

As of 25th July, 2022, global Disease burden of 575,430,244 confirmed cases and over 6,403,511 deaths have been attributed to coronavirus disease 2019 (COVID-19). Co-infections/secondary infections continue to plague patients around the world as result of the co-morbidities like diabetes mellitus, biochemical changes caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) especially significant elevation in free iron levels, immune suppression caused by SARS-CoV-2, and indiscriminate use of systemic corticosteroids for the treatment of severe COVID-19 disease. In such circumstances, opportunistic fungal infections pose significant challenge for COVID-19 disease therapy in patients with other co-morbidities. Although COVID-19-associated Mucormycosis (CAM) has been widely recognized, currently extensive research is being conducted on mucormycosis. It has been widely agreed that patients undergoing corticosteroid therapy are highly susceptible for CAM, henceforth high index of screening and intensive care and management is need of an hour in order to have favorable outcomes in these patients. Diagnosis in such cases is often delayed and eventually the disease progresses quickly which poses added burden to clinician and increases patient load in critical care units of hospitals. A vast perusal of literature indicated that patients with diabetes mellitus and those with other co-morbidities might be highly vulnerable to develop mucormycosis. In the present work, the case series of three patients presented at Chest Disease Hospital Srinagar, Jammu and Kashmir infected with CAM has been described with their epidemiological data in supplementary section. All these cases were found to be affected with co-morbidity of Diabetes Mellitus (DM) and were under corticosteroid therapy. Furthermore, given the significant death rate linked with mucormycosis and the growing understanding of the diseases significance, systematic review of the literature on CAM has been discussed and we have attempted to discuss emerging CAM and related aspects of the disease.

Biofabrication of Silver Nanoparticles (AgNPs) Using Embelin for Effective Therapeutic Management of Lung Cancer.

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.

Repositioning Therapeutics for SARS-CoV-2: Virtual Screening of Plant-based Anti-HIV Compounds as Possible Inhibitors against COVID-19 Viral RdRp.

BACKGROUND: Coronavirus disease 2019 (COVID-19) has caused a global pandemic with a high mortality and morbidity rate worldwide. The COVID-19 vaccines that are currently in development or already approved are expected to provide at least some protection against the emerging variants of the virus, but the mutations may reduce the efficacy of the existing vaccines. Purified phytochemicals from medicinal plants provide a helpful framework for discovering new therapeutic leads as they have long been employed in traditional medicine to treat many disorders. OBJECTIVE: The objectives of the study are to exploit the anti-HIV bioactive compounds against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) through molecular docking studies and to evaluate the Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) properties of potential compounds. METHODS: Molecular docking was performed to study the interaction of ligands with the target sites of RdRp protein (PDB: 6M71) using AutoDock Vina. The ADMET properties of potential compounds were predicted using the pkCSM platform. RESULTS: A total of 151 phytochemicals derived from the medicinal plants with recognized antiviral activity and 18 anti-HIV drugs were virtually screened against COVID-19 viral RdRp to identify putative inhibitors that facilitate the development of potential anti-COVID-19 drug candidates. The computational studies identified 34 compounds and three drugs inhibiting viral RdRp with binding energies ranging from -10.2 to -8.5 kcal/mol. Among them, five compounds, namely Michellamine B, Quercetin 3-O-(2'',6''-digalloyl)-beta-Dgalactopyranoside, Corilagin, Hypericin, and 1,2,3,4,6-Penta-O-galloyl-beta-D-glucose residues, bound efficiently with the binding site of RdRp. Besides, Lopinavir, Maraviroc, and Remdesivir drugs also inhibited SARS-CoV-2 polymerase. In addition, the ADMET properties of top potential compounds were also predicted in comparison to the drugs. CONCLUSION: The present study suggested that these potential drug candidates can be further subjected to in vitro and in vivo studies that may help develop effective anti-COVID-19 drugs.

Eco-Friendly Synthesis of MnO2 Nanorods Using Gmelina arborea Fruit Extract and Its Anticancer Potency Against MCF-7 Breast Cancer Cell Line.

INTRODUCTION: Cancer disease is known due to its unregulated proliferation of cells that have evolved from the body's regular cells. The disease develops as a result of epigenetic and genetic modifications, tumor suppressor gene inactivation, and oncogene activation. The present work describes an environmentally benign approach for the synthesis of manganese oxide nanoparticles (MnO2 NPs) using Gmelina arborea fruit extract (GAE) in an aqueous medium. METHODS: The study evaluated the formation of MnO2 NPs and their anticancer efficacy against MCF-7 breast cancer cell line. RESULTS: The formation of MnO2 NPs was confirmed through powder X-ray diffractometer (XRD), scanning electron microscopy (SEM), transmission electron microscopy (TEM) and high-resolution transmission electron microscopy (HR-TEM). The crystalline nature of as-prepared MnO2 NPs was evident from XRD pattern. The morphology of the material was studied using SEM analysis, which suggested a rod-like nature with an average diameter of 50 nm. Further, the TEM and HR-TEM images confirmed the rod shape of the as-prepared MnO2 NPs with an interplanar distance of 0.271 nm. In addition, the concentric rings from selected area electron diffraction (SAED) analysis show the crystalline nature of the as-prepared material, which further supports the obtained XRD pattern. The anticancer efficacy of MnO2 NPs was evaluated against MCF-7 breast cancer cell line, which showed up to 96% inhibition of the cells at 400 µg/mL concentration. CONCLUSION: Bio-conjugation of MnO2 NPs can provide enough scope for the therapeutic use of Gmelina arborea, assuming appropriate mechanistic evaluations are conducted.

Identification of bioactive molecules from Triphala (Ayurvedic herbal formulation) as potential inhibitors of SARS-CoV-2 main protease (Mpro) through computational investigations.

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.

Plant-Mediated Zinc Oxide Nanoparticles: Advances in the New Millennium towards Understanding Their Therapeutic Role in Biomedical Applications.

Zinc oxide nanoparticles have become one of the most popular metal oxide nanoparticles and recently emerged as a promising potential candidate in the fields of optical, electrical, food packaging, and biomedical applications due to their biocompatibility, low toxicity, and low cost. They have a role in cell apoptosis, as they trigger excessive reactive oxygen species (ROS) formation and release zinc ions (Zn2+) that induce cell death. The zinc oxide nanoparticles synthesized using the plant extracts appear to be simple, safer, sustainable, and more environmentally friendly compared to the physical and chemical routes. These biosynthesized nanoparticles possess strong biological activities and are in use for various biological applications in several industries. Initially, the present review discusses the synthesis and recent advances of zinc oxide nanoparticles from plant sources (such as leaves, stems, bark, roots, rhizomes, fruits, flowers, and seeds) and their biomedical applications (such as antimicrobial, antioxidant, antidiabetic, anticancer, anti-inflammatory, photocatalytic, wound healing, and drug delivery), followed by their mechanisms of action involved in detail. This review also covers the drug delivery application of plant-mediated zinc oxide nanoparticles, focusing on the drug-loading mechanism, stimuli-responsive controlled release, and therapeutic effect. Finally, the future direction of these synthesized zinc oxide nanoparticles' research and applications are discussed.

Natural Products and Nutrients against Different Viral Diseases: Prospects in Prevention and Treatment of SARS-CoV-2.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has caused a global pandemic and is posing a serious challenge to mankind. As per the current scenario, there is an urgent need for antiviral that could act as a protective and therapeutic against SARS-CoV-2. Previous studies have shown that SARS-CoV-2 is much similar to the SARS-CoV bat that occurred in 2002-03. Since it is a zoonotic virus, the exact source is still unknown, but it is believed bats may be the primary reservoir of SARS-CoV-2 through which it has been transferred to humans. In this review, we have tried to summarize some of the approaches that could be effective against SARS-CoV-2. Firstly, plants or plant-based products have been effective against different viral diseases, and secondly, plants or plant-based natural products have the minimum adverse effect. We have also highlighted a few vitamins and minerals that could be beneficial against SARS-CoV-2.

Genotoxic and Cytotoxic Properties of Zinc Oxide Nanoparticles Phyto-Fabricated from the Obscure Morning Glory Plant Ipomoea obscura (L.) Ker Gawl.

The study was undertaken to investigate the antioxidant, genotoxic, and cytotoxic potentialities of phyto-fabricated zinc oxide nanoparticles (ZnO-NPs) from Ipomoea obscura (L.) Ker Gawl. aqueous leaf extract. The UV-visible spectral analysis of the ZnO-NPs showed an absorption peak at 304 nm with a bandgap energy of 3.54 eV, which are characteristics of zinc nanoparticles. Moreover, the particles were of nano-size (~24.26 nm) with 88.11% purity and were agglomerated as observed through Scanning Electron Microscopy (SEM). The phyto-fabricated ZnO-NPs offered radical scavenging activity (RSA) in a dose-dependent manner with an IC50 of 0.45 mg mL-1. In addition, the genotoxicity studies of ZnO-NPs carried out on onion root tips revealed that the particles were able to significantly inhibit the cell division at the mitotic stage with a mitotic index of 39.49%. Further, the cytotoxic studies on HT-29 cells showed that the phyto-fabricated ZnO-NPs could arrest the cell division as early as in the G0/G1 phase (with 92.14%) with 73.14% cells showing early apoptotic symptoms after 24 h of incubation. The results of the study affirm the ability of phyto-fabricated ZnO-NPs from aqueous leaf extract of I. obscura is beneficial in the cytotoxic application.

Optimized Ellagic Acid-Ca Pectinate Floating Beads for Gastroprotection against Indomethacin-Induced Gastric Injury in Rats.

A peptic ulcer is an alimentary tract injury that leads to a mucosal defect reaching the submucosa. This work aimed to optimize and maximize ellagic acid (EA) loading in Ca pectinate floating beads to maximize the release for 24 h. Three factors were selected: Ca pectinate concentration (X1, 1-3 w/v %), EA concentration (X2, 1-3 w/v %) and the dropping time (X3, 10-30 min). The factorial design proposed eight formulations. The optimized EA-Ca pectinate formulation was evaluated for the gastric ulcer index and the oxidative stress parameter determination of gastric mucosa. The results indicated that the optimum EA-Ca pectinate formula significantly improved the gastric ulcer index in comparison with raw EA. The protective effect of the optimized EA-Ca pectinate formula was further indicated by the histopathological features of the stomach. The results of the study indicate that an EA formulation in the form of Ca pectinate beads would be effective for protection against gastric ulcers because of Nonsteroidal anti-inflammatory drugs (NSAID) administration.

Biogenic Gold Nanoparticles as Potent Antibacterial and Antibiofilm Nano-Antibiotics against Pseudomonas aeruginosa.

Abstract: Plant-based synthesis of eco-friendly nanoparticles has widespread applications in many fields, including medicine. Biofilm-a shield for pathogenic microorganisms-once formed, is difficult to destroy with antibiotics, making the pathogen resistant. Here, we synthesized gold nanoparticles (AuNPs) using the stem of an Ayurvedic medicinal plant, Tinospora cordifolia, and studied the action of AuNPs against Pseudomonas aeruginosa PAO1 biofilm. The synthesized AuNPs were characterized by techniques such as ultraviolet-visible spectroscopy, Fourier-transform infrared (FTIR) spectroscopy, energy-dispersive X-ray diffraction, X-ray diffraction, scanning electron microscopy (SEM), and transmission electron microscopy. The AuNPs were spherically shaped with an average size of 16.1 nm. Further, the subminimum inhibitory concentrations (MICs) of AuNPs (50, 100, and 150 µg/mL) greatly affected the biofilm-forming ability of P. aeruginosa, as observed by crystal violet assay and SEM, which showed a decrease in the number of biofilm-forming cells with increasing AuNP concentration. This was further justified by confocal laser scanning microscopy (CLSM), which showed irregularities in the structure of the biofilm at the sub-MIC of AuNPs. Further, the interaction of AuNPs with PAO1 at the highest sub-MIC (150 µg/mL) showed the internalization of the nanoparticles, probably affecting the tendency of PAO1 to colonize on the surface of the nanoparticles. This study suggests that green-synthesized AuNPs can be used as effective nano-antibiotics against biofilm-related infections caused by P. aeruginosa.

Cinnamomum verum Bark Extract Mediated Green Synthesis of ZnO Nanoparticles and Their Antibacterial Potentiality.

Cinnamomum verum plant extract mediated propellant chemistry route was used for the green synthesis of zinc oxide nanoparticles. Prepared samples were confirmed for their nano regime using advanced characterization techniques such as powder X-ray diffraction and microscopic techniques such as scanning electron microscopy and transmission electron microscopy. The energy band gap of the green synthesized zinc oxide (ZnO)-nanoparticles (NPs) were found between 3.25-3.28 eV. Fourier transmission infrared spectroscopy shows the presence of Zn-O bond within the wave number of 500 cm-1. SEM images show the specific agglomeration of particles which was also confirmed by TEM studies. The green synthesized ZnO-NPs inhibited the growth of Escherichia coli and Staphylococcus aureus with a minimum inhibitory concentration (MIC) of 125 µg mL-1 and 62.5 µg mL-1, respectively. The results indicate the prepared ZnO-NPs can be used as a potential antimicrobial agent against harmful pathogens.

Recent Nano-based Therapeutic Intervention of Bioactive Sesquiterpenes: Prospects in Cancer Therapeutics.

In the recent scenario, nanotechnology-based therapeutics intervention has gained tremendous impetus all across the globe. Nano-based pharmacological intervention of various bioactive compounds has been explored on an increasing scale. Sesquiterpenes are major constituents of essential oils (EOs) present in various plant species which possess intriguing therapeutic potentials. However, owing to their poor physicochemical properties; they have pharmacological limitations. Recent advances in nano-based therapeutic interventions offer various avenues to improve their therapeutic applicability. Reckoning with these, the present review collates various nano-based therapeutic intervention of sesquiterpenes with prospective potential against various debilitating diseases especially cancer. In our viewpoint, considering the burgeoning advancement in the field of nanomedicine; in the near future, the clinical applicability of these nano-formulated sesquiterpenes can be foreseen with great enthusiasm.